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Class 9 Social Science Case Study Questions

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If you’re seeking Class 9 Social Science Case Study Questions, you’ve come to the correct spot. Students can use Class 9 Social Science Case Study Questions to help them answer a variety of questions about the Class 9 Social Science case study.

The CBSE Board has included case study questions in Class 9 Social Science examination pattern. As a result, it becomes an indispensable study tool.

The need for a student-friendly app to explain and facilitate the understanding of the social sciences subject has been felt for a long. Especially for students who do not have a strong foundation in Class 9 Social Science. With myCBSEguide , class 9 social science students now have a place where they can find resources that are student-friendly, interesting and easy to understand.

Class 9 Social Science Case Study questions are intended to assess student’s abilities to apply their learning to practical scenarios. You’ll need to employ your critical thinking and problem-solving skills to come up with the best solution. Class 9 Social Science case study questions are designed to test your knowledge and help you improve your skills.

Class 9 Social Science Case Study Questions Samples

myCBSEguide has identified the essential themes connected to CBSE case study questions for Class 9 Social Science that every student should be aware of following a comprehensive examination of CBSE Sample Papers and Marking Scheme. Students in Class 9 Social Science will benefit from this information in understanding the changes in the Class 9 Social Science. For a better understanding and analysis, students should refer to the example of Class 9 Social Science case study questions attached below:

Class 9 Social Science Case Study Question 1

Read the source given below and answer the questions that follow: On the morning of 14 July 1789, the city of Paris was in a state of alarm. The king had commanded troops to move into the city. Rumours spread that he would soon order the army to open fire upon the citizens. Some 7,000 men and women gathered in front of the town hall and decided to form a peoples’ militia. They broke into a number of government buildings in search of arms. Finally, a group of several hundred people marched towards the eastern part of the city and stormed the fortress-prison, the Bastille, where they hoped to find hoarded ammunition. In the armed fight that followed, the commander of the Bastille was killed and the prisoners released – though there were only seven of them. Yet the Bastille was hated by all because it stood for the despotic power of the king. The fortress was demolished and its stone fragments were sold in the markets to all those who wished to keep a souvenir of its destruction. The days that followed saw more rioting both in Paris and the countryside. Most people were protesting against the high price of bread. Much later, when historians looked back upon this time, they saw it as the beginning of a chain of events that ultimately led to the execution of the king in France, though most people at the time did not anticipate this outcome. Answer the following MCQs by choosing the most appropriate option:

On 14th July, 1789 the people of the ________ estate attacked the Bastille prison and freed all the prisoners signalling the start of the _________.

• first, civil war
• fourth, Russian war
• second, movement
• third, revolution

Which of the following statement is incorrect?

• The Bastille was the fortress-prison.
• The Bastille stood for the democratic power of the king.
• On the morning of 14 July 1789, the people of Paris stormed Bastille
• All are correct

In the question given below, there are two statements marked as Assertion (A) and Reason (R). Read the statements and chose the correct option: Assertion (A): The people of France storm the Bastille. Reason (R): They were hopeful to find King Louis XIV and commander of the Bastille there.

• Both A and R are correct and R is the correct explanation of A.
• Both A and R are correct but R is not the correct explanation of A.
• A is correct but R is wrong.
• Both A and R are wrong.

What was the immediate cause of rioting in Paris?

• Atrocities by the commander
• The high price of bread
• The killing of women and children
• All of these

Answer Key:

• (d) third, revolution
• (b) The Bastille stood for the democratic power of the king. [Explanation: The Bastille stood for the despotic power of the king.]
• (c) A is correct but R is wrong. [Explanation: The people of France stormed the fortress-prison, the Bastille because they were hopeful to find hoarded ammunition there.]
• (b) high price of bread

Class 9Social Science Case Study Question 2

Read the extracts and answer the question that follows:

The Himalayas, geologically young and structurally fold mountains stretch over the Himalayas northern borders of India. These mountain ranges run in a west-east direction from the Indus to the Brahmaputra. The Himalayas represent the loftiest and one of the most rugged mountain barriers of the world. They form an arc, which covers a distance of about 2,400 Km. Their width varies from 400 Km in Kashmir to 150 Km in Arunachal Pradesh. The altitudinal variations are greater in the eastern half than those in the western half. The Himalaya consists of three parallel ranges in its longitudinal extent. A number of valleys lie between these ranges. The northern most range is known as the Great or Inner Himalayas. It is the most continuous range consisting of the loftiest peaks with an average height of 6,000 metres. It contains all the prominent Himalayan peaks.

The folds of Great Himalayas are asymmetrical in nature. The core of this part of Himalayas is composed of granite. It is perennially snow bound, and a number of glaciers descend from this range.

• The Great or Inner Himalayas is also known as?
• Give two features of the folds of Great Himalayas.
• Give two features of the Inner Himalayas.
• The Great or Inner Himalayas is also known as the ‘Himadri’.
• (Any two relevant points)
• The folds of Great Himalayas are asymmetrical in nature.
• The core of this part of Himalayas is composed of granite.
• It is perennially snow bound, and a number of glaciers descend from this range.
• Features of the Inner Himalayas:
• It is the most continuous range consisting of the loftiest peaks with an average height of 6,000 metres.
• It contains all the prominent Himalayan peaks.  

Class 9 Social Science Case Study Question 3

Read the source given below and answer the questions that follow: In Pakistan, General Pervez Musharraf led a military coup in October 1999. He overthrew a democratically elected government and declared himself the ‘Chief Executive’ of the country. Later he changed his designation to President and in 2002 held a referendum in the country that granted him a five-year extension. Pakistani media, human rights organisations and democracy activists said that the referendum was based on malpractices and fraud. In August 2002 he issued a ‘Legal Framework Order’ that amended the Constitution of Pakistan. According to this Order, the President can dismiss the national and provincial assemblies. The work of the civilian cabinet is supervised by a National Security Council which is dominated by military officers. After passing this law, elections were held to the national and provincial assemblies. So Pakistan has had elections, elected representatives have some powers. But the final power rested with military officers and General Musharraf himself. Clearly, there are many reasons why Pakistan under General Musharraf should not be called a democracy. People may have elected their representatives to the national and provincial assemblies but those elected representatives were not really the rulers. They cannot take the final decisions. The power to take final decision rested with army officials and with General Musharraf, and none of them were elected by the people. This happens in many dictatorships and monarchies. They formally have an elected parliament and government but the real power is with those who are not elected. In a few countries, the real power was with some external powers and not with locally elected representatives. This cannot be called people’s rule. Answer the following MCQs by choosing the most appropriate option:

What is the meaning of Referendum?

• Direct vote in which the entire electorate is asked to either accept or reject a particular proposal
• A form of government in which the rulers are elected by the people
• A system where the majority or elected representatives are allowed to take decisions on behalf of all the people

In the question given below, there are two statements marked as Assertion (A) and Reason (R). Read the statements and chose the correct option: Assertion (A): Pakistan not considered a democratic country even after having elections Reason (R): Despite elections to the national and provincial assemblies, the final powers rested with General Musharraf and military officers.

• Both A and R are true and R is the correct explanation of A.
• Both A and R are true but R is not the correct explanation of A.
• A is wrong but R is correct.

After the passage of the ________, elections were held to the national and state assemblies.

• Military rule
• Legal Framework Order
• Both (b) and (c)

Does the given source explain the significance of which feature of democracy?

• Democracy must be based on a free and fair election
• In a democracy, the final decision-making power must rest with those elected by the people
• In a democracy, each adult citizen must have one vote
• Democratic government rules within limits set by constitutional law and citizens’ rights
• (a) Direct vote in which the entire electorate is asked to either accept or reject a particular proposal
• (a) Both A and R are true and R is the correct explanation of A.
• (c) Legal Framework Order
• (b) In a democracy, the final decision-making power must rest with those elected by the people

Steps to Master Class 9 Social Science Case Study Questions

Class 9 Social Science case study questions can be daunting, but there are some strategies you can use to ace them. There is no one-size-fits-all answer to Class 9 social science case study questions. The best way to solve a social science case study will vary depending on the specific case in question. However, there are some general tips that can be followed in order to improve your chances of success while answering class 9 social science case study questions.

• First, make sure to read the question carefully and understand what is being asked. It is often helpful to re-read the question after gathering all of your information.
• Next, organize your thoughts and create an outline of your answer. This will help you to stay on track and include all relevant information.
• Finally, write your answer in a clear and concise manner.

Class 9 Social Science Content Structure

Class 9 social science content is divided into four parts: History, Geography, Economics and Political Science. Each part is further divided into smaller themes/chapters.

Each of these topics given in Class 9 Social Science is important in its own right, and together they provide a comprehensive overview that affect our world today. The content is structured in such a way as to provide Class 9 Social Science students with a broad understanding of each issue, while also allowing them to focus on specific areas that are of particular interest to Class 9 Social Science students.

Class 9 Social Science COURSE CONTENT 

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Chapter 1 Ideological Basis of Pakistan 9th Pak Study

9th class pak study chapter no.1 ideological basis of pakistan urdu and english notes.

Definition of Ideology : Ideology refers to a set of beliefs, values, ideas, and principles that form the foundation of a political, social, or economic system. It is a comprehensive worldview that guides individuals or groups in understanding and interpreting the world around them. Ideologies shape people’s perspectives on issues, influence their behavior, and provide a framework for decision-making.

• Chapter No.1 Introduction to Biology
• Chapter No. 2 Solving a Biological Problem
• Chapter No.3 Biodiversity
• Chapter No.4 Cells and Tissues
• Chapter No.5 Cell Cycle

Sources of Ideology : a. Historical Context: Historical events, revolutions, and social movements often play a crucial role in shaping ideologies. For example, the French Revolution gave rise to the ideology of liberalism, advocating for individual rights and freedoms.

b. Philosophical Thought : Ideologies are often influenced by philosophical thinkers who propose new ideas and concepts about society and governance. Thinkers like John Locke and Karl Marx have significantly impacted the development of liberal and socialist ideologies, respectively.

c. Religious Beliefs : Religion can also be a significant source of ideology. In some cases, religious beliefs may influence political ideologies, shaping policies and governance according to religious principles.

d. Economic Factors : Economic conditions and theories can shape ideologies related to capitalism, socialism, or communism. The distribution of wealth and resources often becomes a focal point for ideological debates.

e. Cultural Traditions : Cultural values and traditions play a role in shaping ideologies specific to certain societies or regions. They influence how people perceive their identity and interact with others.

Significance of Ideology : a. Political Decision-Making : Ideologies provide a framework for politicians and policymakers to make decisions and formulate policies based on their underlying beliefs. Political parties often align with specific ideologies, which guide their approach to governance.

b. Social Movements : Ideologies play a crucial role in mobilizing people for social and political causes. Movements advocating for civil rights, women’s rights, environmental protection, and more are often driven by ideological beliefs.

c. National Identity : Ideologies contribute to shaping a nation’s identity and unity. They provide a sense of shared values and aspirations, strengthening the social fabric of a country.

d. Conflict and Cooperation : Ideological differences can lead to conflicts and rivalries between nations or groups with opposing beliefs. At the same time, shared ideologies can foster cooperation and alliances.

e. Policy Debates: Ideological differences often fuel debates on various issues, ranging from economic policies to social reforms. Understanding ideological perspectives is crucial in comprehending policy disagreements.

f. Individual Behavior : Ideologies influence individual behavior and choices. They shape how people vote, participate in civic activities, and engage with society.

Overall, ideology is a fundamental aspect of human societies, influencing governance, culture, and individual beliefs. Understanding the sources and significance of ideology is essential for comprehending the dynamics of political, social, and economic systems.

The importance of ideology lies in its ability to provide a guiding framework, a set of principles, and a shared vision for individuals and societies. Ideology shapes the way people perceive the world, understand their roles and responsibilities, and make decisions about various aspects of life. Here are some key reasons highlighting the importance of ideology:

Identity and Belonging : Ideology provides a sense of identity and belonging to individuals and groups. It helps people define who they are, what they stand for, and what they aspire to achieve. A shared ideology creates a sense of unity and community among like-minded individuals, fostering a strong sense of belonging.

Foundation for Governance : In political systems, ideology serves as the foundation for governance. It shapes the policies, laws, and institutions that govern a nation. For example, democracies may be guided by the ideology of liberalism, emphasizing individual rights and freedoms, while socialist states may prioritize principles of equality and collective welfare.

Vision for the Future : Ideologies often present a vision for the future. They articulate a desired state of society, economy, or governance that people can work towards. This vision helps mobilize individuals and communities to strive for positive change and progress.

Decision Making : Individuals and policymakers often use ideology to make decisions. It provides a set of values and principles against which choices are evaluated. Ideology helps prioritize goals and determine the best course of action based on core beliefs.

Social Mobilization : Ideological beliefs can mobilize large groups of people for collective action. Social and political movements are often driven by a shared ideology, rallying people around a common cause, such as civil rights, environmental protection, or social justice.

Conflict Resolution : In times of conflict, ideology can play a crucial role in finding common ground and resolving disputes. Shared values and principles can serve as a basis for negotiations and compromise between opposing parties.

Cultural Preservation : Ideology plays a role in preserving cultural heritage and traditions. It can be a force in safeguarding cultural practices, languages, and historical narratives, fostering a sense of continuity and identity.

Ethical Framework : Ideology provides an ethical framework for individuals and societies to distinguish between right and wrong. It helps establish moral standards and principles that guide behavior and decision-making.

National Unity : In multicultural and diverse societies, ideology can be a unifying force. It helps build a common national identity and a shared sense of purpose, fostering social cohesion and solidarity.

Overall, ideology shapes attitudes, behavior, and institutions in society. It is a powerful force that influences the direction of a nation and the aspirations of its people. The importance of ideology lies in its role as a driving force for collective action, social progress, and the shaping of a nation’s destiny.

The Ideology of Pakistan refers to the set of principles, beliefs, and values that form the foundation of the nation of Pakistan. It encompasses the core ideas that were articulated during the creation of Pakistan and continue to shape its identity, governance, and national outlook. The Ideology of Pakistan is based on the idea that Muslims of the Indian subcontinent are a separate nation with distinct cultural, religious, and historical backgrounds, and they deserve a separate homeland.

Key meanings and components of the Ideology of Pakistan are:

Two-Nation Theory : The central premise of the Ideology of Pakistan is the Two-Nation Theory, which asserts that Muslims and Hindus are two separate nations in the Indian subcontinent. According to this theory, Muslims have their own distinct identity and cannot coexist with Hindus in a unified India. Therefore, they need a separate homeland to safeguard their rights and interests.

Creation of Pakistan : The Ideology of Pakistan led to the demand for a separate Muslim state, which resulted in the creation of Pakistan on August 14, 1947. The country was carved out of British India, with two wings, East Pakistan (now Bangladesh) and West Pakistan (now Pakistan), separated by India.

Islam as a Unifying Force : The Ideology of Pakistan emphasizes Islam as a unifying force that binds the diverse ethnic and linguistic groups of the country together. It envisages Pakistan as a state that upholds Islamic principles, promotes the welfare of its Muslim citizens, and provides an environment for practicing their faith freely.

Equal Rights and Protection for Minorities : While Islam holds a central place in the Ideology of Pakistan, it also upholds the principles of equal rights, protection, and freedom for religious minorities. The vision of Pakistan’s founding leaders, such as Muhammad Ali Jinnah, was to create a state where all citizens, regardless of their religion, would enjoy equal rights and opportunities.

Democracy and Social Justice : The Ideology of Pakistan envisions a democratic and just society where the rule of law prevails, and social and economic justice is ensured for all citizens. It rejects any form of discrimination and exploitation.

Independence and Sovereignty : The Ideology of Pakistan upholds the idea of national independence and sovereignty. It emphasizes the importance of a strong and self-reliant Pakistan that can protect its interests on the global stage.

Unity and Integration : The Ideology of Pakistan promotes the unity and integration of all provinces and regions. It envisions a strong sense of national identity that transcends regional and ethnic differences.

Civic Nationalism : The Ideology of Pakistan is based on the concept of civic nationalism, where citizenship and allegiance to the state are defined by adherence to its values and principles, rather than ethnicity or language.

The Ideology of Pakistan is enshrined in the country’s Constitution and is upheld by its institutions. It serves as a guiding framework for Pakistan’s governance, foreign policy, and national identity, shaping the nation’s trajectory and aspirations.

The Ideology of Pakistan is deeply rooted in the principles of Islam, the vision of Muslim reformers, and the socio-cultural aspects of Muslim India. It reflects the aspirations of the Muslims of the Indian subcontinent for a separate homeland where they could practice their faith freely and preserve their distinct cultural identity. Let’s explore how these elements contributed to the formation of the Ideology of Pakistan:

Basic Values of Islam : Islam is at the core of the Ideology of Pakistan. The belief in the oneness of Allah, the finality of Prophet Muhammad’s (PBUH) prophethood, and the adherence to the teachings of the Quran and Sunnah form the foundation of Pakistan’s identity. The demand for a separate Muslim state was based on the principle that Muslims, as a separate religious community, should have the freedom to live according to Islamic principles without any fear of religious discrimination.

Muslim Reformers : Throughout history, Muslim reformers and intellectuals played a significant role in shaping the collective consciousness of the Muslim community in India. Scholars like Sir Syed Ahmad Khan, Allama Iqbal, and Muhammad Ali Jinnah emphasized the importance of education, unity, and political representation for Muslims. Sir Syed Ahmad Khan advocated for modern education and coexistence with the British, while Allama Iqbal envisioned a separate Muslim state where Muslims could practice their faith and culture freely. Muhammad Ali Jinnah, the founding leader of Pakistan, translated these ideas into a political movement and successfully negotiated the creation of Pakistan.

Socio-Cultural Aspects of Muslim India : Muslims in India had a distinct socio-cultural identity with a rich history and heritage. They had their own language (Urdu), art, literature, and traditions that set them apart from other communities. However, as the Indian National Congress became dominated by the Hindu majority, Muslims felt a growing sense of alienation and concern about their future in an independent India. The demand for Pakistan emerged as a response to these concerns and aimed to protect the cultural and religious rights of the Muslim minority.

Two-Nation Theory : The Two-Nation Theory, formulated by Muslim leaders like Sir Syed Ahmad Khan and further emphasized by Allama Iqbal, played a crucial role in the development of the Ideology of Pakistan. It posited that Hindus and Muslims were two separate nations with distinct religious, cultural, and historical backgrounds. This theory provided the intellectual basis for the demand for a separate Muslim state.

Struggle for Political Rights : The Ideology of Pakistan was also a response to the political marginalization of Muslims in British India. Muslims demanded adequate political representation to safeguard their interests and protect their cultural and religious rights. The Lahore Resolution of 1940, passed by the All India Muslim League, demanded the creation of an independent Muslim state where Muslims could shape their destiny according to their values and beliefs.

In conclusion, the Ideology of Pakistan is a multifaceted concept that draws its strength from the principles of Islam, the ideas of Muslim reformers, and the socio-cultural aspects of Muslim India. It represents the aspirations of the Muslims of the Indian subcontinent for a separate homeland where they could preserve their distinct identity and practice their faith freely. The establishment of Pakistan in 1947 marked the realization of this ideology and the beginning of a new chapter in the history of South Asia.

Elements of Ideology of Pakistan

The Ideology of Pakistan encompasses several key elements that reflect the fundamental beliefs and principles on which the nation was founded. These elements include:

Beliefs : The Ideology of Pakistan is grounded in the belief in the oneness of Allah and the principles of Islam. Muslims in Pakistan consider Islam as the guiding force for their personal and collective lives. The Quran and Sunnah of the Prophet Muhammad (PBUH) serve as the primary sources of guidance, morality, and ethics.

Pillars of Islam : The five pillars of Islam, which are fundamental acts of worship and devotion, hold great significance in the Ideology of Pakistan. These pillars are: a. Shahada (Declaration of Faith) : Affirming the belief in the oneness of Allah and the Prophethood of Muhammad (PBUH). b. Salat (Prayer) : Observing the five daily prayers as a means of spiritual connection with Allah. c. Zakat (Charity) : Giving a portion of one’s wealth to support the less fortunate and promote social justice. d. Sawm (Fasting) : Observing the fast during the month of Ramadan to purify the soul and attain God-consciousness. e. Hajj (Pilgrimage) : Undertaking the pilgrimage to the holy city of Mecca, if financially and physically able, as a symbol of unity and equality among Muslims.

Rule of Law : The Ideology of Pakistan emphasizes the rule of law, which means that all individuals, regardless of their social status, are subject to the same laws and regulations. It upholds the principles of justice, accountability, and equal treatment under the law. This ensures that no one is above the law and that the legal system operates fairly and impartially.

Equality and Brotherhood : The Ideology of Pakistan advocates for equality and brotherhood among its citizens. It rejects any form of discrimination based on race, religion, ethnicity, or social background. All Pakistanis are considered equal before the law and have the right to enjoy the same rights and opportunities.

Justice and Equity : Justice is a core principle of the Ideology of Pakistan. It demands that the state and its institutions ensure a just and equitable society where individuals are treated fairly, and their rights are protected. This includes access to education, healthcare, employment, and basic needs, regardless of socioeconomic status.

In summary, the Ideology of Pakistan is built upon the beliefs of Islam, the observance of its pillars, the promotion of the rule of law, the cultivation of equality and brotherhood, and the pursuit of justice and equity. These elements form the moral and ethical framework on which the nation seeks to build a harmonious and prosperous society that upholds the principles of Islam and fosters a sense of unity and compassion among its citizens.

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• CBSE Notes For Class 9
• Class 9 Social Science Notes
• Class 9 Political Science Notes
• Chapter 1 What Is Democracy Why Democracy

CBSE Notes Class 9 Political Science Chapter 1-What is Democracy? Why Democracy?

What is a democracy? What are its features? Chapter 1 from CBSE Class 9 Political Science textbook, ‘Democratic Politics- I’, builds on a simple definition of democracy. The aim of the book is to help students understand clearly the bare minimum features of a democratic form of government. After going through this chapter, you will be able to find the difference between a democratic form of government and a non-democratic government. Democracy is the most prevalent form of government in the world today, and it is expanding to more countries. But why is it so? What makes it better than other forms of government? Students can just browse through these CBSE Notes Class 9 Political Science Chapter 1 – ‘What is Democracy? Why Democracy?’ and understand these concepts thoroughly.

Click on the downloadable link to access the CBSE Class 9 Social Science Notes of Political Science Chapter 1 below in this article.

• Chapter 2 Constitutional Design
• Chapter 3 Electoral Politics
• Chapter 4 Working Of Institutions
• Chapter 5 Democratic Rights

CBSE Notes Class 9 Political Science Chapter 1-What Is Democracy? Why Democracy?

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What Is Democracy? Why Democracy?

Definition of Democracy

Democracy is a form of government in which the rulers are elected by the people. One chief factor common to all democracies is that the government is chosen by the people. It also helps students to demarcate between democratic and non-democratic governments. For the non-democratic government, take the example of Myanmar, where rulers were not elected by the people. Those who were in charge of the country’s army took over as rulers, and people had no say in this decision. Dictators like Pinochet (Chile) are not elected by the people. This also applies to monarchies.

Features of Democracy

The simple definition of democracy gives rise to various questions, which are given below:

• Who are the rulers in this definition?
• What kind of election constitutes a democratic election?
• Who are the people who can elect the rulers or get elected as rulers?
• Finally, what form of government is a democracy?

Major Decisions by Elected Leaders

Some countries like Pakistan do not follow this rule. In Pakistan, General Pervez Musharraf led a military coup in October 1999. He overthrew the democratically elected government and went on to become the President of the country. In 2002, he also held a referendum in the country that granted him a five-year extension. Meanwhile, after the passing of this ‘Legal Framework Order’, elections were held in the national and provincial assemblies, and elected representatives were granted some powers. But the final power rested with military officers and General Musharraf himself. Hence, we can conclude it was not a democratic country. The same thing happens in many dictatorships and monarchies. Thus, we can conclude that in a democracy, the final decision-making power must rest with those elected by the people.

Free and Fair Electoral Competition

In China, elections are held after every five years to elect the country’s parliament, called Quanguo Renmin Daibiao Dahui (National People’s Congress). Before contesting elections, a candidate needs the approval of the Chinese Communist Party. The government is always formed by the Communist Party. Alternatively, since its independence in 1930, Mexico has held elections after every six years to elect its President. But until 2000, every election was won by a party called PRI (Institutional Revolutionary Party). Should we consider the elections described above as examples of people electing their rulers? Reading these examples, we get a sense that we cannot. Democracy must be based on a free and fair election where those currently in power have a fair chance of losing.

One Person, One Vote, One Value 

Democracy is based on a fundamental principle of political equality. However, there are many instances of denial of the equal right to vote. Until 2015, in Saudi Arabia, women did not have the right to vote. Estonia has made its citizenship rules in such a way that people belonging to the Russian minority found it difficult to get the right to vote. In Fiji, the electoral system is such that the vote of an indigenous Fiji has more value than that of an Indian-Fijian. Definitely not a democratic government. The feature of democracy this highlights is that in a democracy, each adult citizen must have one vote, and in turn, each vote must have one value.

Rule of Law and Respect for Rights

Zimbabwe attained independence from White minority rule in 1980, and since then, the country has been ruled by the party that led the freedom struggle, ZANU-PF. Its leader,

Robert Mugabe has ruled the country since independence. Even if elections were held regularly, it was always won by ZANU-PF. President Mugabe was popular but also used unfair practices in elections. There was a law that limited the right to criticise the President. Television and radio were controlled by the government and gave only the ruling party’s version. There were independent newspapers, but the government harassed those journalists who went against it and so on. Not a democratic government. Democratic government rules within limits set by constitutional law and citizens’ rights.

Hence, we can deduce that democracy is a form of government in which:

• Rulers elected by the people take all the major decisions
• Elections offer a choice and fair opportunity to the people to change the current rulers
• This choice and opportunity is available to all people on an equal basis
• The exercise of this choice leads to a government limited by basic rules of the constitution and citizens’ rights

Why Democracy?

Cons of Democracy

• Leaders keep changing in a democracy leading to instability.
• Democracy is all about political competition and power play, leaving no scope for morality.
• Many people have to be consulted in a democracy, which leads to delays.
• Elected leaders do not know the best interest of the people, resulting in bad decisions.
• Democracy leads to corruption since it is based on electoral competition.
• Ordinary people don’t know what is good for them; they should not decide anything.

From these arguments, we can see that democracy of the kind we see may not be the ideal form of government. However, we will see if democracy is better than other forms of government that are there for us to choose from.

Arguments in Favour of Democracy

A democratic government is a better government because it is a more accountable form of government: Take the example of the famines of 1958-1961 in India and China. While China was hit badly, India did not fare as badly, despite its economic condition. The reason for this could be that India responded to the food scarcity in a way that the Chinese government did not. Here, we see that democracy is better than any other form of government in responding to the needs of the people.

Democracy improves the quality of decision-making: Democracy is based on consultation and discussion. A democratic decision always involves many people, discussions and meetings, and they are able to point out possible mistakes in any decision. This may take time. However, the advantage of taking time over important decisions is that it reduces the chances of rash or irresponsible decisions.

Democracy provides a method to deal with differences and conflicts: In any society, people are bound to have differences of opinions and interests. These differences are particularly more in a country like ours, with amazing social diversity. People belong to different regions, speak different languages, practise different religions and have different castes. The preferences of one group can clash with those of other groups. How do we resolve such a conflict? Democracy provides the only peaceful solution to this problem. In a democracy, no one is a permanent winner or loser. Different groups can live with one another peacefully.

Democracy enhances the dignity of citizens: Democracy is based on the principle of political equality. It recognises that the poorest and the least educated have the same status as the rich and the educated.

Democracy is better than other forms of government because it allows us to correct our own mistakes: Even if no government can guarantee that no mistakes will be made, in a democracy, one can be sure that it will not be hidden for too long. It makes space for public discussion on these mistakes. There is also room for correction. Rulers have to change their decisions, or they could themselves be changed.

Thus, we can correctly infer that while democracy may not be the solution to all problems, it is still clearly better than any other alternative.

Broader Meanings of Democracy

In this chapter, the meaning of democracy is discussed in a descriptive sense. Students get to learn about democracy as a form of government, thus helping them to identify a clear set of minimal features that democracy requires. The common form adopted by democracy is representative democracy. In democratic countries, all people do not rule. A majority is allowed to take decisions on behalf of all the people through their elected representatives. This has become necessary for the reasons given below:

• Modern democracies involve such a large number of people that it is physically impossible for them to sit together and take a collective decision.
• Even if they could, the citizen does not have the time, the desire or the skills to take part in all the decisions.

Democracy, as a principle, can go beyond the government and can be applied to any sphere of life. People use the word democracy not to describe any existing government but to set up an ideal standard that all democracies must aim to become. However, if the ideals of democracy are considered, then no country in the world is correctly democratic. Still, having an understanding of democracy as an ideal will explain why to value democracy. It enables people to judge an existing democracy and identify its weaknesses. It also helps to distinguish between a minimal democracy and a good democracy. The most common form of democracy in today’s world is being ruled by people’s elected representatives. However, for a small community, there can be other ways of making democratic decisions. All people can sit together and make decisions directly. This is how the Gram Sabha should work in a village.

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Frequently Asked Questions on CBSE Class 9 Political Science Notes Chapter 1 What Is Democracy, Why Democracy?

Why should we have a democracy.

1. Equality and freedom of all actions 2. Voting leads to the proper selection of government officials 3. Deal with conflicts 4. Enhances women empowerment

Where is Zimbabwe located?

Zimbabwe, a landlocked country in South East Africa, is separated from Zambia by the Zambezi River.

What is a ‘Legal Framework Order’?

The Legal Framework Order refers to presidential decrees issued during military rule in Pakistan in 1970 and 2002 over the organisation of elections.

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Table of contents.

Describe basic difference between the foundation of Pakistan and other independent countries.

Pakistan came into existence on 14 th of August, 1947 during the twentieth century, many nations got freedom, and many free independent states emerged on the map of the world. Pakistan is also one of those countries, but the foundation of Pakistan was altogether unique and unprecedented.

The basis of the Foundation of other independent countries:

          Most of the countries got freedom on a racial, linguistic or territorial basis. Pakistan is the only country which came into being based on a strong ideology.

The basis of the Foundation of Pakistan:

        The basis of the ideology of Pakistan lies in the religion of Islam which guides the Muslims in every sphere of life. Islamic way of living encompasses all aspects of human life. It has a basic principle concerning social, moral, political, religious and economic fields. The Islamic system is based on the Holy Quran. Die Sunnah of the Hazrat Muhammad (PBUH) and the Ahaadith. This very system was declared the basis of Pakistan.

Describe the meanings and definition of the Ideology of Pakistan.

Meanings of the Ideology of Pakistan:

        The Muslims ruled the Sub-continent for centuries. They continued living freely according to the teachings of their religion. The establishment of British rule caused harm to the free status of Muslims and Islam. During their reign, the Muslims were oppressed. When the British rule was near its end, it was evident that the Hindu majority government will be formed in the Sub-continent. It was feared that after getting rid of the temporary slavery of the British, the Muslims will become permanent slaves of the Hindus.

Efforts of Muslim Dignities:

        Many Muslim dignitaries including Sir Syed Ahmad Khan. Quaid-e-Azam Muhammad Ali Jinnah (Rahmatullah) and Allama Muhammad Iqbal (Rahmatullah) started their efforts for the security of dignity and freedom of the Muslim community in the Subcontinent. As a result of these dignified personalities. Pakistan came into being.

Definition of the Ideology of Pakistan:

        If we keep the definition of the ideology in view, we can easily understand the meanings of the ideology of Pakistan.

• The ideology of Pakistan is the name of creating a society based on the principles of the Quran and Sunnah
• The ideology of Pakistan is the name of practising the principles of Islam. It is also the name of thinking to get the laboratory to test three principles.
• The ideology of Pakistan is the name of steps that were taken for the security of the political, social, cultural and economic values of the Muslims.
• The ideology of Pakistan is the name of practical efforts for establishing the rule of Islam and strengthening the unity among the Muslims, without losing the national (Mile) identity.
• The ideology of Pakistan is the name of a welfare state where the welfare of the people is considered.

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CBSE What is Democracy? Why Democracy? Class 9 Civics Chapter 1 Notes PDF

• Revision Notes
• Social Science: Political Science
• Chapter 1 What Is Democracy? Why Democracy?

What is Democracy? Why Democracy? Class 9 Notes FREE PDF Download

Democratic Politics-I, Chapter 1 of the CBSE Class 9 Civics Chapter 1 Notes PDF , deals with the basic notion of democracy as well as its characteristics. Civics Class 9 Chapter 1 Notes PDF available on Vedantu's official website contains all of the key themes mentioned in the chapter. Experts handpicked the revision notes to assist students in developing a precise better knowledge of democracy and its elements. Vedantu provides the most detailed and exact review in Class 9th Civics Chapter 1 Notes.

When generating Civics Class 9 Chapter 1 Notes, the CBSE board's criteria are taken into account. As a result, folks can consult them and benefit from good exam scores. Get the free printable PDF version of the Chapter 1 Civics Class 9 Notes and begin learning whenever and wherever you choose.

Download CBSE Class 9 Political Science Revision Notes 2024-25 PDF

Also, check CBSE Class 9 Political Science revision notes for All chapters along with the Class 9 Civics Chapter 1 Notes PDF:

Access Class 9 Civics Chapter 1 Notes PDF: What is Democracy? Why Democracy?

Definition of democracy.

It is defined as a form of government where rulers are elected by the choice of people.

So, the difference between democratic and non-democratic governments is that the power of electing their representative is in people’s hands.

Examples of Non-Democratic Governments

In Myanmar, the army controller becomes the ruler and people over there have no role to play in electing their representative.

In Saudi Arabia, the representatives are from royal families, this is the base on which they qualify to become kings. Here also, people have no role to play in making decisions.

Features of Democracy

Here are few questions which is necessary to be answered for a true democracy:

Which type of people are going to be elected as rulers and what kind of decisions need to be taken by non-elected officials?

In which circumstances an election is to be considered democratic?

What includes in the elector’s population and whether they are equal or have some exceptions?

What is the form of a democratic government? Also, state what are the limitations and freedoms of a decision making by the representative who is elected?

How much is necessary for a democracy to respect the rights of a citizen?

Major Decision by the Elected Leaders

Pakistani General Pervez Musharraf, in October 1999 led the military and overthrew a democratic government and declared himself the ‘Chief Executive’.

In the year 2002, he changed his designation to President and declared himself an additional 5 years.

In the year August 2002, he passed the ‘Legal Framework Order’ which stated that the President can dismiss the national and provincial assemblies.

After elections, elected candidates vested some powers, the final power rested with military officers and General Musharraf. It shows that it is not a democratic country.

In the USSR in communist Poland and the US in contemporary Iraq, power lied with external instead of elected locals. Whereas in democracy, the final power lies with those which are elected by the people.

Free and Fair Electoral Competition

In China, to elect members for the country’s parliament which is called Quanguo Renmin Daibiao Dahui (National People’s Congress), elections are held every 5 years.

Candidate needs to be a member of the Chinese Communist Party or 8 of its allies to contest elections in 2002-03.

The communist party used to form the government.

Since independence, 1930, Mexico presidential elections have been held every 6 years. Until 2000 each and  every election was won by PRI (Institutional Revolutionary Party).

A fair and free electoral competition where the existing ruling party has a fair chance to lose is an aspect of democracy.

Examples of Democracy are – India and the United States etc.

One Person, One Vote, One Value

Political equality is the basis of democracy. 

In a few instances where equal rights are denied have been observed.

Women had no right to vote until 2015, in Saudi Arabia.

In Estonia, citizen rules made it very much difficult for people from Russian minorities to gain the right to vote.

Fiji’s electoral system gave more value to indigenous Fiji than Indian-Fijian.

These are some examples which contradict the basis of democracy where an adult citizen must have one vote with equal value.

Rule of Law and Respect for Rights

In the year 1980, Zimbabwe gained independence. The leader Robert Mugabe of the ZANU-PF party, which led for the freedom struggle ruled the country.

President Mugabe used malpractices in elections so that ZANU-PF always won.

Only the verdicts of the ruling party were presented by the television and radios since a law existed that restricted the right to criticize the President.

Harassment was done to the independent journalist who talked against the government.

Hence, in a democratic government:

Major decisions were taken by the rulers elected by the people. 

Fair choice of people in changing rulers.

Equal opportunity to all the citizens in choosing their representative.

Government’s power is limited by the basic rules of the constitution.

Arguments Against Democracy

Argument of instability may rise because the government is changed frequently:

Political competition and power-play can take the dominance over morality.

Delay in decision making because of multiple consultations.

Lack of knowledge in the public interest can result in wrong decision making.

Democracy is based on electoral competition, it brings corruption.

People electing their representative may be unaware of their wellbeing.

Arguments in Favor of Democracy

A democratic government is always a better government since it is an accountable form of government.

Democracy improves decision making quality.

Democracy gives a method to deal with differences and conflicts.

Democracy enhances citizens' dignity.

Democracy is better compared to other forms of government since it allows us to correct our mistakes.

Broader Meaning of Democracy

Under representative democracy, everyone does not rule. The elected representative takes a decision on behalf of their people:

Modern democracies are characterized by huge populations; which makes it impossible for them to make the right decision.

If they could make the right decision, citizens would not have a greater amount of time, the skill to play a role in all the decisions.

Understanding democracy can help people to identify the weakness of existing democracy and can differentiate between minimal and good democracy.

Democracy in India

India is seen as the largest democracy around the world.

Since independence, citizens have been given the right to vote and have equal rights in voting without considering their caste, religion, gender or color.

Democratic principles by which the Indian government functions are: sovereign, socialist, secular, democratic and republic.

Elections are held after every 5 years.

Government officials work under the Election Commission during election days.

Why Democracy? What are the Merits of Democracy?

The merits of democracy are:

In a democracy, the dignity of citizens is maintained.

It improves the quality of decision making.

Provides a path for resolving conflicts.

The form of government is more accountable.

The government abides by the constitution as it is answerable to the citizens.

What are the Demerits of Democracy?

The demerits of democracy are:

A democratic government might not be stable as the leaders keep on changing.

Morality may not always prevail in the government.

There might be corruption in relation to electoral competition.

Ordinary people would not choose the best leader. They might not have a proper idea about governance.

Did You Know?

There are three songs that garner huge respect internationally for India. These songs uphold the plurality and oneness of Indian democracy:

National Anthem: Jana Gana Mana Adhinayaka Jaya Hey.

National Song: Vande Mataram.

Saare Jahan Se Achchha Hindustan Humara.

To learn more about democracy and its features, go through the What is Democracy Why Democracy Class 9 Notes that is available in a freely downloadable PDF format on Vedantu’s website.

This was a complete discussion on the NCERT Class 9 Political Science Chapter 1 Revision Notes (Free PDF Download). Get your queries resolved by experts at  Vedantu. We follow the updated NCERT criteria for curating the content for CBSE Class 9 Political Science Chapter 1 Revision Notes.

Important Topics Covered in Class 9 Civics Chapter 1 Notes PDF - What Is Democracy? Why Democracy?

The following are the most important topics that are covered in detail in CBSE Class 9 Political Science Chapter 1 What is Democracy Why Democracy Class 9 Notes.

Definition of democracy

Features of democracy

Major decisions by elected leaders

Free and fair electoral competition

One person, one vote, one value one value

Rule of law and respect for rights

Cons of democracy

Arguments in favour of democracy

Broader meanings of democracy

Important Questions: NCERT Class 9 Political Science Chapter 1 - What is Democracy Why Democracy Class 9 Notes

Since we have covered all the important aspects of What is Democracy? Why Democracy? Let us look into some of the important questions in Class 9 Civics Chapter 1 Notes PDF.

Define Democracy.

Democracy is a form of governance in which the people directly or indirectly decide on laws, policies, leadership, and key initiatives for a state or other polity.

Define Representative Democracy.

In a representative democracy, a majority of elected representatives have the authority to make choices on behalf of all the people, rather than all the people ruling or making decisions.

Which kind of Democracy is More Prevalent in the Modern World?

The most prevalent type of democracy in today's world is a representative democracy.

When can we declare elections to be fair?

To be deemed fair, elections must provide voters with a genuine selection of political options.

Define referendum.

A referendum is a general vote in which all voters are asked to accept or reject a proposition.

Frequently Asked Questions:

1. Why is a democratic form of government most popular?

Ans: Some features of democracy make it most popular form of government:

In democracy, the government is accountable for the public interests. Decision making is not completely dependent on the ruler.

This form of government takes all decisions pertaining to the best of their people.

A passive resolution to every predicament is provided in democracy.

Democracy gives the best method for dealing with conflicts in ideology.

Countries like India have a vast diversity of religion, language, castes and creeds, one solution leads to unity.

Political equality is maintained in democracy by giving equal priority to the poor, educated and uneducated.

2. What is direct democracy and why can it not be implemented in modern times?

Ans: Direct democracy is a form of democracy where citizens share an equal role in the decision making process.

Modern democracies consists of a large amount of people, which is not physically possible for them to sit together and make a decision.

All citizens do not have time or skill to take part in entire decision making.

3. Why is the most common form of democratic government is representative democracy?

Ans: Representative democracy is the form of democracy in which the majority of people rule through their elected representative.

This kind of democracy is realistic and huge democracies as all people do not have desired qualifications to rule.

So, direct rule is not possible.

Hence, the majority through their elected representative is allowed to take decisions on behalf of all the people.

So, representative democracy is required where elected people can take collective decisions.

4. What are the basic differences between good and minimal democracy?

Ans: The differences between good and minimal democracy are:

5. What are the common features of a non-democratic government?

Ans: Ideologies of a non-democratic government are:

In non-democratic countries, criticizing the government may lead to oppressive action such as harassment, imprisonment etc.

No elections are held as it is ruled by the king or military.

There is no place for the opposition party.

Unions which abide by the government policies are welcome.

Final words of the dictator or the military rulers are taken into consideration.

Common people cannot think of high positions in government.

6. Give a classic example of a better response of a democratic government over a non-democratic one.

Ans: In China 1958-1961, word recorded famine. The casualties were around three crores of China’s population.

India was economically weaker compared to China, but it was not hit by famine as China.

It was believed it was the government policies of the country that created such a scenario.

Indian democratic responded well to food scarcity. 

Existence of multi-party elections, an opposition party and a press free to criticize the government might have saved China from huge famine casualties.

Advantages of CBSE Class 9 Political Science Chapter 1 What is Democracy Why Democracy Class 9 Notes (Free PDF Download)

The following are some of the most important advantages of referring to the Class 9 Political Science Chapter 1 What is Democracy Why Democracy Class 9 Notes provided by Vedantu.

It covers all the important topics of the chapter.

The concepts are described in precise and easy-to-understand language.

The revision notes are according to the latest CBSE syllabus guidelines.

Chapter 1 Civics Class 9 Notes are the best way to prepare for the exams in an effective manner and shorter time span.

It saves time while allowing candidates to learn all the concepts and thereby reduces revision time.

It helps in developing a better understanding of the topics at just a  single glance.

Check these Exam Preparation Tips With Civics Class 9 Chapter 1 Notes

Let us look at some of the tips that will help students to perform well in the upcoming examinations.

Cover the complete syllabus.

Make revision notes to get the last-minute revision.

Solve previous year's question papers and sample papers.

Always analyse the mistakes and work on them.

Focus on the NCERT exercises and examples as the questions are majorly posed from the NCERT book.

Prepare flowcharts and diagrams to explain the complicated concepts. This would help students to memorise better and also help them to retain information for a longer time.

The Civics Class 9 Chapter 1 Notes provided here are meant to assist students in understanding the key features of constitutional democracy. After reading this Class 9th Civics Chapter 1 Notes, students will be able to distinguish between a democratic form of government and a non-democratic administration. Democracy is the most popular form of governance in use today, and it is spreading to more countries. But, how come? What makes it preferable to other forms of government? Our CBSE Notes Class 9 Political Science Chapter 1 notes address all of these concerns.

You must prepare for your exams by downloading the Revision Notes PDF from Vedantu.

We wish you all the very best for your upcoming examinations!

FAQs on CBSE What is Democracy? Why Democracy? Class 9 Civics Chapter 1 Notes PDF

1. What are the Features of a Democracy?

The features of democracy are as follows:

The rulers of the nation are elected representatives.

There are proper elections held for choosing of rulers.

A rule of law is followed by everybody.

The citizens have a lot of liberty.

An independent judiciary exists.

A political opposition exists.

A democratic government is more accountable for its action than a non-democratic government. Moreover, in case the government is not functioning properly then citizens can vote for other leaders.

2. How should one study Class 9 Democratic Politics?

Class 9 political science is a pretty interesting subject. Students often end up mugging up this subject instead of trying to understand it. Political science is a very relevant subject that affects us in our daily lives. So, approach it in a way to understand its concepts and their applicability in our lives. Read the textbook well and then refer to extra study notes and NCERT 

Solutions to broaden your understanding of the chapter.  

3. What are the study resources offered by Vedantu for Class 9 Political Science Chapter 1?

Vedantu makes sure that it offers an array of study tools to benefit the students of all classes. Vedantu offers the following resources for Class 9 Political Science Chapter 1:

NCERT Solutions 

Revision notes

Important questions

Sample papers

Previous years' question papers 

Masterclasses

 Demo classes

Conceptual videos

Interactive Classes

Students can access these beneficial tools from Vedantu 's website and mobile app at free of cost. 

4. What is the significance of Chapter 1 “What is Democracy? Why Democracy?”

Class 9 Political Science Chapter 1 "What is Democracy? Why Democracy?" is indeed an important chapter. It teaches the students about the fundamental principles of democracy. Additionally, the chapter tries to explain these principles via examples of different countries which do not fulfil the requirements of being true democracies. It introduces the students to the significance of democracy. The chapter also teaches the students the broader meaning of democracy. 

5. What is democracy and why do we need democracy?

Democracy is a form of government in which the rulers are elected by the people through the process of elections. It is a form of government that holds its leaders accountable to the people.  We need democracy because other forms of government are not held accountable to the people. Democracy is indeed a better form of government as it ensures maintaining law and order and equal rights in a country.

6. What is the significance of democracy?

Several significant features of democracy make it better than other forms of government. These include the fact that democracy makes the government accountable to its citizens. It allows for a better decision-making process and paves the way to resolve conflicts. In a democracy, citizens are treated as dignified, equal citizens who have the power to choose their leaders.  This improves the quality of the decision-making process in a democracy.  

7. What are the challenges to democracy discussed in Class 9 Political Science Chapter 1 Notes?

The chapter discusses challenges such as corruption, inequality, discrimination, political apathy, and the rise of authoritarianism, highlighting the importance of addressing these issues to strengthen democratic institutions and practices.

8. How does Chapter 1 of Class 9 Civics explore the concept of democracy?

The chapter explores democracy through historical examples, contemporary case studies, and theoretical discussions. It examines different forms of democracy and highlights the principles and institutions that sustain democratic governance.

9. What are some real-life examples discussed in Class 9 Political Science Chapter 1 Notes to illustrate the functioning of democracy?

Examples include the functioning of democracies in India and other countries, the role of citizens in elections and decision-making processes, and instances of democratic struggles and movements for rights and freedoms.

10. What is the main focus of Class 9 Ch 1 Civics Notes: What is Democracy? Why Democracy?

The main focus of this chapter is to understand the meaning and significance of democracy. It explores the concept of democracy, its principles, and why it is considered a preferred form of government.

11. What are the key concepts covered in Chapter 1 of Class 9 Civics?

The key concepts covered include the meaning of democracy, its features, the importance of democracy in ensuring equality and justice, the role of citizens in a democratic society, and the significance of democratic values.

12. What are the objectives of studying Class 9 Ch 1 Civics Notes?

The objectives include in Class 9 Ch 1 Civics Notes are understanding the principles and functioning of democracy, recognizing the importance of citizen participation in a democracy, analyzing the challenges faced by democratic societies, and appreciating the values inherent in democratic governance.

13.  How can I use my Class 9th Civics Chapter 1 Notes effectively for exam preparation?

Review your Class 9th Civics Chapter 1 Notes regularly to reinforce your understanding of the chapter. Use them as a reference while practicing questions, solving sample papers, or revising for exams. You can also create flashcards or mind maps based on your notes to aid in memory retention and concept clarification.

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Question 2 - Case Based Questions - Chapter 1 Class 9 Political Science - What Is Democracy? Why Democracy - Political Science

Last updated at April 16, 2024 by Teachoo

Read the source given below and answer the  questions that follow: 

  In Pakistan, General Pervez Musharraf led a  military coup in October 1999. He overthrew a  democratically elected government and declared  himself the ‘Chief Executive’ of the country. Later  he changed his designation to President and in  2002 held a referendum in the country that granted  him a five-year extension. Pakistani media, human  rights organisations and democracy activists said  that the referendum was based on malpractices  and fraud. In August 2002, he issued a ‘Legal  Framework Order’ that amended the Constitution  of Pakistan. According to this Order, the President  can dismiss the national and provincial assemblies.  The work of the civilian cabinet is supervised by  a National Security Council which is dominated  by military officers. After passing this law,  elections were held to the national and provincial  assemblies. So, Pakistan has had elections, elected  representatives have some powers. But the final  power rested with military officers and General  Musharraf himself.  

Question (i)

Who led a military coup in october 1999  and overthrew a democratically elected  government  .

(a) Nawaz Shariff  

(b) General Pervez Musharraf  

(c) Imran Khan  

(d) Benazir Bhutto 

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Pak Study 9th Class Chapter 1 Pdf

Are you looking for Pak Study 9th Class Chapter 1 Pdf Notes? You are at the right place. You can download the complete exercises, short questions and MCQs of the unit 1.

Chapter 1 of the 9th class notes covers the ideological basis of Pakistan, which is the vision of a separate homeland for the Muslims of India. The chapter explains the historical, religious, cultural, and political factors that led to the demand for Pakistan. It also discusses the role of various Muslim leaders and movements in shaping the ideology of Pakistan.

The chapter provides a comprehensive overview of the concept and significance of Pakistan as an Islamic state.

Pakistan Studies is one of the optional subject offered for the Civil Services Main Examination. It was introduced in the year 1991 and replaced the Indian History optional. Pakistan Affairs can be considered as a combination of Political Science and International Relations, with a focus on Pakistan.

It is a fact that competition in Pakistan Studies have decreased considerably over the years. And it is not because of the difficulty in this subject, but because of the difficulty in availing good books. Most of the candidates either rely on notes or select other optional subjects.

But there are still some things worth considering before giving up on Pakistan Studies:

The syllabus is short and easy to grasp, as compared to other optional subjects, like Geography .

There are not many applicants in this subject. This means there will be less competition, and therefore more chances of scoring higher marks!

Pak Study 9th Class Chapter 1

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Extra Questions for Class 9 Civics Chapter 1 What is Democracy? Why Democracy?

Class 9 Social Science Civics Chapter 1 What is Democracy Why Democracy extra questions and answers available here in PDF format. Solving class 9 extra questions help students to revise the Chapter most competently. We prepared these questions with PDF as per the latest NCERT book and CBSE syllabus. Practising these questions before the exam will ensure excellent marks in the exam.

Class 9 Civics Chapter 1 Extra Questions and Answers

Very short answer questions.

1: Which party of Zimbabwe helped its country to gain independence? Answer:  The ZANU-PF party of Zimbabwe helped its country to gain independence.

2: Which Pakistani general led a military coup in October 1999? Answer:  The Pakistani general who led a military coup in October 1999 was General Pervez Musharraf. 

3: Since 1930, which country holds elections after every six years and which has never been under a military or dictator’s rule? Answer:  The country is Mexico. 

4: Zimbabwe attained independence from white minority rule in which year? Answer:  Zimbabwe attained independence from white minority rule in 1980. 

5: During which period did China record its worst famines in world history? Answer:  China’s famine of 1958-1961 was the worst recorded famine in world history. Nearly three crore people died in this famine. 

6: Which one country out of France, USA, Myanmar and India is not a true democratic country? Answer:  Myanmar is not a true democratic country because it is ruled by military rulers. 

7: In Iraq, the real powers are held by which outside country? Answer:  The real powers in Iraq are held by the USA.

Question than that of migrants from other countries? Answer:  In Fiji, the electoral system is such that the vote of an indigenous Fijian has more value than that of an Indian-Fijian (Fijian who is a  descendent of migrants from India.

9: What are the major challenges to the working of democracy in India? Answer:  Casteism and communalism are the major challenges to the working of democracy in India. 

10: Is it true of democracy that it allows a way of correcting its mistakes and offers more dignity to all citizens? Answer:  It is true, because elections are held regularly in a democracy every few years, thus allowing a way of correcting our mistakes. It offers more dignity to all citizens by treating all of them equally. 

11: Name the famous political party of Mexico. Answer:  The famous political party of Mexico is Institutional Revolutionary Party (PRI). 

12: What is the most common form of democracy in today’s world? Answer:  The most common form of democracy in today’s world is representative democracy.

13 : Where did democracy make its first formal appearance in the 5th and 6th century BC? Answer:  Democracy made its first formal appearance in the Greek city states during the 5th and 6th century BC. 

14 : What are the three types of government practiced in Belgium? Answer:  The three types of government practiced in Belgium are Central Government, State Government and Community Government. 

15 : Which one country out of Bangladesh, USA, Saudi Arabia and India has the lowest participation of women in public life? Answer:  Saudi Arabia has the lowest participation of women in public life. 

16 : Name the capital of Republic of Fiji. Answer:  Suva is the capital of Republic of Fiji. 

17 : Which form of Government is present in Fiji? Answer:  Fiji is Parliamentary republic run by military appointed government. 

18 : When did Estonia restore its independence from the Soviet Union? Answer:  Estonia, a state in the Baltic region at Northern Europe got independence from the Soviet Union an 20th August, 1991. 

19 : Name the capital and official language of Estonia. Answer:  The capital of Estonia is Tallinn and the official language is Estonian. Other recognised regional languages are Voro, Setu. 

20 : Explain the type of government present in Mexico. Answer:  The United Mexican states are a federation whose government is representative, democratic and republican based on a presidential system according to the 1917 Constitution. 

21 : On which respect Saudi Arabia in the only country in the world? Answer:  Saudi Arabia is the only country in the world which ban womens from driving. 

22 : What was the designation taken by pervez Musharraf for himself when he overthrew the democratic government of Pakistan in 1999? Answer:  Pervez Musharraf declared himself the Chief Executive of Pakistan when he overthrew the democratic government of Pakistan in 1999. 

23 : ‘Banning Trade Unions’-is it a characteristic of democracy or not? Answer:  ‘Banning Trade Unions’ is not a characteristic of democracy. Ans. In democracy, people can choose their own leaders. 

24 : Suggest one of the important features of democracy Answer:  According to this order, the President can dismiss the national or provincial assemblies and the final power rests with military officers and General Musharraf himself. 

25. Which members are allowed to contest for the elections in China? Answer:  Only those who are members of the Chinese Communist Party or eight smaller parties allied to it were allowed to contest elections held in 2002 – 03. The government is always formed by the Communist Party. 

26. What was PRI? Answer:  It was a political party of Mexico called as Institutional Revolutionary Party. 

27. How can you say that people did not have any choice in democratic Mexico? Answer:  People seemed to have no choice. There was no way the ruling party PRI could be defeated, even if people were against it. There were no fair elections. 

28. What does the true democracy say? Answer:  A democracy must be based on a free and fair elections where those currently in power have a fair chance of losing.

29. In which country women do not have the right to vote? Answer:  Saudi Arabia. 

30.What is the electoral system in Fiji? Answer:  In Fiji, the vote of an indigenous Fiji has more value than that of an Indian Fijian.

31. When did Zimbabwe attain independence? Answer:  Zimbabwe attained independence from white minority rule in 1980. 

32. Which party is ruling over Zimbabwe since independence? Answer:  ZANU-PF is the party that is ruling over Zimbabwe since independence. 

33. Who is the President of Zimbabwe? Answer:  President Robert Mugabe. 

33. What do you derive from democratic government like Zimbabwe’s? Answer:  Popular governments can be undemocratic and popular leaders can be autocratic. 

34. Give any one demerit of democracy. Answer:  Leaders keep changing in a democracy. This leads to instability. 

35. Give any one merit of democracy. Answer: A democratic government is a better government because it is more accountable form of government and it enhances the dignity of citizens. 

36. How democracy allows us to correct its own mistakes? Answer:  In democracy there is space for public discussion on government’s or rulers’ mistakes and there is a room for correction. Either the rulers have to change their decisions, or the rulers can be changed. 

37. How does democracy enhance the dignity of citizens? Answer:  Democracy is based on the principle of political equality, on recognising that the poorest and the least educated has the same status as the rich and the educated. 

38. Why modem democracies are representatives democracies? Answer:  Modern democracies involve such a large number of people that it is physically impossible for them to sit together and take a collective decision. 

39. What is the basic sense behind a method of taking decision in democracy? Answer:  A democratic decision involves consultation with and consent of all those who are affected by that decision.   

40. Define the term ‘Democracy’. Answer:  Democracy is a form of government in which the rule over the country is of the people, for the people and elected by the people. E.g: India. 

41. What does a candidate need before contesting elections in China? Answer:  A candidate needs the approval of the Chinese Communist Party before contesting elections in China. 

42. Who said this : ‘Democracy is the rule of the people, for the people and by the people’? Answer:  Abraham Lincoln, the former President of USA said this. 

43. The King of which country has declared that in future he will be guided by the advice given to him by elected representatives? Answer:  King of Bhutan has declared that in future he will be guided by the advice given to him by elected representatives.

Short Answer Type Questions

1. Why were every elections won by PRI in Mexico?

Answer:  PRI managed to win elections in Mexico every six years because they used many unfair means to win elections. Like they spent a large sum of money in the campaign for its candidates and forced people to vote for them. 

2: Government has not made any provision for drinking water in some villages in remote areas. The villagers of a particular remote area decided to pay some money to the government officials to get water to their villages. Was this a democratic method?

Answer:  No, this was not a democratic method. They could have organised public meetings against government’s policies, filed a case in the courts claiming that water is part of the right to life, or even boycotted the next elections to give a message to all parties, which are all democratic methods. 

3 : Do the women of Saudi Arabia have the right to vote?

Answer:   On 25th September, 2011, Saudi Arabia’s king Abdullah has announced that women will have the right to stand and vote in future local elections and join the advisory Shora, a council as full members. 

4: What kind of government does Zimbabwe have?

Answer:   Zimbabwe is a republic with a presidential system of government. But now the country is effectively authoritarian dictatorship under President Robert Mugabe who has re-elected in 2013 at the age of 89 for another five years.

5. How President Mugabe changed the constitution of Zimbabwe?

Answer:  President Mugabe has changed the constitution several times to increase the powers of the President and make him less accountable. Public protests and demonstrations against the government are declared illegal. There is a law that limits the right to criticise the President. 

6: With what motive did General Pervez Musharraf issue a ‘Legal Framework order’ in August 2002?

Answer:  In august 2002 he issued a legal framework order that amended the constitution of Pakistan. In this order the President can dismiss the national and provincial assemblies. After passing this law elections were held to the national and state assemblies. So the election were held regularly and power rest with elected representatives. But still the final power rests with military officers and muhraff himself.

7. From which word or words, has the word ‘Democracy’ been derived?

Answer:  The word ‘Democracy’ is derived from the Greek words – ‘Demos’ and ‘cratia’. ‘Demos’ means ‘people’ and ‘cratia’ means ‘power’. Thus, Democracy means a form of government in which the power to rule lies in the hands of the people.

8. What is direct democracy?

Answer:   It is a form of government in which people directly participate in the affairs of the state. This system is possible only in those states where the population is small and all the citizens can directly participate in the affairs of the state. All the adult citizens have the right to participate in the meetings of the Assembly where all the laws are passed and decisions are taken. Today this system exists only in a few cantons of Switzerland. 

9. What do you understand by ‘indirect democracy’?

Answer:  Indirect democracy has been established in almost all the modern states, because modern states are much larger in size and population than before. Here people do not directly taken part in the affairs of the state, but they elect their representatives for a fixed period. If the representatives do not work according to the wishes of the people and for their welfare, they are changed at the time of the next election. 

10. How does democracy enhance the dignity of the citizens?

Answer:  Democracy is based on the principle of political equality. It means that the poorest and the least educated have the same status as the rich and the educated. People are not subjects of a ruler, they are the rulers themselves. Even when they make mistakes, they are responsible for their own mistakes.

11. This cartoon was published in Canada just before its Parliamentary elections of 2005. Everyone, including the cartoonist, expected the Liberal Party to win once again. When the result came, the Liberal Party lost the elections. In this cartoon an argument against democracy or for democracy?

Answer:   This cartoon is an argument for democracy. Because in democracy, the voters decide in favour of or against the ruling party. Although the cartoonist expended the Liberal Party to win, he criticised the Liberal Party which he could do only in a democracy.

12. This cartoon was titled ‘Building Democracy’ and was first published in a Latin American Publication.  (i) What do money bags signify here?  (ii) Could this cartoon be applied to India?

Answer:  (i) At the time of election, the political parties in the fray spend a lot of money to win the election. Not only political parties, the government also spends a lot of money to conduct free and fair election. The cartoon suggests that we establish democracy with the help of money power. (ii) Yes, this cartoon could be applied to India. 

13. Chinese Government blocked free flow of information on the internet by placing restrictions on popular websites like ‘Google’ and ‘Yahoo’. The image of tanks and an unarmed student reminds the reader of another major event in recent Chinese history. Find out about that event. 

Answer:   The cartoon reminds us of the Massacre in liananmen square in 1989. In April 1989, triggered by the death of Hu Yaobang, a liberal reformer, mass gathering and protests took place in and around Tiananmen Square in Beijing. It was largely a student run demonstration which called for economic reform, freedom of the press and political liberalisation. The Chinese Government brutally suppressed the movement for which it was internationally 

14. I want to be in Lyngdoh Madam’s class! That sounds like a democratic classroom, doesn’t it?

Answer:   Yes, Lyngdoh Madam’s classroom sounds like a democratic classroom. Here everybody can speak his own mind. The students are giving their own arguments passionately. The feel very bad if someone that the environment in the classroom is democratic.

15. Why is democracy considered the best form of government?

Answer:  Democracy cannot give us everything but is clearly better than any other alternative. It offers better chances of a good decision, it is likely to respect people’s wishes and allows different kinds of people to live together. Even when it fails to do some of these things. It allows a way of correcting its mistakes and offers more dignity to all citizens. That is why democracy is considered the best form of government.

16. How does democracy allow us to correct its own mistakes?

Answer:   There is no guarantee that mistakes cannot be made in democracy. No form of government can guarantee that. The advantage in a democracy is that such mistakes cannot be hidden for long. There is a space for public discussion on these mistakes. And there is room for correction. Either the rulers have to change their decisions or the rulers can be changed. This cannot happen in a non-democratic government.

17. How does democracy improve the quality of decision making?  

Answer:  A democratic decision involves consultation with and consent of all those who are affected by that decision. Those who are not powerful have the same say in taking the decisions as those who are powerful. This can apply to a government or a family or any other organisation. The chance of rash or irresponsible decision is also less in a democracy.

18. What would have happened if India was not a democracy? Could we have stayed together as a single nation?

Answer:   No, we would have not stayed together as a single nation if India was not a democracy. India has multi-religious, multi-cultural and multi-linguistic population. If there was no democracy then all the people could not have followed their religion and customs with freedom and there would have been conflicts between different religious and linguistic groups where the minorities would have lived in fear and insecurity. But democracy provides the peaceful solutions to every problem. It provides the best method of dealing with differences and conflicts. 

19. What according to you is the broader meaning of democracy?

Answer:  Democracy is a form of government in which representatives of an area in a country sit together to take decisions. Elections are held to choose the representatives and native people or citizens are allowed to participate in the elections. Democracy is also a principle that can be applied to any sphere of life. 

20. How does democracy enhance the dignity of the citizens

Answer:  Democracy is based on the principle of political equality, on recognising that the poorest and the least educated has the same status as the rich and the educated. People are not subjects of a ruler, they are the rulers themselves. Even when they make mistakes, they are responsible for their conduct.

21. How democracy can enhance the dignity of the citizens?

Answer:   (i) Democracy is based on the principle of political equality, on recognising that the poorest and the illiterate has the same status as rich and the educated. (ii) People are not subjects of a ruler, they are the rulers themselves. (iii) Even when they make mistakes, they are responsible for their conduct.   

22: Write three arguments in favour of democracy.

Answer:  Arguments for democracy are (i) A democratic government is a more accountable form of government. A democracy requires that the ruters have to attend to the needs of the people. (ii) Democracy is based on negotiation and deliberation, which improves the quality of decision-making. (iii) It allows us to correct our own mistakes. In democracy there is always a scope that the rulers can change their wrong decisions or the rulers themselves can be changed.

23: Is China a democratic country or not? Give two arguments in favour of your answer.

Answer:   China is not a democratic country in the true spirit. (i) For contesting the election to the Chinese Parliament, the candidates need the approval of the Chinese Communist Parry. Only the members of Communist Party and its eight allies are allowed to contest the election. (ii) There is one party rule, i.e., Communist Party in China, which is not the indication of a true democracy. Therefore, China cannot be said to be a true democracy.

24: Examine any three demerits of democracy.

Answer:   Some demerits of democracy are (i) Leaders keep changing in a democracy. It leads to instability. (ii) Democracy is all about political competition and power play. Here political parties try to win elections spreading caste feelings, communalism, practising immoral methods etc. (iii) So many people have to be consulted in a democracy that it leads to delays. Involving people in the decision-making does lead to delay which is not desirable for the nation. 

25: Describe four features of democracy as a form of government.

Answer:  The features of democracy are (i) Democracy is a form of government in which the rulers are elected by the people. (ii) A democracy must be based on a free and fair election, where those currently in power have a fair chance of losing. (iii) In a democracy, each adult citizen must have one vote and each vote must have one value. (iv) In a democracy, government rules within limits set by constitutional law and citizens rights. 

26: Explain any three difficulties faced by the people in a non-democratic country.

Answer:  Three difficulties faced by the people in a non-democratic country are (i) In a non-democratic country, all the people are at the mercy of the dictator or the military rulers. They may or may not respond to the people’s need. (ii) In non-democratic countries, the people are not allowed to criticise the government. By doing this people may face imprisonment, harassment, etc. (iii) In a non-democratic country, no opposition is tolerated, so the question of opposition party or trade unions does not arise. 

27: How does democracy allow us to correct our own mistakes?

Answer:   There is no guarantee that mistakes cannot be made in a democracy. Actually, no form of government can guarantee it. The advantage of democracy is that mistakes cannot be hidden for a long time. There is always a scope for a public discussion of mistakes in democracy. In democracy, all citizens can take part and there is room for correction. Either the rulers have to change their decisions or the rulers themselves can be changed in democracy. 

Long Answer Type Questions

1: Write any three instances of denial or equal right to vote in the world politics. Or Why are China, Estonia and Saudi Arabia not truely democratic countries? State one reason to each one of them. Or Why are China and Saudi Arabia non-democratic countries though they declared themselves as democracies? State one reason to each of the countries.

Answer:  One major demand of democracy is ‘Universal adult franchise’ i.e., right to vote for every adult citizen. But in the world politics there are many instances of denial of equal right to vote. In Saudi Arabia women did not have the right to vote until 2011. On 25th September, 2011, king Abdullah has declared that women will have the right to stand and vote in future. Estonia made its citizenship rule in such a manner, that people belonging to Russian minority find it difficult to get the right to vote.

In China, before contesting the election, the needs the approval of the Chinese Communist Party. Although the countries declare themselves as democracies, but the fundamental principle of ‘political equality’ is denied in all the Cases. Thus, these are not truly democratic countries. 

2: State the freedoms which are usually taken away when democracy is overthrown by a military regime.

Answer:  The freedoms usually taken away by a military regime are (i) There will be no freedom of expression and speech. (ii) In a non- democratic government, the rulers do not have to act according to the wishes of the people. The needs of the people can be ignored by the military ruler. (iii) In democracy, no one is a permanent loser or winner. But in military regime same ruler or ruling party can rule the country for a very long time. (iv) In non-democratic country, there is no freedom to form political associations and organize protests and political action. In reality, political freedom of the citizen is completely denied in military regime. 

3: ‘Democracy is all about political competition and powerplay. There is no scope for morality’. Justify the statement by giving arguments against democracy.

Answer:  Democracy as a form of government only ensures that people can take their own decision. It does not guarantee that their decisions will be good always. In democracy leaders keep changing which leads to instability. Democracy is based on consultation and discussion, but so many people have to be consulted in a democracy that if leads to delay.

Elected leaders do not know the best interest of the people. It leads to bad decisions. As democracy is all about political competitions it leads to corruption. Political parties utilise many corrupt tricks to win the election. Ordinary people do not know what is good for them. People can make mistakes so they should not decide anything. 

4: ‘Democracy is better than any other form of government, because it allows to correct its own mistakes. Justify the statement with the help of three examples. Or Democracy is better than other forms of government because it allows us to correct own mistakes. Discuss.

Answer:  Democracy always offers scope for correction which is impossible in any other form of government. No form of government is free from mistakes. Democracy also involves many mistakes. But the good thing is that it allows to correct its own mistakes.   The advantage of democracy is that, if there is any mistake, it cannot be hidden for long. Sooner or later the public comes to know about them.

There is always space for public discussion on these mistakes. And there is a room for correction. Correction of mistakes results in either the rulers have to change their decision or the rulers themselves can be changed through election. This cannot happen in a non-democratic government.

5. How does democracy improve the quality of decision-making?

Answer:  Democracy is based on consultation and discussion. A democratic decision always involves many persons, discussions and meetings. Those who are not powerful have the same say in taking the decisions as those who are powerful. When many people put their heads together, they are able to point out possible mistakes or drawbacks in any decision. It takes time. But important decisions should be taken after proper discussion. This process may be time-consuming, but it reduces the chances of rash or irresponsible decisions. Thus the lengthy process of taking decisions on any important issue in democracy improves the quality of the decision. 

6. Explain the difficulties faced by the people in a non-democratic country? 

Answer:  The common difficulties faced by the people in a non-democratic country are (i) People cannot choose or change their ruler. (ii) People cannot question the authority of the ruler or dictator. (iii) People do not enjoy any rights. Supporters of democracy are tortured or killed. For example, in Chile more than 3000 people were killed by military. (iv) In a non-democratic country, public protests and demonstration against the government are declared illegal. Sometimes political activists are imprisoned for   indefinite time. For example, Aung San Suu Kyi in Myanmar spent a long time in under house arrest. (v) In a non-democratic country, people do not have political equality. Universal adult Franchise is denied sometimes. (vi) In a non-democratic country people may have elected their representatives, but in reality they are not really the rulers. The power of taking final decision rests with army officials. For example, in Pakistan, the real power is enjoyed by the army. 

7. “Democracy is the most popular form of government emerging in modern times. Still its shortcomings cannot be ruled out.” Justify the statement by assessing any five shortcomings of democracy.

Answer:  Shortcomings of democracy are (i) In the democratic form of government, leaders keep on  changing, which leads to instability. (ii) There is political competition and power play everywhere. This situation hardly follows any rules of morality. (iii) Elected leaders are unable to contact a large number of people and can hardly guess about the real problems of the people, which results in wrong decisions, delay of work, etc. (iv) A large number of people are illiterate. They do not know what is good for them. So they cannot decide anything properly. (v) Democracy leads to corruption for it is based on electoral competition. To win the election, the political parties adopt their own policies and try to win election by hook or by crook. 

8. How did. Musharraf establish his rule in Pakistan?

Answer:  General Pervez Musharraf led a military coup in Pakistan in October 1999. He overthrew a democratically elected government and declared himself the Chief Executive of the country. Later the changed his designation to President. In 2002, he held a referendum in the country that granted him a five year extension. In August, 2002, he issued a ‘Legal Framework Order’ that amended the Constitution of Pakistan. According to this order, the President can dismiss the national or provincial assemblies. A National Security Council dominated by military officers supervised the work of the civilian cabinet. After passing the ‘Legal Framework Order’ Law, elections were held to the national and state assemblies.  

9. How did Robert Mugabe establish his dictatorial rule in Zimbabwe after independence?

Answer:   Zimbabwe attained independence from white minority rule in 1980. After independence, the country has been ruled by ZANU-PF, the party that led the freedom struggle. Its leader Mugabe has been ruling since independence. Mugabe is popular, but also uses unfair practices in elections. Over the years, his government has changed the constitution several times to increase the power of the President and make him less accountable. Opposition party workers are harassed, public protests against the government are declared illegal and both electronic and print media are controlled by the government. Even the government ignores the court judgements that go against it. He has re-elected in 2013 at the age of 89 for another five years. His supporters characterise him as a true Pan-Africanist who stands strong against forces of imperialism in Africa.  

10. Write a response to the following arguments against democracy.  (a) Army is the most disciplined and corruption-free organisation in the country. Therefore Army should rule the country.  (b) Rule of the majority means the rule of ignorant people. What we need is the rule of the wise, even if they are in small numbers.  (c) If we want religious leaders to guide us in spiritual matters, why not invite them to guide us in politics as well. The country should be ruled by religious leaders.

Answer:  (a) The Army is for the defence of the country. Even if it is the most disciplined and corruption-free organisation it should not be allowed to rule the country as its primary duty is defence and not governance. (b) Rule of majority is democratic as it represents the views of all sections of people. Illiterate and poor people cannot be called ignorant. At least they can realize which representative is good for them. Democracy means equal opportunity to all without any discrimination (c) This statement is wrong. We should not mix religion and politics, especially in a multi-racial, multi-religious and multi-lingual country like India, Besides, many religious leaders do not have any experience of administration.

11. Are the following statements in keeping with democracy as a value? Why?  (a) Father to Daughter I don’t want to hear your opinion about your marriage. In our family, children marry what the parents tell them to.  (b) Teacher to Student Don’t disturb my concentration by asking me Questions in the classroom.  (c) Employee to the Officer Our working hours must be reduced according to the law.

Answer:   (a) The first statement is undemocratic because a girl is not allowed to give her opinion relating to her own marriage. Just as the people have the right to choose their representatives, the girl should also be allowed to have a say in the selection or choice other husband. (b) The second statement is undemocratic because the student is not being allowed to speak and ask questions. It is the duty of the teacher to teach and satisfy the queries of the students. (c) The third statement is democratic because it calls for the reduction of working hours according to the law. Employees should enjoy the right to work for fixed hours as fixed by international law. 

12. Why is democracy considered the best form of government?

Answer:   Democracy has been accepted as the best form of government in the modern world. Under this, government works for the welfare of the people. Democracy performs better regarding the removal of poverty and backwardness in a country. It offers better conditions of living. It implements policies to ensure equal opportunities for all the citizens in education and employment. Democracy is likely to respect people’s own wishes and allows different kinds of people to live together. Even if it fails to deliver on some of its promises, always there is a scope to correct its mistakes. Above all, it offers more dignity to all citizens. That is why democracy is considered the best form of government.

13. Is Mexico a democratic country or not? Give arguments in favour of your answer.

Answer:  Mexico became independent in 1930. It holds elections after every six years. But until 2000, every election was won by a party called PRI (Institutional Revolutionary Party). PRI used many dirty tricks to win the elections. It spent a large sum of money for its candidates. Opposition parties did contest elections, but never managed to win. Media largely ignored the activities of the opposition political parties. But from 2000 the scenario has changed. In the 2000 election, Vicente Fox of National Action Party (PAN) in alliance with Ecologist Green Party of Mexico (PVEM) became the first opposition candidate to win the election. Vicente Fox became the President of Mexico. After him Felipe Calderone of National Action Party (PAN) again became the President. It suggests that Mexico has marched towards democracy. 

15. Explain the representative democracy. Why is the representative democracy the most common form of government in modern times? Explain any four reasons. Or What is the representative democracy? Discuss its significance in the contemporary world.

Answer:  The most common form of democracy in present time is that of a representative democracy. It is a type of democracy founded on the principle of elected representatives representing a group of people as opposed to direct democracy. (i) India and most of the countries follow the representative democracy. In a democracy, all the people do not rule. Direct rule by people is not possible. (ii) In a democracy, a majority is allowed to take decisions on behalf of all the people. Even the majority does not rule directly. It rules through its elected representatives. (iii) Representative democracy becomes necessary in the contemporary world. Because modern democracies involve such a large number of people that it is physically impossible for them to sit together and take a collective decision. (iv) Even if they could, the citizens do not have the time, desire or skill to take part in all the decisions. 

16. Elections in China do not represent people’s verdict. Explain. Or Why are elections in China not free and fair? Explain any three reasons. Or Why can’t the democratic set up in China be called a true democracy? Explain.

Answer:  

(i) Democracy is a major concept introduced to China in the late 19th century. (ii) In China, elections are regularly hold after every five years for electing the country’s Parliament, called National People’s Congress. (iii) It has nearly 3000 members elected from all over China. Some members are elected by the army. (iv) This National People’s Congress has the power to appoint the president of the country. (v) Before contesting elections, a candidate needs the approval of the Chinese Communist party. (vi) Only those who are members of the Chinese Communist Party or eight smaller parties allied to if are allowed to contest elections in China. (vii) The government is always formed by the communist party.   (viii) Thus, we cannot say that the elections in China are  free and fair. It is always restricted by the communist   party.

17. What steps were taken by PRI to win election in Mexico? Or The Institutional Revolutionary Party (PRI) used many dirty tricks to win elections in Mexico”. Justify the statement with five example. Or Describe any five dirty tricks used by PRI to win elections in Mexico. Or “Till 2000 Mexican people seem to have a choice to elect their leader but practically they had no choice.” Support this statement with three suitable reasons.  

Answer: The Institutional Revolutionary Party (PRI) of Mexico won all the elections from 1930 to 2000. The opposition parties did contest elections, but never managed win. The PRI used many dirty tricks to attend the elections. (i) All the government employees had to attend the party meetings of PRI.\ (ii) Teachers of government schools advised and sometimes forced the parents for casting their votes in favour of PRI. (iii) Media always criticised the opposition parties but ignored their good effort. (iv) Sometimes the Polling booths are shifted from one place to another without prior notice. It tried to hamper the election procedure. (v) Being in power, the PRI spent a large sum of money to manipulate the election and the campaign for the candidate. In Mexico people seemed to really have a choice, but in reality they had no choice, but to cast their vote in favour of the PRI. 

18. I have heard a different version. Democracy is off the people far (from) the people and (where they) buy the people. Why don’t we accept that?

Answer:   In some cases, the democracy is off the people far (from) the people and (where they) buy the people i.e., where the democracy does not belong to the people it is not for them but far away from them, where the democracy is not by the people but the candidates the votes with money which means that true democracy does not exist. But we should not see these examples and be hopeless. These cases are exceptions and not the rule, which will be removed with the passage of time.

19. Let us take Lyngdoh Madam seriously and try to write down the exact definition of some of the simple words that we use all the time : pen, rain and love. e.g., is there a way of defining a pen that distinguishes it clearly from a pencil, a brush, a chalk or crayon.  (i) What have you learnt from this attempt?  (ii) What does it teach no about understanding the meaning of democracy?

Answer:   (i) From this conversation, I have learnt that there is no shortest to our thinking about the matter ourselves. We have to think about its meaning and evolve a definition. Each and every thing has some specific features on the basis of which we can define that thing. (ii) We need a definition only when we come across a difficulty in the use of a word. We need a clear definition of democracy because there are different kinds of governments which are known as Democracy. Abraham Lincoln said that Democracy is a rule of the people, for the people and by the people. We must not accept the definition, jug. because everyone accepts it. We do not know if this is the best way of defining democracy unless we think about it ourselves. After thinking about it we can say that democracy is a form of government in which the rulers are elected by the people. This is a common basic feature of democracy.

20. Syria is a small West Asian country. The ruling Ba’ath Party and some of its small allies are the only parties allowed in that country. (i) Do you think this cartoon could apply to China or Mexico?  (ii) What does the crown of leaves on democracy signify?

Answer:  (i) Yes, this cartoon could be applied to China, because there is one party rule in China. Before contesting elections, a candidate needs the approval of the Chinese communist party. So China cannot be said fo be a true democracy. Mexico has a multiparty system. Nationally there are three large political parties, viz, Institutional Revolutionary   Party (IRP), National Action Party (NAP), and Party of the Democratic Revolution (PDR). But until 2000 every election was won by the PRI. The PRI was known to use many dirty tricks to to win elections. So the cartoon can be applied to Mexico until 2000 election. But in 2006, election the PRI fell to third place behind both the PAN and the PRD. Now Mexico has a coalition government. (ii) Crown of leaves means a circle of leaves that is worn on somebody’s head as a sign of victory. The cartoon signifies that democracy has won in some of the countries of the world, but it is not accepted by all. 

21. This cartoon was drawn in the context of Latin America. (i) Do you think it applies to the Pakistani situation as well? (ii)Think of other countries where this could apply?  (iii) Does this happen sometimes in our country as well?

Answer:   (i) The cartoon suggests the scene of booth capturing with the gun. This can be applicable to the Pakistan. In Pakistan, General Musharraf with the help of army officials   controlled the elected representatives. (ii) This could be applied in Iraq, China, etc. (iii) Booth capturing by the political hooligans happens sometimes in our country also. 

22. All this is so remote for me.  (i) Is democracy all about rulers and governments? (ii) Can we talk about a democratic classroom? (iii) Or a democratic family?

Answer:  (i) Democracy is not only about rulers and governments. Democracy is a principle that can be applied to any sphere of life. A democratic decision involves consultation with and consent of all those who are affected by that decision. In this sense, it can be applied to any organisation other than the government.

(ii) We can have democratic classrooms where the students can ask questions without hesitation. Where the teachers have a democratic temperament. Where the interaction is not a one-way traffic but a healthy two-way interaction.

(iii) Democracy can be seen in families also. We could have democratic families where the decisions are not taken by any one individual and imposed on rest of the family members. All the family members should sit down and arrive at a general consensus. My opinion should matter as much as my father’s. In this way, we can have, democracy in our family also.

23. This cartoon is about the Iraqi election held after Saddam Hussein’s regime was overthrown. He is shown behind the bars.  (i) What is the cartoonist saying here?  (ii) Compare the message of this cartoon with the first cartoon in this chapter.

Answer:  (i) In one of the quotation of the cartoon, the cartoonist tells us about the equality of the right to vote and equal value of each man’s vote. In another quotation, he says that the dicta top, mostly prefers the situation when he is the only man to decide any matter by his only vote. (ii) The first cartoon shown in two chapter suggests that the US army personnel are elevating the process to form a democracy in Iraq. But in this cartoon the message is that the democracy is already established.    

24. (i) Why talk about Zimbabwe?  (ii) I read similar reports from many parts of our own country. Why don’t we discuss that?

Answer:  (i) The President of Zimbabwe is the head of the state of Zimbabwe. In 1987, Robert Mugabe becomes the president and he revise the Constitution to make himself Executive President. President Mugabe is popular but also uses unfair practices in elections. Opposition party workers are harassed, public protest and demonstration against the government are declared illegal, both print and electronic media are controlled by the government. The government has pressurised judges to give verdict in favour of the government. The example of Zimbabwe shows that popular approval of the rulers is necessary in a democracy, but it is not sufficient. A democratic government cannot do whatever it likes, simply because it has won the election. This is the reason for which Zimbabwe is discussed here.

(ii) Our country is democratic and elections are by and large free and fair. However, sometimes we hear reports about use of unfair means, violence and money power in elections. These tactics (methods) are adopted by some candidates with criminal connections or criminal background. However, such cases are decreasing day by day. 

25. This cartoon is from Brazil, a country that has long experience of dictatorship. It is entitled The Hidden Side of Dictatorship’  (i) Which hidden sides does this cartoon depict?  (ii) Is it necessary for every dictatorship to have a hidden side?  (iii) Find this out the dictators discussed in the first chapter and, if possible, about Abacha in Nigeria and Macros in the Philippines. 

Answer:  (i) The hidden side depicted by the cartoon is the brutal side to the dictator. Dictator like Hitler ordered mass killings to eliminate ‘undesirable’ persons like Hitler many dictator killed the innocent people who were against their regime. This evil side of the dictator is shown in this cartoon.

(ii) No, it is not necessary for every dictatorship to have a hidden side. Because, if the dictator really wants to work for the betterment of people, he does not need to have a hidden side.

(iii) (a) The revolt by the army took place in Chile on 11th, September, 1973 under General Augusto Pinochet in which President Salvador Allende was killed. Pinochet became the president of the country and ruled it for the next 17 years. (b) Wojciech Witold Jaruzelski was the last communist leader of Poland who was the head of the state from 1985 to 1990. He resigned from the power after the Polish Round table Agreement in 1989 that led to democratic elections in poland. (c) General Sani Abacha was a Nigerian military dictator and politician. He was the defacto president of Nigeria from 1993 to 1998. His regime was tied to human rights violations and allegations of corruption. He hanged the fomous social activist Ken Saro-Wiwa. He did not allow democratic process like elections in Nigaria He was listed as the world’s fourth most corrupt leader in recent history. (d) Ferdinand Emmanuel Edralin Marcos was the president of the Philippines from 1965 to 1986. He implemented wide-ranging programmes of infrastructure development and economic reform. However, his administration was marred by massive authoritarian, political repression and human rights violations. In the 2004, Global Transparency Report, Marcos appeared in the list of the world’s corrupt leader. He was said to have amassed between $ 5 billion to $ 10 billion in his 21 years as President of Philippines. 

26. Giving an example of Mexico, prove that although having a democratic system, they were not practising democracy.

Answer:  (i) Since independence in 1930, Mexico holds elections every six years to elect their President. (ii) But until 2000, every election was won by a party called PRI. Opposition parties did contest elections, but never managed to win. (iii) The PRI was known to use many dirty tricks to win elections. The PRI spent large sums of money in the campaign for its candidates and booths were shifted from one place to another in the last minute, which made it difficult for the people to cast their votes. 

27. Compare the democratic system in China with Mexico.

Answer:   (i) In China, the elections do not offer people any choice. (ii) They have to choose the ruling party and the candidates approved by it. Mexico: (i) In Mexico, the people seemed to have a choice but practically they did not have any choice. (ii) There was no way that the ruling party could be defeated, even if the people were against it. 

28. Give examples of the countries which do not provide equal rights to vote.

Answer:  There are many examples of countries which do not provide equal rights to vote.   Examples: (i) In Saudi Arabia, women do not have the right to vote. (ii) Estonia has made its citizenship rules in such a way that people belonging to Russian minority find it difficult to get their right to vote. (iii) In Fiji, the electoral system is such that the vote of the Fijian has more value than that of an Indian Fiji. 

29. Give arguments against democracy.

Answer: The arguments against democracy are: (i) Leaders keep changing in a democracy. This leads to instability. (ii) Democracy is all about political competition and power play. There is no scope for morality. (iii) So many people have to be consulted in a democracy that it leads to delays. (iv) Elected leaders do not know the best interest of the people. It leads to bad decision-making. (v) Democracy leads to corruption because it is based on electoral competition. (vi) Ordinary people don’t know what is good for them, so they should not decide anything.

30. Give arguments in favour of democracy.

Answer:  The arguments in favour of democracy are: (i) A democratic government is a better government because it is a more accountable form of government. (ii) Democracy improves the quality of decision-making. (iii) Democracy provides methods to deal with differences and conflicts. (iv) Democracy enhances the dignity of citizens. (v) Democracy is better than other forms of government as it allows rulers to correct its own mistake. 

31. What is democracy? Give examples of non-democratic countries.

Answer:  Democracy is a form of government in which the rulers are elected by the people. Examples of non-democratic countries: (i) The army rulers of Myanmar are not elected by the people. Those who happen to be in control of the army become the rulers of the country. People have no say in the decision making. (ii) Dictators like Pinochet are not elected by the people. (iii) The king of Nepal and Saudi Arabia rule, not because the people have chosen them to do so but because they happen to be born into the royal family. 

32. How does democracy provide a platform to deal with differences and conflicts?

Answer:   In any society people are bound to have differences of opinions and interests. These differences are particularly sharp in a country like ours which has an amazing social diversity. People of our country belong to different regions, speak different languages, practise different religions. So they look at the world very differently and have different preferences. Democracy provides the peaceful solution to this problem. In a diverse country like India, democracy keeps our country together and united. 

33. What have you understood by the term ‘Democracy’?

Answer:   Democracy is a form of government in which rulers are elected by the people. But, this definition is not adequate to define democracy. We need to add up following features: (i) Democracy is a form of government in which rulers elected by the people take all the major decisions. (ii) Elections offer a choice and fair opportunity to the people to   change the current rulers. (iii) This choice and opportunity is available to all the people on an equal basis. (iv) The exercise of this choice leads to a government limited by basic rules of the constitution and citizens rights.   

34. “Democracy is better than other forms of governments because it allows us to correct its own mistakes.” Do you agree with it or not ?  

Answer:   (i) There is no guarantee that mistakes cannot be made in democracy. No form of government can guarantee that. (ii) The advantage in a democracy is that such mistakes cannot be hidden for long. (iii) There is a space for public discussion on these mistakes. And there is a room for correction. (iv) Either the rulers have to change their decision or the rulers can be changed. (v) I believe, this cannot happen in a non-democratic government; so I fully agree that democracy does allow us to correct its own mistakes.

35. State the main features of democracy.

Answer:  The main features of democracy are: (i) In a democracy, the final decision-making power must rest with those elected by the people. (ii) A democracy must be based on free and fair elections, where those currently in power have a fair chance of losing. (iii) In a democracy, each adult citizen must have one vote and each vote must have one value. (iv) A democratic government rules within limits set by the constitutional law and citizens’ rights. (v) Democracy provides a method to deal with differences and conflicts. It enhances the dignity of the citizens. 

36. How can you say that Pakistan was not exercising democracy when General Musharraf was ruling?

Answer:  In Pakistan, General Musharraf led a military coup in October 1999. (i) He overthrew a democratically elected government and declared himself the ‘Chief Executive’ of the country. (ii) Later, he changed his designation to that of a President and in 2002, held a referendum in the country that granted him a five-year extension.   The government in Pakistan, under General Musharraf, cannot be called a democracy because: (i) People may have elected their representatives to the national and provincial assemblies but those elected representatives are not really the rulers. They cannot take the final decisions. (ii) The power to take the final decision rests with the army officials and with General Musharraf and none of them are elected by the people. (iii) Pakistani media, human right organisations and democracy activists said that referendum held by General Musharraf was based on malpractices and fraud. 

37. Giving an example of Zimbabwe, show how laws were made by one single ruler.

Answer:  Since Zimbabwe got independence in 1980, it is being ruled by ZANU-PF which led the freedom struggle. (i) Its leader, Robert Mugabe has been ruling the country since independence. But ZANU-PF won due to unfair practices in elections. (ii) His government has made changes in the constitution several times to increase the power of the President and make him less accountable. (iii) The opposition party workers were harassed and their meetings were disrupted. (iv) Public protests demonstrations are declared illegal. (v) Laws are made to limit the right to criticise the President. (vi) The media has been forced to write and speak in favour of the ruling party. (vii) There are independent newspapers but the government harasses those journalists who go against it. This example of Zimbabwe shows that popular government can be undemocratic. Popular leaders can be autocratic. If we wish to assess a democracy, it is important to look at the elections and how they are fought. 

38. How did Musharraf establish his rule in Pakistan?

Answer:  Musharraf came to power after attempting a military coup. He overthrew a democratically elected government and declared himself the Chief Executive of the country. Later he changed his designation to President and in 2002 held a referendum in the country that granted him a five-year extension. Pakistani media, human right organisations and democracy activists said that the referendum was based on malpractices and fraud. In August 2002, he issued a ‘Legal Framework Order’ that amended the constitution of Pakistan. According to this order, the President can dismiss the national or provincial assemblies. The work of the civilian cabinet is supervised by a National Security Council which is dominated by military officers.  

39. Why Pakistan may not be called a democracy under General Musharraf?

Answer:  Pakistan under General Musharraf should not be called a democracy. People may have elected their representatives to the national and provincial assemblies but those elected representatives are not really rulers. They cannot take the final decisions. The power to take final decision rests with army officials and with General Musharraf, and none of them are elected by the people. This happens in many dictatorships or monarchies. They formally have an elected parliament and government but the real power is with those who are not elected.

40. How did China establish a Communist Government?

Answer:   In China elections are regularly held after every five years for electing the country’s parliament, called National People’s Congress. The National People’s Congress has the power to appoint the President of the country. It has nearly 3,000 members elected from all over China. Some members are elected by the army. Before contesting the elections, a candidate needs the approval of the Chinese Communist Party. Only those who are members of the Chinese Communist Party or eight smaller parties allied to it were allowed to contest elections held in 2002 -2003. The government is always formed by the communist party.

41. What was PRI? What dirty tricks did it play to win elections in Mexico?

Answer:  PRI was a party called Institutional Revolutionary Party of Mexico. All those who were employed in government offices had to attend its party meetings. Even the teachers of government schools used to force parents to vote for the PRI. Media largely ignored the activities of opposition political parties except to criticise them. Sometimes the polling booths were shifted from one place to another in the last minute, which made it difficult for people to cast their votes. The PRI spent a large sum of money in the campaign for its candidates.

42. How did Robert Mugabe establish his dictatorial rule in Zimbabwe, after Independence?

Answer:  After Independence, the country has been ruled by ZANU-PF, the part that led the freedom struggle. Its leader Mugabe had been ruling since Independence. Elections have been held regularly and always won by ZANU- PF. President Mugabe is popular but also uses unfair practices in elections. Over the years, his government has changed the constitution several times to increase the powers of the President and make him less accountable. Opposition party workers are harassed and their meetings disrupted. Public protests and demonstrations against the government are declared illegal. There is a law that limits the right to criticise the President. Television and radio are controlled by the government and give only the ruling party’s version. There are independent newspapers but the government harasses those journalists who go against it. The government has ignored some court judgements that went against it and has pressurised judges. 

43. Under what conditions is a government run after the elections?  

Answer:  A democratic government cannot do whatever it likes simply because it has won the elections. It has to respect some basic rules. In particular it has to provide some guarantees to the minorities. Every major decision has to go through a series of consultations. Every office bearer has certain rights and responsibilities assigned by the constitution and the law. Each of these is accountable not only to the people but also to other independent officials.

44. Why do we need to define democracy accurately?

Answer:  (i) The simple definition of democracy is not adequate. It reminds us that democracy is people’s rule. (ii) But if we use this definition in an unthinking manner, we would end up calling almost every government that holds an election in a democracy. That would be misleading. (iii) Every government in contemporary world wants to be called a democracy, even if it is not so. (iv) That is why we need to carefully distinguish between a government that is a democracy and one that pretends to be one. (v) We can do so by defining it carefully that democracy is a form of government in which the rulers are elected by the people and the final decision-making power must rest with those elected by the people. 

45. Why Pakistan under General Musharraf should not be called a democracy as stated by President Musharraf?

Answer:  Pakistan under General Musharraf should not be called a democracy due to the following reasons: (i) People may have elected their representatives to the national and provincial assemblies but those elected representatives are not really the rulers. (ii) They cannot take the final decisions. (iii) The power to take final decision rests with army officials and with General Musharraf, and none of them are elected by the people. (iv) This happens in many countries,’ where formally they have an elected parliament and government but the real power is with those who are not elected. 

46. In which countries, even today, there is denial of equal right to vote?

Answer:  The principle of universal adult franchise has been accepted almost all over the world, yet there are many instances of denial of equal right to vote. (i) In Saudi Arabia, women do not get the right to vote, they remain mpardah and being told not to interfere in the political matters. (ii) Estonia has made its citizenship rules in such a way that people belonging to Russian minority find it difficult to get the right to vote. (iii) In Fiji, the electoral system is such that the vote of an indigenous Fijian has more value than that of an Indian Fijian.  

47. Once elected by the people, what kind of duties are needed to be performed by the office bearers?

Answer:  (i) A democratic government cannot do whatever it likes, simply because it has won an election. (ii) It has to respect some basic rules. (iii) In particular, it has to extend some guarantees to the minorities. (iv) Every major decision has to go through a series of consultations. (v) Every office bearer has certain rights and responsibilities assigned by the constitution and the law. (vi) Each of these is accountable not only to the people but also to other independent officials. 

Ch#1- Ideological Basis of Pakistan, Class 9th Pak Studies Notes (English) New Course FBISE

by Sajid | Nov 2, 2016 | PAK STUDIES 9TH

[post_title] in PDF Format for FBISE & Other Pakistani Boards

Dear Students, Respectable Teachers and Parents,

In 9th Class Pakistan Studies, the 1st Chapter is Ideological Basis of Pakistan. In this chapter the students will learn about the Importance of Pakistan Studies  as a subject which can help in understanding the origin, creation and development of Pakistan. Definition and Significance of Ideology for a Nation. The concept of sovereignty of Allah in Islam, the guiding principles of Islamic way of life (justice, equality and brotherhood) form the basis of Pakistan’s ideology. Statements of Allama Iqbal and Quaid-e-Azam Muhammad Ali Jinnah defining the ideology of Pakistan (with reference to Allama Iqbal’s 1930 Allahabad Address and Quaid’s address to the Constituent Assembly on August 11,1947). Definition of a Welfare State, Main functions of a welfare state, Difference between an islamic State and Welfare State and responsibilities of an individual and a welfare state. Pakistan’s current status as a welfare state and suggest what further steps need to be taken.

This Chapter has been divided in five parts. Select your desired part from the list given below:

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Download Class 9 Pakistan Studies Notes for both Urdu and English Medium Arts/Science Group Students 2024-25 of FBISE & Punjab Boards. Complete & comprehensive Pakistan Study helping notes according to the updated syllabus for 2024-25 session. The Grade 9 Mutaliya Pakistan notes include 04 units, starting from “Ideological Basis of Pakistan” (پاکستان کی نظریاتی اساس) to “Women’s Empowerment” (خواتین کا بااختیار بنانا)

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• Pak Studies 9th Class Important Questions

Pak Studies

Objective (2021)

(1) M.A. school and college was established by:

(A) Sir Syed Ahmad Khan

(B) Chaudhry Rahmat Ali

(C) Qazi Isa

(D) Mauivi Fazal-ul-Haq

(2) The ideology of Pakistan is based on:

(A) Collective system

(B) Two-Nation Theory

(C) Progressiveness

(D) Islamic Philosophy of Me

(3) ____ was established in 1906.

(A) Congress

(B) Muslim League

(C) Anjuman-i-Himayat-i-Islam

(D) Majlis-e-Ahrar

(4) Realizing the sensitivity of the circumstances. the city which was declared the capital of Pakistan by Quaid-e-Azam was:

(A) Islamabad

(C) Karachi

(D) Faisalabad

(5) India attacked Pakistan in:

(A) September 6, 1965

(B) August 10, 1965

(C) 18t December, 1985

(D) July 15, 1965

(6) Out of total area for the development of any country, the percentage of area for forestation should be:

(7) is situated in the north of Pakistan.

(B) Arabian Sea

(8) Indus river originates from:

(C) Afghanistan

(9) In Arab society, before the advent of Islam in the age of ignorance, girl was:

(C) Buried alive

(D) Respected

(10) The legal age of marriage of girts in Punjab is:

(A) 14 years

(B) 16 years

(C) 18 years

(D) 15 years

Subjective (2021)

Short Questions

• What is meant by “Aqeeda-e-Rissiat”?
• Who was the founder of Shuddhi Movement and what was the aim of this movement?
• What did Quaid-e-Azam say when he inaugurated the State Bank of Pakistan on 1st July, 19487
• Write two objectives of Aligarh Movement.
• What was the “Clause” in 3rd June plan 1947 about province Sindh and Baluchistan?
• Who were the Indian members in Punjab boundary commission constituted under the chairmanship of Radcliffe?
• Why did Quaid-e-Azam oppose Rowlatt Act 1919, declaring it unconstitutional?
• Write four effects of Pak India war 1965.
• When did Zulfigar All Bhutto and Sheikh Mujeeb-u-Rehman meet after 1970 elections and what was the air of this metting?
• Write names of any two glaciers located in Pakistan.
• How can the land pollution be decreased?
• Write briefly the importance of Central Asian Islamic countries for Pakistan.
• What is meant by environmental pollution?
• From which mountain range does Sutlei river originate and at which place it enters Punjab province?
• White the names of Eastern tributaries rivers of the river indus.
• Give briefly introduction of Sameena Baig.
• What Is meant by violence according to World Health Organization?
• What was the role of Fatima Sughra in the Pakistan Movement?

Long Questions

• Write down the fourteen points of Quaid-e-Azam.
• Write down the detail how the climate of Pakistan affects human life.
• Write notes on:

(i) Quaid-e-Azam and Ideology of Pakistan

(ii) Government efforts to address the issue of violence against women in Pakistan

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• Chemistry Important Questions for 9th Class
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• [All in 1 Past papers] 9th class Chemistry – Pakistan Board
• [All in 1 Past papers] 9th class Biology – Punjab Board Pakistan
• [All in 1 past papers] 9th class Urdu – Punjab Board, Pakistan

Related Posts:

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• Past Papers of Pedagogy in Pak Studies
• [PPSC Pakistan] SYLLABUS LECTURER PAK STUDIES SPECIAL EDUCATION DEPARTMENT
• Pak Studies Past Papers
• Chemistry Important Questions for 9th Class - Punjab Board, Pakistan

research topics on alzheimer's disease

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• NATURE INDEX
• 13 March 2024

Researchers call for a major rethink of how Alzheimer’s treatments are evaluated

• Esther Landhuis 0

Esther Landhuis is a science journalist in the San Francisco Bay Area, California.

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Credit: Taj Francis

In January 2023, the US Food and Drug Administration (FDA) approved lecanemab — an antibody medication that decreases β-amyloid protein build-up in the brain — as a treatment for Alzheimer’s disease. Pivotal evidence came from a large, randomized trial of people with early-stage Alzheimer’s , which afflicts around 32 million people worldwide. By the end of that 18-month study 1 , patients in the placebo group scored on average 1.66 points worse than their performance at baseline on a standard dementia test, which assesses cognitive and functional changes over time through interviews with a patient and their caregiver. The mean score of treated participants, by comparison, worsened by 1.21 points — a 27% slowing of cognitive decline.

But is this improvement meaningful for patients and their families?

Nature Index 2024 Health sciences

There are two major categories of drugs used to treat Alzheimer’s disease and other progressive conditions: symptomatic drugs, which treat the symptoms, and disease-modifying drugs, which target the root cause. Donepezil and rivastigmine, for example, are symptomatic drugs that boost the activity of chemicals in the brain to compensate for declines in cognitive and memory function caused by Alzheimer’s disease, but they cannot stop its progression . Lecanemab, developed jointly by Japanese pharmaceutical company Eisai and American biotechnology firm Biogen, targets the underlying issue of amyloid build-up in the brain, and in doing so, could fundamentally change the course of the disease.

An important feature of disease-modifying drugs is that their benefits are cumulative. Studies of patients with multiple sclerosis , for example, have shown the benefits of starting disease-modifying drugs earlier in the course of the disease compared with later, including improved mortality rates and reduced disability in the long term. Being able to quantify how long a disease-modifying drug can delay or halt the progression of Alzheimer’s disease could change how researchers understand — and communicate — its benefits.

In studies of potential disease-modifying drugs for Alzheimer’s disease, there has always been a tension between being able to produce a treatment effect and being able to measure it, says Suzanne Hendrix, statistician and founder of the clinical trials consulting firm Pentara in Salt Lake City, Utah. Clinical trials generally enrol early-stage patients — those with mild cognitive impairment and evidence of brain amyloid — because amyloid-targeting therapies have the best chance of working if given well before the disease takes hold. But in the early stages, patients deteriorate so gradually that it can be difficult to perceive the impact of a disease-modifying drug using standardized tests.

At a scientific meeting in 2009, Hendrix recalls being pulled aside by an executive at Eisai, who told her: “Nobody’s measuring this disease right. Until we measure the most progressive aspects of disease, we’re not going to be able to see treatment effects.”

Source: Institute for Health Metrics and Evaluation; Cummings, J. L., Goldman, D. P., Simmons-Stern, N. R., Ponton, E. Alzheimers Dement. 18 , 469–477 (2022)

Hendrix and other researchers are exploring time-based metrics as a new approach. Savings of time, measured as prolonged quality of life after 18 months of treatment, for example, is “much easier to talk about” than point differences on cognitive and functional scales, says Lars Rau Raket, a statistician at the Copenhagen, Denmark, branch of US pharmaceutical company Eli Lilly. For early-stage Alzheimer’s patients , says Raket, “it’s about how much you can extend the time in the ‘good parts’ — in the milder stages of disease”.

Straight line to time

To come up with a time-based approach, Hendrix and her colleagues pooled parts of several rating scales from standard dementia tests to develop a new tool called that picks up on subtle changes that occur in early Alzheimer’s. By zeroing in on where changes are more pronounced in these early stages, such as a diminished ability to juggle tasks or to recall past events, the team could track the progression of several key features of the disease.

To measure the effectiveness of disease-modifying treatments on these key features as units of time, the researchers used clinical outcomes from placebo and treated participants in a phase II trial of another amyloid-lowering therapy, donanemab . They calculated that over the 76-week duration of the trial, overall disease progression was delayed by 5.2 months.

In a paper published last year 2 , when he was working for Danish firm Novo Nordisk, in a lab just outside Copenhagen, Raket took a similar approach to calculating treatment effects in terms of time. But their methods differed in some ways. Whereas Hendrix’s work focused on calculating time savings across multiple outcomes, Raket used multiple models to calculate time savings for each outcome measure.

The idea of time-based models seems to be gaining traction. They were used as exploratory measures in a phase III trial of donanemab, conducted by Eli Lilly and Company, and published in JAMA last year 3 . Eisai also showed a time-based analysis in a 2022 presentation of its phase III lecanemab data at the Clinical Trials on Alzheimer’s Disease meeting in San Francisco. In those analyses, participants treated with lecanemab took 25.5 months to reach the same degree of worsening on a common dementia test as the placebo group did at 18 months — a time saving of 7.5 months.

Raket says he has been approached by several people in the pharmaceutical industry and academia, and some are working with him to apply the concept to their research. At the 2023 Alzheimer’s Association International Conference in Amsterdam, Raket and his collaborators in the United States, Canada and Europe compared time-based models with conventional statistical approaches for progressive diseases, and analysed how delays in disease progression calculated with time-based methods translate to treatment differences on standard cognitive tests. “I haven’t experienced this kind of interest in my work before,” he says. Raket predicts that an increasing number of trials in the neurodegeneration space will be reporting time-savings estimates in the years to come.

Broad impacts

Beyond Alzheimer’s disease, time-saved models could be applied to other progressive conditions, including Parkinson’s disease and amyotrophic lateral sclerosis (ALS). Cancer and cardiovascular disease studies, which tend to focus on events — delaying relapse or death, or cutting the risk of heart attacks, for instance — are less suited to models that track progression. If, however, heart disease were conceptualized as a gradual worsening of blood pressure or cholesterol over time, and treatment could be shown to slow the rate of deterioration, the time-saved approach could be used to measure the treatment benefit, says Hendrix.

One benefit of time-based methods is that they could help make clinical trials less prone to being skewed by outliers , says Geert Molenberghs, a biostatistician at KU Leuven and Hasselt University, both in Belgium, who collaborates with Hendrix. For example, a small subset of people with early Alzheimer’s disease deteriorate unusually quickly. If these rapid decliners are in the treated group, they could potentially mask a drug benefit, says Molenberghs. The details become “very technical”, he says, but with time-based approaches, these rare individuals “are less influential. They have less capacity to overturn the statistics.”

Time-based metrics could impact broader conversations with health economists and policymakers. “The idea that you could take somebody who’s already in their senior years and keep them functional and not needing 24/7 care — that’s incredibly valuable information for making estimates about the true burden or cost of the disease to caregivers and society,” says John Harrison, chief science officer at Scottish Brain Sciences, a research institute in Edinburgh, Scotland. “It’s a very neat communications tool which feeds into estimates of progression, cost, strategy and, one hopes, legislation and planning.”

There are open questions that might need to be addressed before time-saved models are more widely applied in clinical trials. One is that, although time progresses linearly, not all points on that line are equally meaningful. For example, the anti-amyloid mechanism might only be beneficial in the early stages of Alzheimer’s disease, says Ron Petersen, a neurologist at Mayo Clinic in Rochester, Minnesota. “By the time the person progresses to, say, moderate dementia, modifying amyloid probably isn’t going to make any difference.”

Hendrix is hopeful that the time-saved idea can be further developed and applied to clinical trials in the future, because it could make a big difference in tracking not only how effective new disease-modifying drugs are, but also in helping Alzheimer’s patients and their families to better understand the progression of the disease and how they can plan for it.

Ultimately, as more studies “start focusing on how much time we’ve saved people, all of the effects that we see will be more relevant” to people’s daily lives, Hendrix says.

Nature 627 , S18-S20 (2024)

doi: https://doi.org/10.1038/d41586-024-00756-8

This article is part of Nature Index 2024 Health sciences , an editorially independent supplement. Advertisers have no influence over the content.

Van Dyck, C. H. et al. N. Engl. J. Med. 388 , 9–21 (2023).

Article   PubMed   Google Scholar  

Raket, L. L. Stat. Med. 41 , 5537–5557 (2022).

Sims, J. R. et al. JAMA 330 , 512–527 (2023).

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Comprehensive Review on Alzheimer’s Disease: Causes and Treatment

Alzheimer’s disease (AD) is a disorder that causes degeneration of the cells in the brain and it is the main cause of dementia, which is characterized by a decline in thinking and independence in personal daily activities. AD is considered a multifactorial disease: two main hypotheses were proposed as a cause for AD, cholinergic and amyloid hypotheses. Additionally, several risk factors such as increasing age, genetic factors, head injuries, vascular diseases, infections, and environmental factors play a role in the disease. Currently, there are only two classes of approved drugs to treat AD, including inhibitors to cholinesterase enzyme and antagonists to N -methyl d -aspartate (NMDA), which are effective only in treating the symptoms of AD, but do not cure or prevent the disease. Nowadays, the research is focusing on understanding AD pathology by targeting several mechanisms, such as abnormal tau protein metabolism, β-amyloid, inflammatory response, and cholinergic and free radical damage, aiming to develop successful treatments that are capable of stopping or modifying the course of AD. This review discusses currently available drugs and future theories for the development of new therapies for AD, such as disease-modifying therapeutics (DMT), chaperones, and natural compounds.

1. Introduction

Alzheimer’s disease (AD) (named after the German psychiatric Alois Alzheimer) is the most common type of dementia and can be defined as a slowly progressive neurodegenerative disease characterized by neuritic plaques and neurofibrillary tangles ( Figure 1 ) as a result of amyloid-beta peptide’s (Aβ) accumulation in the most affected area of the brain, the medial temporal lobe and neocortical structures [ 1 ]. Alois Alzheimer noticed a presence of amyloid plaques and a massive loss of neurons while examining the brain of his first patient that suffered from memory loss and change of personality before dying and described the condition as a serious disease of the cerebral cortex. Emil Kraepelin named this medical condition Alzheimer’s disease for the first time in his 8th edition psychiatry handbook [ 2 , 3 ]. Progressive loss of cognitive functions can be caused by cerebral disorder like Alzheimer’s disease (AD) or other factors such as intoxications, infections, abnormality in the pulmonary and circulatory systems, which causes a reduction in the oxygen supply to the brain, nutritional deficiency, vitamin B12 deficiency, tumors, and others [ 4 , 5 ].

The physiological structure of the brain and neurons in ( a ) healthy brain and ( b ) Alzheimer’s disease (AD) brain.

At present, there are around 50 million AD patients worldwide and this number is projected to double every 5 years and will increase to reach 152 million by 2050. AD burden affects individuals, their families, and the economy, with estimated global costs of US$1 trillion annually. At present, there is no cure for Alzheimer’s disease, although there are available treatments that just improve the symptoms [ 6 , 7 ]. The purpose of this review is to give a brief description about AD diagnosis, pathology, causes, and current treatments, and to highlight the recent development of compounds that could prevent or treat AD by targeting several pathogenic mechanisms, such as Aβ and tau aggregation, and misfolding, inflammation, oxidative damage, and others.

2. Alzheimer’s Disease Diagnostic Criteria

A patient suspected to have AD should undergo several tests, including neurological examination, magnetic resonance imaging (MRI) for neurons, laboratory examinations such as vitamin B12, and other tests besides the medical and family history of the patients [ 8 ]. Vitamin (vit.) B12 deficiency has been long known for its association with neurologic problems and increasing risks of AD, according to some studies. A special marker of vit. B12 deficiency is elevated homocysteine levels, which can cause brain damage by oxidative stress, increasing calcium influx and apoptosis. Diagnoses of vit. B12 deficiency can be done by measuring serum vit. B12 level alongside complete blood count and serum homocysteine levels tests [ 9 , 10 ].

In 1984, The National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer’s Disease and Related Disorders Association (ADRDA) formed a work group (NINCDS-ADRDA) to establish a clinical diagnostic’s criteria for Alzheimer’s disease. This criteria includes: (1) probable Alzheimer’s disease, which can be diagnosed by dementia that is confirmed by neuropsychological tests, progressive memory loss, impaired daily-life activity, and other symptoms like aphasia (impairment of a language), apraxia (a motor skills disorder), and agnosia (a loss of perception). All of these symptoms can start from age 40–90, with the absence of any systemic or brain diseases, (2) possible Alzheimer’s disease can be applied in the absence of neurologic, psychiatric disorders, and the presence of another illness like systemic or brain disorder, but they are not the primary cause of dementia, and (3) definite Alzheimer’s disease, that is confirmed by histopathologic confirmation obtained from a biopsy or autopsy [ 11 , 12 ].

In 2011, The National Institute on Aging—Alzheimer’s Association made several changes and updated the 1984 NINCDS-ADRDA criteria for higher specificity and sensitivity in the diagnosis of Alzheimer’s disease. The newly proposed criteria include probable and possible AD dementia for the use in clinical settings and probable or possible AD dementia with pathophysiological evidence for research purposes, in addition to clinical biomarkers. There are two categories of Alzheimer’s disease biomarkers: (a) markers of brain amyloid such as positron emission tomography (PET) and cerebrospinal fluid (CSF), and (b) markers of neuronal injury like cerebrospinal fluid tau, fluorodeoxyglucose (FDG) for metabolic activity, and magnetic resonance imaging (MRI) for atrophy measurement [ 13 , 14 , 15 ].

3. Alzheimer’s Disease’s Neuropathology

There are two types of neuropathological changes in AD which provide evidence about disease progress and symptoms and include: (1) positive lesions (due to accumulation), which are characterized by the accumulation of neurofibrillary tangles, amyloid plaques, dystrophic neurites, neuropil threads, and other deposits found in the brains of AD patients. In addition to (2) negative lesions (due to losses), that are characterized by large atrophy due to a neural, neuropil, and synaptic loss. Besides, other factors can cause neurodegeneration such as neuroinflammation, oxidative stress, and injury of cholinergic neurons [ 16 , 17 , 18 ].

3.1. Senile Plaques (SP)

The senile plaques are extracellular deposits of beta-amyloid protein (Aβ) with different morphological forms, including neuritic, diffuse, dense-cored, or classic and compact type plaques. Proteolytic cleavage enzymes such as β-secretase and γ-secretase are responsible for the biosynthesis of Aβ deposits from the transmembrane amyloid precursor protein (APP) [ 19 , 20 , 21 ]. These enzymes cleave APP into several amino acid fragments: 43, 45, 46, 48, 49, and 51 amino acids, which reach the final forms Aβ40 and Aβ42. There are several types of Aβ monomers, including large and insoluble amyloid fibrils which can accumulate to form amyloid plaques and soluble oligomers that can spread throughout the brain. Aβ plays a major role in neurotoxicity and neural function, therefore, accumulation of denser plaques in the hippocampus, amygdala, and cerebral cortex can cause stimulation of astrocytes and microglia, damage to axons, dendrites, and loss of synapses, in addition to cognitive impairments [ 21 , 22 , 23 ].

3.2. Neurofibrillary Tangles (NFTs)

NFT are abnormal filaments of the hyperphosphorylated tau protein that in some stages can be twisted around each other to form paired helical filament (PHF) and accumulate in neuralperikaryal cytoplasm, axons, and dendrites, which cause a loss of cytoskeletal microtubules and tubulin-associated proteins. The hyperphosphorylated tau protein is the major constituent of NFTs in the brains of AD patients, and its evolution can reflect NFTs morphological stages, which include: (1) pre-tangle phase, one type of NFT, where phosphorylated tau proteins are accumulated in the somatodendritic compartment without the formation of PHF, (2) mature NFTs, which are characterized by filament aggregation of tau protein with the displacement of the nucleus to the periphery part of the soma, and (3) the extracellular tangles, or the ghost NFTs stage, that results from a neuronal loss due to large amounts of filamentous tau protein with partial resistance to proteolysis [ 24 , 25 ].

3.3. Synaptic Loss

A synaptic damage in the neocortex and limbic system causes memory impairment and generally is observed at the early stages of AD. Synaptic loss mechanisms involve defects in axonal transport, mitochondrial damage, oxidative stress, and other processes that can contribute to small fractions, like the accumulation of Aβ and tau at the synaptic sites. These processes eventually lead to a loss of dendritic spines, pre-synaptic terminals, and axonal dystrophy [ 26 ]. Synaptic proteins serve as biomarkers for the detection of synapses loss, and severity, such as neurogranin, a postsynaptic neuronal protein, visinin-like protein-1 (VILIP-1), and synaptotagmin-1 [ 27 , 28 ].

4. The Stages of Alzheimer’s Disease

The clinical phases of Alzheimer’s disease can be classified into (1) pre-clinical or the pre-symptomatic stage, which can last for several years or more. This stage is characterized by mild memory loss and early pathological changes in cortex and hippocampus, with no functional impairment in the daily activities and absence of clinical signs and symptoms of AD [ 1 , 29 , 30 ]. (2) The mild or early stage of AD, where several symptoms start to appear in patients, such as a trouble in the daily life of the patient with a loss of concentration and memory, disorientation of place and time, a change in the mood, and a development of depression [ 30 , 31 ]. (3) Moderate AD stage, in which the disease spreads to cerebral cortex areas that results in an increased memory loss with trouble recognizing family and friends, a loss of impulse control, and difficulty in reading, writing, and speaking [ 30 ]. (4) Severe AD or late-stage, which involves the spread of the disease to the entire cortex area with a severe accumulation of neuritic plaques and neurofibrillary tangles, resulting in a progressive functional and cognitive impairment where the patients cannot recognize their family at all and may become bedridden with difficulties in swallowing and urination, and eventually leading to the patient’s death due to these complications [ 1 , 32 ].

5. Causes and Risk Factors of Alzheimer’s Disease

AD has been considered a multifactorial disease associated with several risk factors ( Figure 2 ) such as increasing age, genetic factors, head injuries, vascular diseases, infections, and environmental factors (heavy metals, trace metals, and others). The underlying cause of pathological changes in Alzheimer’s disease (Aβ, NFTs, and synaptic loss) is still unknown. Several hypotheses were proposed as a cause for AD but two of them are believed to be the main cause: some believe that an impairment in the cholinergic function is a critical risk factor for AD, while others suggest that alteration in amyloid β-protein production and processing is the main initiating factor. However, at present, there is no accepted theory for explaining the AD pathogenesis [ 33 , 34 ].

The risk factors for Alzheimer’s disease.

5.1. Alzheimer’s Disease Hypotheses

5.1.1. cholinergic hypothesis.

In the 1970s, neocortical and presynaptic cholinergic deficits were reported to be related to the enzyme choline acetyltransferase (ChAT), which is responsible for the synthesis of acetylcholine (ACh). Due to the essential role of ACh in cognitive function, a cholinergic hypothesis of AD was proposed. ACh is synthesized in the cytoplasm of cholinergic neurons from choline and acetyl-coenzyme A by the ChAT enzyme and transported to the synaptic vesicles by vesicular acetylcholine transporter (VAChT) ( Figure 3 ). In the brain, ACh is involved in several physiological processes such as memory, attention, sensory information, learning, and other critical functions. Degeneration of the cholinergic neurons was found to take place in AD and to cause alternation in cognitive function and memory loss. Β -amyloid is believed to affect cholinergic neurotransmission and to cause a reduction in the choline uptake and a release of ACh. Studies demonstrated that cholinergic synaptic loss and amyloid fibril formation are related to Aβ oligomers’ neurotoxicity and to interactions between AChE and Aβ peptide. Additional factors also contribute to the progression of AD, such as a reduction in nicotinic and muscarinic (M2) Ach receptors, located on presynaptic cholinergic terminals, and the deficit in excitatory amino acid (EAA) neurotransmission, where glutamate concentration and D-aspartate uptake are significantly reduced in many cortical areas in AD brains. This is in addition to the use of cholinergic receptor antagonists such as scopolamine, which was found to induce amnesia. This effect can be reversed by using compounds that activate acetylcholine formation [ 35 , 36 , 37 ].

The pathway for the synthesis and transportation of acetylcholine between presynaptic and postsynaptic nerve terminals.

As a result, the cholinergic hypothesis is based on three concepts: reduced presynaptic cholinergic markers in the cerebral cortex, severe neurodegeneration of nucleus basalis of Meynert (NBM) in the basal forebrain, which is the source of cortical cholinergic innervation, and the role of cholinergic antagonists in memory decline compared to the agonists, which have the opposite effect [ 38 ].

5.1.2. Amyloid Hypothesis

For decades, it was recognized that abnormal deposition of β-sheets in the central nervous system has a strong correlation with dementia, which led to the concept of the amyloid hypothesis. However, it was found that the amyloid plaques (AP) also deposit in normal healthy brains with aging, which raised the question of whether AP deposition is responsible for AD onset or not? Therefore, in the recent years, alternative hypotheses were proposed for the non-inherited form of AD (NIAD), but at present, the amyloid hypothesis remains the most accepted pathological mechanism for inherited AD (IAD). The amyloid hypothesis suggests that the degradation of Aβ, derived from APP by β- and γ-secretase, is decreased by age or pathological conditions, which leads to the accumulation of Aβ peptides (Aβ40 and Aβ42). Increasing the ratio of Aβ42/Aβ40 induces Aβ amyloid fibril formation, resulting in neurotoxicity and tau pathology induction, and consequently, leading to neuronal cell death and neurodegeneration. AD risk factors and mutations of several genes like APP, PSEN1, and PSEN2 were found to affect Aβ catabolism and anabolism, which rapidly cause an accumulation of Aβ and fast progression of neurodegeneration [ 39 , 40 , 41 ].

5.2. Alzheimer’s Disease Risk Factors

5.2.1. aging.

The most important risk factor in AD is aging. Younger individuals rarely have this disease, and most AD cases have a late onset that starts after 65 years of age [ 42 ]. Aging is a complex and irreversible process that occurs through multiple organs and cell systems with a reduction in the brain volume and weight, a loss of synapses, and ventricles’ enlargement in specific areas accompanied by SP deposition and NFT. Moreover, several conditions might emerge during aging such as glucose hypometabolism, cholesterol dyshomeostasis, mitochondria dysfunction, depression, and cognitive decline. These changes also appear in normal aging, which makes it difficult to distinguish the cases in early AD [ 43 , 44 ]. AD can be divided based on age of onset into early-onset AD (EOAD), the rare form with around 1–6% of cases, in which most of them are familial AD characterized by having more than one member in more than one generation with AD, and ranges from 30–60 or 65 years. The second type is the late-onset AD (LOAD), which is more common with age of onset above 65 years. Both types may occur in people who have a family with a positive history of AD and families with a late-onset disease [ 45 ].

5.2.2. Genetics

Genetic factors were discovered over the years and were found to play a major role in the development of AD. 70% of the AD cases were related to genetic factors: most cases of EOAD are inherited in an autosomal dominant pattern and mutations in the dominant genes such as Amyloid precursor protein (APP) , Presenilin-1 (PSEN-1), Presenilin-2 (PSEN-2) , and apolipoprotein E (ApoE) are associated with AD [ 46 , 47 ].

Herein, we discuss the strong genetic risk factors in AD.

• Amyloid Precursor Protein (APP)

APP is a type I transmembrane protein cleaved by α-, β-, and γ-secretase to release Aβ and other proteins and is encoded by the APP gene on chromosome 21. Thirty mutations have been found in the APP gene in which twenty-five of them are related to AD and cause an accumulation of Aβ with elevated amounts. Meanwhile, there is one protective mutation, A673T, which protects against AD by decreasing Aβ, Aβ40, and Aβ42 secretion [ 48 , 49 ]. All mutations surround the secretase cleavage site, for example, the KM670/671NL mutation in mouse models has shown an increasing level of amyloid plaques in the hippocampus and cortex with no NFTs. A673V, D678H, D678N, E682K, and K687N mutations have shown cortical atrophy, whereas E682K has shown hippocampal atrophy. Neuropathological reports for the A673V mutation demonstrated a presence of NFTs and Aβ, activation of microglia and astrocytes, and neuronal loss, compared to the rest of the mentioned mutations, which show no change in the intracellular Aβ according to neuropathological reports [ 48 , 50 ]. Other mutations such as T714I, V715A, V715M, V717I, V717L, L723P, K724N, and I716V affect the γ-secretase cleavage site and cause an increase in the Aβ42/Aβ40 ratio, while E693G, E693K, D694N, and A692G mutations affect the α-secretase cleavage site and cause polymorphic aggregates with the ability to disrupt bilayer integrity. Also, the E693delta is a deletion mutation that enhances the formation of synaptotoxic Aβ [ 51 , 52 ].

• Presenilin-1 (PSEN-1) and Presenilin-2 (PSEN-2)

PSEN1 and PSEN2 genes are also the autosomal dominant form of EOAD located on chromosomes 14 and 1, respectively. PSEN-2 and PSEN-1 are homologous, with 67% similarity, with a difference in the N -terminus and the hydrophilic region. Mutation in PSEN1 gene is more common, with more than 200 mutations, while a rare form with less than 40 mutations was identified in the PSEN2 gene [ 53 , 54 ].

PSEN1 is a core protein that activates the γ-secretase complex and plays an important role in the production of Aβ from APP. Knockout studies of PSEN1 showed synaptic dysfunction and memory impairment in mice, which indicate its essential role in maintaining memory and neurons [ 51 ]. PSEN1 mutations are simple ones which include single amino acid substitution, and severe mutation can result from the substitutions of two amino acids [ 55 ]. Mutations in the PSEN1 gene increase the ratio of Aβ42/Aβ40 by decreasing Aβ40 levels. The results obtained by Sun et al. study demonstrated that C410Y or L435F mutations in PSEN1 knock-in mice increased the Aβ42/Aβ40 ratio due to a greater reduction in Aβ40 [ 56 ].

In contrast, PSEN-2 mutations are rare and play a minor role in Aβ production. Any mutation in PSEN-2 might have a severe effect on the Aβ 42/40 ratio, causing familial AD in the presence of normal PSEN-1 alleles. Some of the PSEN-2 mutations cause a significant increase in γ-secretase activity with an elevation in the Aβ-42 and Aβ 42/40 ratio level, such as N141I, T122P, M239V, and M239I, while others are rare polymorphisms and have no effect on Aβ-42, -40, and Aβ 42/40 ratio levels and are not considered as pathogenic mutations [ 53 , 57 ].

• Apolipoprotein E (ApoE)

ApoE protein is a glycoprotein expressed highly in the liver and brain astrocytes and some microglia and serves as a receptor-mediated endocytosis ligand for lipoprotein particles like cholesterol, which is essential for myelin production and normal brain function. The ApoE gene located on chromosome 19 has three isoforms, ApoE2, ApoE3, and ApoE4, due to single-nucleotide polymorphisms (SNPs) which cause changes in the coding sequence. The ApoEε4 allele is a strong risk factor for both EOAD and LOAD compared to ApoEε2 and ApoEε3 alleles that are associated with a lower risk and protective effect, respectively [ 58 ]. ApoEε4 plays an important role in Aβ deposition as a senile plaque and causes cerebral amyloid angiopathy (CAA), which is known as a marker for AD [ 59 ]. ApoEε4 was also shown to be associated with vascular damage in the brain, which leads to AD pathogenesis [ 60 ].

• ATP Binding Cassette Transporter A1 (ABCA1)

Adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) is part of a large ABC transporters family that regulate cholesterol efflux in the circulation, like apolipoproteins-AI (ApoAI), and into the brain, like ApoE. In addition, ABCA1 maintains the stability of ApoE lipidation and serves as a mediator for high-density lipoprotein (HDL) generation, which reflects its role in atherosclerosis and cardiovascular diseases. Studies on the AD mice model showed that ABCA1 deficiency increases amyloid plaques and eliminates the lipidation of ApoE [ 61 ]. In humans, a mutation in ABCA1 results in Tangier disease, which is characterized by low levels of high-density lipoprotein (HDL) and ApoAI in plasma, accumulation of cholesterol in tissues, and AD pathogenesis [ 62 ].

• Clusterin Gene (CLU) and Bridging Integrator 1 ( BIN1 )

In contrast to PSEN1 , PSEN2 , and APP mutations, which result in familial or EOAD, clusterin ( CLU) and Bridging Integrator 1 ( BIN1 ) genes are novel risk factors for LOAD. In 2009, Genome-Wide Association Studies (GWAS) identified the CLU gene located on chromosome 8, which is upregulated in the cortex and hippocampus of AD brains, in addition to AD cerebrospinal fluid (CSF) and plasma, which make the CLU a promising biomarker for AD. The CLU may play a protective role by interacting with Aβ and promoting its clearance, or a neurotoxic role by reducing Aβ clearance. The Aβ ratio values determine whether the CLU role is neuroprotective or neurotoxic [ 63 ].

BIN1 is a Bin-Amphiphysin-Rvs (BAR) adaptor protein that is involved in the production of membrane curvature and other endocytosis cellular functions. BIN1 has several isoforms: some are found in the brain, where they interact with different proteins such as clathrin, synaptojanin, and amphiphysin 1, and others in which they regulate synaptic vesicle endocytosis. Recently, BIN1 was recognized as the second most important risk factor for LOAD after ApoE, where it plays a role in Aβ production and as a tau and NFT pathology modulator [ 64 , 65 ].

• Evolutionarily Conserved Signaling Intermediate in Toll pathway (ECSIT)

A significant accumulation of Aβ in AD brains increases protein oxidation, which reflects the critical role of mitochondria in Aβ cytotoxicity and AD pathogenesis. Evolutionarily conserved signaling intermediate in Toll pathway (ECSIT) gene is located on chromosome 19 and is associated with increasing the risk of AD. ECSIT encodes the adapting protein that functions as a cytoplasmic and signaling protein and is responsible for stabilizing the mitochondrial respiratory complex. Moreover, the adaptor protein is involved in the activation of nuclear factor (NF)-κB, interferon regulatory factors (IRFs), and activating protein-1. Also, it is involved in coupling immune toll-like receptor (TLR), homeostatic bone morphogenetic pathway (BMP), and transforming growth factor-beta (TGF-b) pathways [ 66 , 67 ].

ECSIT interacts with mitochondrial proteins such as Lon protease homolog (LONP1) and glutaryl-CoA dehydrogenase (GCDH), which are involved in intra-mitochondrial proteolysis and redox signaling respectively, followed by interactions with AD seed nitric oxide synthase (NOS3). Moreover, studies have shown certain interactions of ECSIT with the AD genes ApoE , PSEN-1 , and PSEN-2 . These interactions support the role of ECSIT as a molecular link in oxidative stress, inflammation, and mitochondrial dysfunction in AD [ 66 , 68 ].

• Estrogen Receptor Gene (ESR)

AD affects both women and men, but nearly two-thirds of AD cases are women. Several studies have shown that women with AD experience worse mental deterioration than men. Additionally, on the genetic level, some genes’ variation, like the ApoE4 allele, significantly increases AD risk in women compared to men. Other studies documented that AD risk in women is associated with the loss of ovarian hormones during menopause due to the fact that estrogen regulates several activities in the brain, such as neurotransmission, neural development, survival, protection against oxidative stress, reduction of Aβ peptide levels, and attenuation of tau hyperphosphorylation. The estrogen activity is mediated through estrogen receptors (ERs) (intracellular, transmembrane, and membrane-bound ERs). The two major subtypes of these receptors are ERα and Erβ, which are encoded by two distinct genes and are located on chromosome 6 and 14, respectively. ERα receptor is found in the hypothalamus and amygdala, whereas ERβ receptors are in the hippocampus and cortex. Single nucleotide polymorphisms (SNPs) in ERβ and ERα genes may affect exogenous estrogen in older women and influence cognitive aging. PvuII (rs9340799) and Xbal (rs223493) are examples of SNPs found in ERα and are associated with AD and cognitive impairment. Also, several SNPs in ERβ have been proven to increase the risk of AD in women [ 69 , 70 , 71 , 72 ].

• Other Genes

Other genes’ polymorphism associated with increasing the risk of AD include vitamin D receptor (VDR) gene polymorphism, which affects the affinity of vitamin D to its receptor and may cause neurodegenerative diseases and neuronal damage [ 73 ]. Moreover, epigenetic factors like DNA methylation, histone, and chromatin modifications were demonstrated to be involved in AD [ 33 , 74 ].

5.2.3. Environmental Factors

Aging and genetic risk factors cannot explain all cases of AD. Environmental risk factors including air pollution, diet, metals, infections, and many others may induce oxidative stress and inflammation and increase the risk for developing AD. Herein, we report the most important environmental factors and their relationships with AD [ 75 , 76 ].

• Air Pollution

The air pollution is characterized by modifying the nature of the atmosphere through the introduction of chemical, physical, or biological pollutants. It is associated with respiratory and cardiovascular diseases and recently, its association with AD was documented. Six air pollutants have been defined by National Ambient Air Quality Standards (NAAQSs) in the USA as a threat to human health, including ozone (O 3 ), nitrogen oxides (NO x ), carbon monoxide (CO), particulate matter (PM), sulfur dioxide (SO 2 ), and lead. Studies on animals and cellular models have shown that an exposure to high levels of air pollution can result in a damage to the olfactory mucosa and bulb, in addition to the frontal cortex region, similar to that observed in AD. In individuals exposed to air pollutants, there is a link between oxidative stress, neuroinflammation, and neurodegeneration, with the presence of hyper-phosphorylated tau and Aβ plaques in the frontal cortex. The air pollution can cause an increase in Aβ 42 formation, accumulation, and impaired cognitive function [ 77 , 78 ].

In recent years, the number of studies on the role of nutrition in AD have been increased. Several dietary supplements such as antioxidants, vitamins, polyphenols, and fish were reported to decrease the risk of AD, whereas saturated fatty acids and high-calorie intake were associated with increasing the risk of AD [ 79 ]. The food processing causes degradation of heat-sensitive micronutrients (e.g., vitamin C and folates), loss of large amounts of water, and formation of toxic secondary products (advanced glycation end products, AGEs) from non-enzymatic glycation of free amino groups in proteins, lipids, and nucleic acids. The toxic effect of AGEs is referred to as their ability to induce oxidative stress and inflammation by modifying the structure and function of the cell surface receptors and body proteins. Different studies demonstrated that elevated AGEs serum level is associated with cognitive decline and progression of AD. The AGE receptor (RAGE) is located in different places within the body, including microglia and astrocytes, and was established to be overexpressed in the brain of AD patients and serve as a transporter and a cell surface receptor for Aβ [ 80 ]. Malnutrition is another risk factor for AD. Deficiency in nutrients such as folate, vitamin B12, and vitamin D may cause a decrease in cognitive function, in addition to the fact that patients with AD suffer from problems associated with eating and swallowing, which may increase the risk of malnutrition [ 81 ].

Metals are found in nature and biological systems and can be divided into bio-metals that have a physiological function in living organisms (e.g., copper, zinc, and iron), and toxicological metals which do not possess any biological function (e.g., aluminum and lead) [ 82 ]. Aluminum is used significantly in the industries such as processed foods, cosmetics, medical preparations, medicines, and others. In the body, aluminum is bound to plasma transferrin and to citrate molecules that can mediate the transfer of aluminum to the brain. Studies demonstrated that Al accumulates in the cortex, hippocampus, and cerebellum areas, where it interacts with proteins and causes misfolding, aggregation, and phosphorylation of highly phosphorylated proteins like tau protein, characteristic of AD [ 83 ]. Lead competes with the binding site of bio-metals like calcium and can cross the blood–brain barrier (BBB) rapidly, where it can modify neural differentiation and synaptogenesis and cause severe damage. Studies revealed that an acute exposure to lead was associated with AD and caused an increase of β-secretase expression and Aβ accumulation. Cadmium is a carcinogenic water-soluble metal that can cross the BBB and cause neurological diseases like AD. Results have demonstrated that Cadmium ions are involved in the aggregation of Aβ plaques and the self-aggregation of tau in the AD brain. The data accumulated on metals support the notion that they are among the risk factors involved in the development of AD [ 84 ].

Chronic infections to the central nervous system (CNS) can cause an accumulation of Aβ plaques and NFT, therefore, they are included among the risk factors in AD. Studies by Dr. Itzhaki showed that the DNA of herpes simplex virus (HSV-1) was found in patients with ApoE-ε4 allele carriers, which explains the high risk for developing AD. HSV-1 can replicate in the brain, which can result in the activation of the inflammatory response and an increase in Aβ deposition, resulting in damage to neurons and gradual development of AD. On the other hand, the study results by Miklossy and Balin’s have revealed the role of chronic bacterial infections in AD. For example, syphilitic dementia caused by spirochete bacteria ( Treponema pallidum ), which are accumulated in the cerebral cortex, produced lesions similar to neurofibrillary tangles, which led to devastating neurodegenerative disorders. Besides, Chlamydia pneumonia bacterium can trigger late-onset AD by activation of astrocyte and cytotoxic microglia, disrupt calcium regulation and apoptosis, resulting in deterioration of cognitive function, and increase the risk of AD [ 85 , 86 , 87 ].

5.2.4. Medical Factors

Several risk factors are related to the development of Alzheimer’s disease. Adding to this list, older people with AD usually have medical conditions such as cardiovascular disease (CVD), obesity, diabetes, and others. All of these conditions are associated with increased risk of AD [ 88 , 89 ].

• Cardiovascular Disease (CVDs)

CVDs are recognized as an important risk factor for AD, such as the stroke that is associated with increased risk of dementia due to a neural tissue loss, which enhances degenerative effect and influences amyloid and tau pathology. Atrial fibrillation also causes embolisms which leads to stroke and a decrease in memory and cognitive functions. Moreover, heart failure affects the pumping function of the heart and results in insufficient blood supply to the body and hypo-perfusion of the brain that leads to hypoxia and neural damage. The coronary heart disease’s hypothesis indicates that atherosclerosis, peripheral artery disease, hypo-perfusion, and emboli are all related to increased risk of AD. Hypertension is associated with thickening of vessel walls and narrowing of the lumen which reduce the cerebral blood flow, and in chronic cases, it may cause cerebral edema, which all participate as risk factors for AD and CVD. The CVD is a modifiable risk factor and by focusing on its relationship with AD, a pathway to prevent and delay the disease can be obtained [ 89 , 90 ].

• Obesity and Diabetes

Obesity is a term used for too much body fat in individuals due to consuming more calories than they burn and can be calculated by using the body mass index (BMI). Increasing the body fat is associated with a decreased brain blood supply which promotes brain ischemia, memory loss, and vascular dementia. The obesity, unhealthy diet, and other factors can cause impaired glucose tolerance (IGT) or diabetes, which is characterized by hyperglycemia that affects peripheral tissues and blood vessels. Chronic hyperglycemia can induce cognitive impairment as a result of increasing amyloid-beta accumulation, oxidative stress, mitochondrial dysfunction, and neuroinflammation. Obesity is characterized by increasing pro-inflammatory cytokines secretions from adipose tissue, which stimulate macrophages and lymphocytes and eventually lead to local and systemic inflammation. This inflammation promotes insulin resistance, hyperinsulinemia, and as a consequence, hyperglycemia. Obesity is a well-known risk factor for type 2 diabetes, CVDs, and cancer, which are identified as risk factors for dementia and AD. The brain inflammation causes an increase in microglia and results in reduced synaptic plasticity and impaired neurogenesis. Microglia can affect insulin receptor substrate 1 (IRS-1) and block intracellular insulin signaling, which has an important role in neural health. Therefore, alteration in insulin action can result in Aβ accumulation and reduce the tau protein degradation associated with AD [ 91 , 92 , 93 , 94 ].

6. Treatment

Currently, Alzheimer’s disease cases worldwide are reported to be around 24 million, and in 2050, the total number of people with dementia is estimated to increase 4 times. Even though AD is a public health issue, as of now, there is only two classes of drugs approved to treat AD, including inhibitors to cholinesterase enzyme (naturally derived, synthetic and hybrid analogues) and antagonists to N -methyl d -aspartate (NMDA). Several physiological processes in AD destroy Ach-producing cells which reduce cholinergic transmission through the brain. Acetylcholinesterase inhibitors (AChEIs), which are classified as reversible, irreversible, and pseudo-reversible, act by blocking cholinesterase enzymes (AChE and butyrylcholinesterase (BChE)) from breaking down ACh, which results in increasing ACh levels in the synaptic cleft [ 95 , 96 , 97 ]. On the other hand, overactivation of NMDAR leads to increasing levels of influxed Ca 2+ , which promotes cell death and synaptic dysfunction. NMDAR antagonist prevents overactivation of NMDAR glutamate receptor and hence, Ca 2+ influx, and restores its normal activity. Despite the therapeutic effect of these two classes, they are effective only in treating the symptoms of AD, but do not cure or prevent the disease [ 98 , 99 ]. Unfortunately, only a few clinical trials on AD have been launched in the last decade and their outcome was a big failure. Several mechanisms have been proposed to understand AD pathology in order to modify its pathway and develop successful treatments, which include abnormal tau protein metabolism, β-amyloid, inflammatory response, and cholinergic and free radical damage [ 30 , 100 ]. On the other hand, most AD modifiable risk factors such as cardiovascular or lifestyle habits can be prevented without medical intervention. Studies showed that physical activity can improve the brain health and reduce AD by activating the brain vascularization, plasticity, neurogenesis, and reducing inflammation by decreasing Aβ production, which all result in improving cognitive function in older people. Moreover, the Mediterranean diet (MD), intellectual activity, and higher education all may reduce the progression of AD and memory loss and increase the brain capacity and cognitive functions. Several studies revealed that multi-domain intervention which includes lifestyle (diet, exercise, and cognitive training), depression of AD symptoms, and controlling cardiovascular risk factors, can increase or maintain cognitive function and prevent new cases of AD in older people [ 101 ]. Herein, we summarize the currently available drugs and theories for the development of new therapies for AD.

6.1. Symptomatic Treatment of AD

6.1.1. cholinesterase inhibitors.

According to the cholinergic hypothesis, AD is due to the reduction in acetylcholine (ACh) biosynthesis. Increasing cholinergic levels by inhibiting acetylcholinesterase (AChE) is considered one of the therapeutic strategies that increases cognitive and neural cell function. AChEIs are used to inhibit acetylcholine degradation in the synapses, which results in continuous accumulation of ACh and activation of cholinergic receptors. Tacrine (tetrahydroaminoacridine) ( 1, Figure 4 ) was the first FDA (Food and Drug Administration)-approved cholinesterase inhibitor drug for the treatment of AD, which acts by increasing ACh in muscarinic neurons, but it exited the market immediately after its introduction due to a high incidence of side effects like hepatotoxicity and a lack of benefits, which was observed in several trials. Later on, several AChEIs were introduced, such as donepezil ( 2 , Figure 4 ), rivastigmine ( 3 , Figure 4 ), and galantamine ( 4 , Figure 4 ), and are currently in use for the symptomatic treatment of AD [ 34 , 97 , 102 , 103 ]. Another strategy that may help in the treatment of AD is increasing choline reuptake and as a result, increasing acetylcholine synthesis at the presynaptic terminals. This can be achieved by targeting choline transporter (CHT1) which is responsible for supplying choline for the synthesis of ACh. Developing drugs that are capable of increasing CHT1 at the plasma membrane may become the future therapy of AD [ 36 ].

The chemical structures of approved drugs for symptomatic treatment of AD (tacrine 1 , donepezil 2 , rivastigmine 3 , galantamine 4 , and memantine 5 ) and disease-modifying compounds that entered clinical trials (semagacestat 6 , avagacestat 7 , tarenflurbil 8 , lanabecestat 9 , verubecestat 10 , atabecestat 11 , umibecestat 12 , methylene blue 13 , tideglusib 14 , and saracatinibin 15 ).

Donepezil ( 2 , Figure 4 ) is an indanonebenzylpiperidine derivative and a second generation of AChEIs and is considered the leading drug for AD treatment. Donepezil binds to acetylcholinesterase reversibly and inhibits acetylcholine hydrolysis, which leads to a higher concentration of ACh at the synapses. The drug is well-tolerated with mild and transient cholinergic side effects which are related to the gastrointestinal and nervous systems. It should be noted that donepezil is used to treat symptoms of AD such as improving cognition and behavior without altering the AD progression [ 104 , 105 , 106 ].

• Rivastigmine

Rivastigmine ( 3 , Figure 4 ) is a pseudo irreversible inhibitor of AChE and butyrylcholinesterase (BuChE) that acts by binding to the two active sites of AChE (anionic and estearic sites), which results in preventing ACh metabolism. BuChE is found mostly in glial cells with only 10% of AChE activity in the normal brain, whereas in the AD brain, its activity is increased to 40–90%, while ACh activity is reduced simultaneously, which suggests that BuChE action may indicate a moderate to severe dementia. Rivastigmine dissociates more slowly than AChE, which is why it is called a pseudo-irreversible, and it undergoes metabolism at the synapse by AChE and BuChE. The drug is used in mild to moderate AD cases. It improves cognitive functions and daily life activities. Oral administration of the drug is associated with adverse effects such as nausea, vomiting, dyspepsia, asthenia, anorexia, and weight loss. In many cases, these side effects are the main reason behind stopping taking the medicine, however, they can be settled down in time and consequently, the drug becomes more tolerated. Rivastigmine can be delivered by transdermal patches for controlled and continuous delivery of the drug through the skin, with enhanced tolerability and caregiver satisfaction. Also, the patches can deliver a lower dosage compared to pills, which results in reduced side effects. Most AD patients suffer from memory loss and swallowing problems which affect their compliance in administering oral drugs at regular intervals. Therefore, the use of transdermal patches is the most appropriate method for delivering the drug in AD patients [ 107 , 108 , 109 , 110 ].

• Galantamine (GAL)

Galantamine ( 4 , Figure 4 ) is considered a standard first-line drug for mild to moderate AD cases. GAL is a selective tertiary isoquinoline alkaloid with a dual mechanism of action in which it acts as a competitive inhibitor of AChE and can bind allosterically to the α-subunit of nicotinic acetylcholine receptors and activate them. GAL can improve behavioral symptoms, daily life activities, and cognitive performance with good efficacy and tolerability, similar to other AChE inhibitors. Several delivery systems were developed to improve the drug delivery to the brain: Wahba et al. attached GAL to ceria-containing hydroxyapatite particles for selective delivery of the drug to the affected regions in the brain. Misra et al. and Fornaguera et al. used solid-lipid nanoparticles and nano-emulsification approaches respectively, to carry GAL hydrobromide. The results of these studies demonstrated a promising strategy for safe delivery of the drug. Hanafy et al. developed nasal GAL hydrobromide/chitosan complex nanoparticles which showed good pharmacological efficacy, while Woo et al. utilized the patch system as a carrier for a controlled release dosage form of the drug [ 111 , 112 , 113 , 114 ].

6.1.2. N -methyl d -aspartate (NMDA) Antagonists

NMDAR is believed to have a dominant role in the pathophysiology of AD. NMDAR stimulation results in Ca 2+ influx which activates signal transduction and as a consequence, it triggers gene transcription essential for the formation of a long-term potentiation (LTP), which is important for synaptic neurotransmission, plasticity, and memory formation. Over-activation of NMDARs causes an abnormal level of Ca 2+ signaling and overstimulation of glutamate, which is the primary excitatory amino acid in the CNS, which results in excitotoxicity, synaptic dysfunction, neuronal cell death, and a decline in cognitive functions. Several NMDAR uncompetitive antagonists have been developed and entered clinical trials, however, most of them failed due to low efficacy and side effects. Memantine ( 5 , Figure 4 ) is the only approved drug in this category to treat moderate to severe AD; in addition, other NMDAR uncompetitive antagonist compounds are being developed, such as RL-208 (3,4,8,9-tetramethyltetracyclo [4.4.0.0 3,9 .0 4,8 ]dec-1-yl)methylamine hydrochloride), a polycyclic amine compound that may possess a promising therapeutic effect in age-related cognitive problems and AD [ 115 , 116 , 117 ].

Memantine ( 5 , Figure 4 ) is a low-affinity uncompetitive antagonist of the NMDAR, a subtype of glutamate receptor that prevents over-activation of the glutaminergic system involved in the neurotoxicity in AD cases. Memantine is used for the treatment of moderate to severe AD alone or in combination with AChEI. The drug is safe and well-tolerated, it blocks the excitatory receptor without interfering with the normal synaptic transmission due to memantine’s low affinity, where it is displaced rapidly from NMDAR by high concentrations of glutamate, thus avoiding a prolonged blockage. The latter is associated with high side effects, especially on learning and memory [ 99 , 118 ].

6.2. Promising Future Therapies

6.2.1. disease-modifying therapeutics (dmt).

Disease-modifying treatment or therapy (DMT) alter the progression of AD by working on several pathophysiological mechanisms. This is in contrast to symptomatic therapy which works on improving the cognitive functions and decreasing symptoms such as depression or delusions without affecting or modifying the disease. DMTs, either immunotherapies or small molecules, are administrated orally and are being developed to prevent AD or decrease its progression. Several DMTs have been developed and entered the clinical trials, such as AN-1792, a synthetic Aβ peptide (human Aβ 1–42 peptide of 42-amino acids with the immune adjuvant QS-21) and the first active immunotherapy for AD which entered phase II clinical trials and discontinued due to a meningoencephalitis side effect in 6% of the patients. Other drugs were also developed and failed in the clinical trials, including the anti-Aβ antibody (solanezumab and bapineuzumab), γ-Secretase inhibitors (semagacestat 6 , avagacestat 7 , and tarenflurbil 8 ) ( Figure 4 ) and β-secretase inhibitors (BACE) (Lanabecestat 9, verubecestat 10 , and atabecestat 11 ) ( Figure 4 ). DMTs failures are due to several factors, such as starting therapy too late, giving treatment for the wrong main target, use of inappropriate drug doses, and misunderstanding of the pathophysiology of AD. Several immunotherapies described in Table 1 have been developed over decades, including: CAD106, an active Aβ immunotherapy that induces Aβ antibodies in animal models and consists of multiple copies of Aβ1–6 peptide coupled to Qβ coat protein, a virus-like particle, and is still in clinical trials, and CNP520 (umibecestat, 12 ) ( Figure 4 ), a small molecule that inhibits beta-scretase-1 (BACE-1) and therefore inhibits Aβ production. CNP520 was found to reduce Aβ plaque deposition and Aβ levels in the brain and CSF in rats, dogs, and healthy adults ≥ 60 years old, and is still under clinical trials. Furthermore, aducanumab, gantenerumab, and crenezumab are all human Aβ monoclonal antibody that bind with high affinity to aggregated Aβ, and they are still under study in the clinical phases with other DMTs described in Table 1 [ 6 , 119 , 120 , 121 , 122 , 123 , 124 ].

Disease modifying agents for the treatment of Alzheimer’s disease in clinical trials.

Another class targeting the α-secretase enzyme was developed and has been considered as therapeutic agents. α-secretase modulators or activators stimulate the cleavage of APP. There is little knowledge about the activation pathway, but research assumes that it is promoted by the phosphatidylinositol 3-kinase (PI3K)/Akt pathway or by γ-aminobutyric acid (GABA) receptor signaling. Targeting these pathways may give potential therapeutic agents for AD [ 6 ].

In addition to the anti-amyloid agents, the tau aggregation inhibitors are another promising DMT. The tau is a biomarker for neurofibrillary tangles (NFT) in AD and naturally modulates microtubule stability, signaling pathways, and axonal transport. A modification in tau conformation results in toxic aggregation. Therefore, the prevention of tau aggregation becomes an interesting approach for drug discovery to reduce AD progression. Studies in mice have shown that tau oligomers cause mitochondrial damage, disruption of neuronal signaling, synaptic loss, and memory impairment. Disease-modifying therapeutics (DMT) like small molecules can be used to inhibit the initial step in the tau aggregation and thereby reduce its accumulation. Methylene blue ( 13 , Figure 4 ) is a blue dye that inhibits the tau aggregation and entered phase II clinical trials to treat mild to moderate AD. Upon administration of the drug, the color of the urine becomes blue, which indicates a lack of binding, and because of that, the study was highly criticized. Other approaches suggest that an inhibition of specific kinases such as glycogen synthase kinase 3 (GSK3β) can inhibit tau hyperphosphorylation and block tau deposition. Examples of these entities include tideglusib ( 14 , or NP-031112 (NP-12), Figure 4 ), a thiazolidinedione-derived compound, lithium, pyrazolopyridines, pyrazolopyrazines, sodium valproate, and others. Another protein kinase inhibitor is saracatinib (AZD0530) ( 15 , Figure 4 ), which acts by inhibiting tyrosine kinase and has shown good results in improving memory in transgenic mice and is currently in phase II trials [ 125 , 126 , 127 ]. Davidowitz et al. utilized the hatu mouse model of tauopathy to study the efficacy of a lead small molecule in preventing tau accumulation. The study results demonstrated a significant reduction in tau levels and its phosphorylated form levels, which indicates the ability to inhibit the entire pathway of the tau aggregation by using an optimized lead compound [ 128 ].

6.2.2. Chaperones

Protein misfolding caused by mutations or environmental factors results in aggregations that are toxic, and their accumulation causes neurodegenerative disorders like AD. Naturally, cells develop protein quality control (PQC) systems that inhibit protein misfolding before exerting their toxic effects. With age, this balance is altered and the misfolded shapes overwhelm the PQC system, which in turn activates the unfolded protein response (UPR) that stops the protein synthesis and increases chaperone production. Generally, the cells in humans have proteins that are responsible for other proteins to function and arrive to their destination in the cell. These proteins are called “chaperones”. Chaperones are involved in protein folding and improvement of the PQC system efficiency. Therefore, it is considered a promising candidate for treating neurodegenerative diseases. It can be classified into three groups: (1) molecular chaperones, which are proteins that assist other nonnative proteins in their folding or unfolding, like overexpression of heat shock proteins (Hsps) that serve as neuroprotective agents, (2) pharmacological chaperones, which are low molecular weight compounds (enzymes or receptor-ligand or selective binding molecules) that induce refolding of proteins, stabilize their structure, and restore their function, and (3) chemical chaperones, also low molecular weight compounds, which are divided into two groups, osmolytes and hydrophobic compounds. The members in these two groups have no specific mechanism of action and need high concentrations to exert their therapeutic effects [ 129 ].

• Heat Shock Proteins (Hsps)

The causes for most neurodegenerative diseases are protein misfolding and aggregation, which lead to cell death. The molecular chaperone can be intracellular, such as in the case of heat shock proteins (e.g., Hsp40, Hsp60, Hsp70, Hsp90, Hsp100, and Hsp110), and extracellular, such as clustering and alpha-macroglobulin. HSPs play an essential role in the protein folding process and protect cells from harmful stress-related events. There are two families of Hsps: (a) classic Hsps that possess an ATP-binding site with a molecular weight of 60 kD or more. This family includes Hsp100, Hsp90, Hsp70, and Hsp60, and (b) the small Hsps such as αB-crystalline, Hsp27, Hsp20, HspB8, and HspB2/B3 that lack ATP-binding site, with a molecular weight of 40 kD or less. These proteins can assist other Hsps in their refolding function. Failure of these mechanisms can lead to oxidative stress, mitochondrial dysfunction, and many other conditions that cause damage, a loss of neurons, and a progression of neurodegenerative diseases. Different HSPs can block the aggregation process of misfolded proteins, like amyloidogenic proteins (Aβ and tau), and promote their degradation [ 130 , 131 ].

Hsp60 plays an important role in mitochondrial protein folding. Its role in AD is not clear, some believe that the protein has a protective role and others think it has a harmful effect where it can be over-expressed by activated microglia, which increases pro-inflammatory factors such as toll-like receptor 4 (TLR-4) that stimulate neuronal cell death. Therefore, inhibiting activated microglia and Hsp60 expression is a promising strategy for preventing neurodegenerative diseases. Examples of compounds that inhibit Hsp60 are mizoribine (Immunosuppressant) ( 16 , Figure 5 ) and pyrazolopyrimidine EC3016 ( 17 , Figure 5 ). Both compounds act by blocking ATPase activity of Hsp60 and inhibiting protein folding. On the other hand, avrainvillamide, a fungal metabolite ( 18 , Figure 5 ), and epolactaene, a bacterial metabolite ( 19 , Figure 5 ), act by binding to the Hsp60′s cysteine residues and inhibit its folding activity. However, Hsp60’s role in AD remains controversial and there is a need for more investigations to understand its role [ 130 ].

The chemical structures of different chaperone molecules: Mizoribine 16 , EC3016 17 , Avrainvillamide 18 , Epolaztaene 19 , MKT-077 20 , YM-01 21 , JG-98 22 , Radicicol 23 , Geldanamycin 24 , 17-AAG 25 , Pochoxime C (OS47720) 26 , R55 27 , and OT1001 28 .

Studies have shown that Hsp70 binds to Aβ42 and prevents self-aggregation. Martín-Peña et al. studied two isoforms of Hsp70, cytosolic and extracellular, in Drosophila flies AD models and evaluated their protective role against memory decline that results from Aβ42 aggregation. The animal studies showed that Hsp70 has a dual function: intracellularly and extracellularly, where it protects against Aβ42 neurotoxicity and synaptic loss. In addition to its ability to bind to tau and its hyper-phosphorylated form and prevent its formation, it decreases aggregation and promotes tau binding to microtubules. Hsp70 acts by activating microglia, insulin-degrading enzyme, and tumor growth facto r- β1, which degrades β-amyloids and prevents memory impairments [ 132 , 133 ]. Some studies in AD brain tissue demonstrated an overexpression of Hsp70 levels and a correlation with the presence of activated glia and stressed neurons. Also, it was found that Hsp70 is associated with extracellular deposits in AD. Drug therapies targeting Hsp70, mainly referring to previous anticancer drugs which target and inhibit Hsp70 ATP-binding site, are considered as candidates in AD treatment due to their ability to reduce tau levels in vitro and ex vivo. MKT-077(1-ethyl-2-(( Z )-(( E )-3-ethyl-5-(3-methylbenzo [ d ]thiazol-2(3 H )-ylidene)-4-oxothiazolidin-2-ylidene)methyl)pyridin-1-ium chloride) ( 20 , Figure 5 ), is an anticancer rhodacyanine compound that binds to mortalin, a mitochondrial Hsp70 site, and acts as an anti-proliferative agent, but the use of this compound was stopped due to toxicity side effects and low BBB penetration. On the other hand, YM-01 ( 21 , Figure 5 ), a more potent MKT-077 derivative, was developed with a single replacement of the ethyl group on the pyridinium nitrogen of MKT-077 with a methyl group. JG-98 ( 22 , Figure 5 ) is also an MKT-077 derivative with a 60-fold higher binding affinity to Hsp70 than YM-01 [ 130 , 134 , 135 , 136 ].

Hsp90 is another type of HSP that regulates the tau phosphorylation and dephosphorylation. An inhibition of Hsp90 results in a decrease in phosphorylation of tau due to a reduction in tau kinases, which is thought to be responsible for tau pathogenesis when it is hyperactivated. Hsp90 inhibitors are used for cancer therapy, but recently, they are considered as promising therapy for AD. Radicicol (RDC) ( 23 , Figure 5 ) and geldanamycin (GA) ( 24 , Figure 5 ) are Hsp90 inhibitors. GA is a natural antifungal compound and the first discovered Hsp90 inhibitor. Studies on this inhibitor were stopped due to its toxicity. On the other hand, 17-AAG (17-(Allylamino)-17-demethoxygeldanamycin) ( 25 , Figure 5 ) is a GA derivative with a lower toxicity and better pharmacokinetic profile that showed a good improvement of the cognitive function by inducing other HSPs, like Hsp70, in addition to reducing NFTs in the transgenic mouse model by blocking the tau phosphorylation pathway, indirectly [ 137 , 138 ]. Pochoxime C (OS47720) ( 26 , Figure 5 ) is also a CNS-permeable Hsp90 inhibitor that showed good safety and efficacy profiles when tested in the AD mouse model. Studies revealed that OS47720 acts by strengthening synaptic function via heat shock factor (HSF-1) activation and dependent transcriptional events [ 139 ].

The combined studies demonstrate that targeting HSPs is a promising strategy to develop drugs with a new mechanism of action for reducing pathogenic tau levels and restoring normal tau homeostasis.

• Vacuolar sorting protein 35 (VPS35)

An accumulation of proteins in neurons and glial cells leads to disturbance of cellular protein homeostasis. The endosomal-lysosomal system is responsible for transporting proteins for recycling and degradation. Any malfunction in the system can lead to several diseases, such as Alzheimer’s disease. Retromer is a complex of regulator proteins composed of sorting nexin (SNX1, 2, 5, 6) and vacuolar sorting proteins (VPS 26, 29, 35), which are responsible for transporting cargo molecules from the endosome to the trans -Golgi network. A loss of retromer’s function results in the downregulation of VPS35, which can increase Aβ formation, induce cognitive impairments, and cause synaptic dysfunction, which is reported in AD patients [ 140 , 141 ]. A study on 3xTg mice brains was conducted to evaluate the effect of VPS35 overexpression on memory function. The study showed that a significant reduction of the Aβ peptide and tau neuropathology (soluble, insoluble, and phosphorylated tau) was associated with overexpression of VPS35, in addition to a reduction in neuroinflammation and ameliorating synaptic dysfunction [ 142 ]. Therefore, VPS35 is an important promising therapeutic target for AD treatment. A small pharmacological chaperones molecule called R55 (thiophene-2,5-diylbis(methylene) dicarbamimidothioatedihydrochloride) ( 27 , Figure 5 ), a thiophenethiourea derivative, can enhance retromer stability and function by increasing retromer proteins, shifting AOO from the endosome, and reducing pathogenic processing of APP, which may serve as a promising therapeutic molecule for neurodegenerative diseases [ 143 ].

Studies demonstrated that the accumulation of gangliosides has been associated with misfolding and aggregation of proteins in neurodegenerative diseases. Abnormal levels of mono-sialoganglioside (GM1, GM2, and GM3) have been reported in AD brains. Mutant forms of Aβ, like Dutch mutant APPE693Q, showed susceptibility to pro-aggregation properties of GM2 and GM3, resulting in the formation of Aβ peptides complexes with gangliosides (ganglioside-bound Aβ (GAβ) peptide) and subsequently leading to an acceleration of aggregation and accumulation of Aβ peptides.

β-hexosaminidase (β-hex) is a lysosomal enzyme that acts by catabolizing GM2 ganglioside, and increasing its activity can lead to a reduction of GM2 levels and Aβ aggregation and accumulation. Small molecules like pharmacological chaperones (PC) can selectively bind and stabilize wild-type proteins and restore their normal folding. OT1001 ( 28 , Figure 5 ) is an iminosugar PC that targets β-hex and increases its level in the brain and reduces GAβ pathology. Studies on Dutch APPE693Q transgenic mice showed that OT1001 has good pharmacokinetics, brain penetration ability, and tolerability, with lower side effects. These make the compound a good drug candidate for increasing the β-hex activity [ 144 ].

6.2.3. Natural Extract

For a long time, natural compounds have been used as therapeutic agents for several pathological diseases, and recent studies showed that they possess a neuroprotective effect. In vitro and in vivo studies have proven that natural compounds possess a therapeutic potential for AD, which allowed some of them to enter the clinical trials stages. Nicotine was the first natural compound entered in the clinical trials for AD, then other compounds like vitamins C, E, and D gained more attention and interest due to their protective role against neuroinflammation and oxidative damage. Recently, bryostatin, a macrolide lactone extract from bryozoan Bugula neritina, has been evaluated and showed the ability to induce α-secretase activity, reduce Aβ production, and enhance the learning and memory in an AD mice model [ 145 ]. Other natural compounds used in folk medicine (traditional Chinese medicine (TCM)) demonstrated a great potential in treating AD by acting on several mechanisms, as shown in Table 2 below [ 146 ].

Natural compounds used in folk medicine and their mechanism of actions.

7. Conclusions

Alzheimer’s disease is now considered a world health concern; as a consequence, the National Institute on Aging—Alzheimer’s Association reclassified and updated the 1984 NINCDS-ADRDA criteria for higher specificity, sensitivity, and early identification of patients at risk of developing AD. Several criteria have been proposed for a more accurate diagnosis of AD, including clinical biomarkers, bodily fluids, and imaging studies. Despite that, the treatment of AD remains symptomatic, without alteration in the disease’s prognosis. Inhibitors to cholinesterase enzyme such as galantamine, donepezil, and rivastigmine, and NMDA antagonists such as memantine, improve memory and alertness but do not prevent progression. Several studies have shown that modification in lifestyle habits like diet and exercise can improve brain health and reduce AD without medical intervention and is considered as a first-line intervention for all AD patients. Recently, the research is focusing on targeting the pathological features of AD such as Aβ and p-tau. Future therapies such as disease-modifying treatment can alter the progression of AD by targeting the Aβ pathway, and many drugs have entered the clinical trials, like AN-1792, solanezumab, bapineuzumab, semagacestat, avagacestat, and tarenflurbil, but failed in demonstrating efficacy in the final clinical stages. Other DMTs are still under investigation, such as those targeting Aβ and tau pathologies, such as aducanumab, gantenerumab, crenezumab, tideglusib, lithium, and others. Other promising compounds called chaperones like heat shock proteins and vacuolar sorting protein 35 (VPS35) function by assisting other proteins to function normally and to arrive at their destination in the cell safely, and therefore can be used as a treatment for neurodegenerative diseases. Moreover, the natural extracts used in folk Chinese medicine showed great potential in treating AD by acting on several mechanisms’ pathways. In conclusion, the success of AD treatment depends on its early administration and patient monitoring for disease progression using biomarkers diagnosis. Future therapies that target tau pathology and the use of combination therapy may have a potential to slow the progression of AD pathology. Designing a potent, selective, and effective drug is urgently needed to treat patients with AD and those at risk for developing the disease.

Author Contributions

Literature survey and first draft writing were done by Z.B., and final draft, including the revisions, were accomplished by R.K. All authors have read and agreed to the published version of the manuscript.

This research received no external funding.

Conflicts of Interest

The authors declare no conflict of interest.

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New Thematic Series - AI in Dementia

Alzheimer's Research & Therapy presents a thematic series focusing on the use of artificial intelligence, machine learning and related techniques in dementia research. 

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Can white matter hyperintensities based Fazekas visual assessment scales inform about Alzheimer’s disease pathology in the population?

Authors: Aishwarya Pradeep, Sheelakumari Raghavan, Scott A. Przybelski, Gregory M. Preboske, Christopher G. Schwarz, Val J. Lowe, David S. Knopman, Ronald C. Petersen, Clifford R. Jack Jr, Jonathan Graff-Radford, Petrice M. Cogswell and Prashanthi Vemuri

Quantitative transport mapping of multi-delay arterial spin labeling MRI detects early blood perfusion alterations in Alzheimer’s disease

Authors: Yihao Guo, Liangdong Zhou, Yi Li, Gloria C. Chiang, Tao Liu, Huijuan Chen, Weiyuan Huang, Mony J. de Leon, Yi Wang and Feng Chen

Clinical application of plasma P-tau217 to assess eligibility for amyloid-lowering immunotherapy in memory clinic patients with early Alzheimer’s disease

Authors: Matthew D. Howe, Karysa J. Britton, Hannah E. Joyce, William Menard, Sheina Emrani, Zachary J. Kunicki, Melanie A. Faust, Brittany C. Dawson, Meghan C. Riddle, Edward D. Huey, Shorena Janelidze, Oskar Hansson and Stephen P. Salloway

Macro and micro structural preservation of grey matter integrity after 24 weeks of rTMS in Alzheimer’s disease patients: a pilot study

Authors: Lucia Mencarelli, Mario Torso, Ilaria Borghi, Martina Assogna, Valentina Pezzopane, Sonia Bonnì, Francesco Di Lorenzo, Emiliano Santarnecchi, Federico Giove, Alessandro Martorana, Marco Bozzali, Gerard R. Ridgway, Steven A. Chance and Giacomo Koch

Prescription medication use in the 10 years prior to diagnosis of young onset Alzheimer’s disease: a nationwide nested case-control study

Authors: Line Damsgaard, Janet Janbek, Thomas Munk Laursen, Karsten Vestergaard, Hanne Gottrup, Christina Jensen-Dahm and Gunhild Waldemar

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Stem cell factor and granulocyte colony-stimulating factor reduce β-amyloid deposits in the brains of APP/PS1 transgenic mice

Authors: Bin Li, Maria E Gonzalez-Toledo, Chun-Shu Piao, Allen Gu, Roger E Kelley and Li-Ru Zhao

Cerebral microbleeds: overview and implications in cognitive impairment

Authors: Sergi Martinez-Ramirez, Steven M Greenberg and Anand Viswanathan

BACE1 inhibitor drugs in clinical trials for Alzheimer’s disease

Authors: Robert Vassar

A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody

Authors: Chad J. Swanson, Yong Zhang, Shobha Dhadda, Jinping Wang, June Kaplow, Robert Y. K. Lai, Lars Lannfelt, Heather Bradley, Martin Rabe, Akihiko Koyama, Larisa Reyderman, Donald A. Berry, Scott Berry, Robert Gordon, Lynn D. Kramer and Jeffrey L. Cummings

The Correction to this article has been published in Alzheimer's Research & Therapy 2022 14 :70

Alzheimer’s disease drug-development pipeline: few candidates, frequent failures

Authors: Jeffrey L Cummings, Travis Morstorf and Kate Zhong

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Alzheimer's Research & Therapy is the major forum for translational research into Alzheimer's disease. An international peer-reviewed journal, it publishes open access basic research with a translational focus, as well as clinical trials, research into drug discovery and development, and epidemiologic studies. The journal also provides reviews, viewpoints, commentaries, debates and reports.

Although the primary focus is Alzheimer's disease, the scope encompasses translational research into other neurodegenerative diseases.

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Alzheimer’s Breakthrough: Researchers Discover Novel Way To Potentially Halt Disease Progression

By The Mount Sinai Hospital / Mount Sinai School of Medicine June 1, 2024

Mount Sinai researchers have discovered a potential new method to treat Alzheimer’s by targeting the plexin-B1 protein to improve plaque clearance in the brain, opening avenues for future therapeutic strategies. Credit: SciTechDaily.com

Innovative research from Mount Sinai has also identified new pathways for research.

Researchers at the Icahn School of Medicine at Mount Sinai have achieved a major breakthrough in Alzheimer’s disease research. Their study identifies a promising method that could potentially slow or even stop the progression of the disease. Focusing on the role of reactive astrocytes and the plexin-B1 protein in Alzheimer’s disease, the research offers vital insights into how brain cells communicate. This opens up new avenues for innovative treatment approaches. The findings were published on May 27 in the journal Nature Neuroscience .

This groundbreaking work is centered on the manipulation of the plexin-B1 protein to enhance the brain’s ability to clear amyloid plaques, a hallmark of Alzheimer’s disease. Reactive astrocytes, a type of brain cell that becomes activated in response to injury or disease, were found to play a crucial role in this process. They help control the spacing around amyloid plaques, affecting how other brain cells can access and clear these harmful deposits.

“Our findings offer a promising path for developing new treatments by improving how cells interact with these harmful plaques,” said Roland Friedel, PhD, Associate Professor of Neuroscience, and Neurosurgery, at Icahn Mount Sinai and a senior author of the study. The research was driven by the analysis of complex data comparing healthy individuals to those with Alzheimer’s, aiming to understand the disease’s molecular and cellular foundations.

Icahn Mount Sinai researchers find PLXNB1, a hub gene predicted to drive a gene subnetwork causally linked to human AD, is upregulated in reactive astrocytes surrounding amyloid plaques. Credit: Bin Zhang, PhD, Icahn Mount Sinai

Broad Implications and Validation of Gene Network Models

Hongyan Zou, PhD, Professor of Neurosurgery, and Neuroscience, at Icahn Mount Sinai and one of the study’s lead authors, highlighted the broader implications of their findings: “Our study opens new pathways for Alzheimer’s research, emphasizing the importance of cellular interactions in developing neurodegenerative disease treatments.”

One of the study’s most significant achievements is its validation of multiscale gene network models of Alzheimer’s disease. “This study not only confirms one of the most important predictions from our gene network models but also significantly advances our understanding of Alzheimer’s. It lays a solid foundation for developing novel therapeutics targeting such highly predictive network models,” said Bin Zhang, PhD, Willard T.C. Johnson Research Professor of Neurogenetics at Icahn Mount Sinai and one of the study’s lead authors. By demonstrating the critical role of plexin-B1 in Alzheimer’s disease, the research underscores the potential of targeted therapies to disrupt the disease’s progression.

The research team emphasizes that while their findings mark a significant advance in the fight against Alzheimer’s, more research is needed to translate these discoveries into treatments for human patients.

“Our ultimate goal is to develop treatments that can prevent or slow down Alzheimer’s progression,” Dr. Zhang added, outlining the team’s commitment to further exploring the therapeutic potential of plexin-B1.

Reference: “Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease” by Yong Huang, Minghui Wang, Haofei Ni, Jinglong Zhang, Aiqun Li, Bin Hu, Chrystian Junqueira Alves, Shalaka Wahane, Mitzy Rios de Anda, Lap Ho, Yuhuan Li, Sangjo Kang, Ryan Neff, Ana Kostic, Joseph D. Buxbaum, John F. Crary, Kristen J. Brennand, Bin Zhang, Hongyan Zou and Roland H. Friedel, 27 May 2024, Nature Neuroscience . DOI: 10.1038/s41593-024-01664-w

This study is supported by the NIH National Institute on Aging (NIA) grants U01AG046170 and RF1AG057440 and is part of the NIA-led Accelerating Medicines Partnership – Alzheimer’s Disease (AMP-AD) Target Discovery and Preclinical Validation program. This public-private partnership aims to shorten the time between the discovery of potential drug targets and the development of new drugs for Alzheimer’s disease treatment and prevention.

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Research on Alzheimer’s Disease and Related Dementias

Alzheimer’s disease and related dementias are a series of complex brain disorders that affect millions of Americans and many more people worldwide. These disorders have an enormous impact on individuals and their families, long-term care facilities, health care providers, health care systems and infrastructure, and the communities in which we all live. As the economic, social, and personal costs of these diseases climb, the research community is working to discover solutions that will improve the lives of those with dementia, their caregivers, and their communities.

The federal government’s Alzheimer’s and related dementias research strategy focuses on engaging a cross-disciplinary team of geneticists, epidemiologists, gerontologists, behavioral scientists, disease and structural biologists, pharmacologists, clinical researchers, and others to bring the greatest and most diverse expertise to the field. This includes training new generations of researchers and clinician-scientists and engaging in innovative partnerships with private industry, nonprofit groups, and more to foster collaboration and broaden access to research resources and data.

Critically, the government’s research strategy includes the search to find treatment and prevention strategies, as well as interventions, services, and supports to improve quality of life for those already living with these diseases and their families.

Who Funds Alzheimer’s and Related Dementias Research?

The National Institutes of Health (NIH) is made up of Institutes, Centers, and Offices that conduct and fund research into all aspects of human health. The National Institute on Aging (NIA) leads NIH’s efforts in clinical, behavioral, and social research in Alzheimer’s and related dementias through efforts aimed at finding ways to treat and ultimately prevent the disorder. NIA collaborates closely with the National Institute of Neurological Disorders and Stroke (NINDS), which manages a research portfolio targeting Alzheimer’s-related dementias. While some of this research takes place in NIH laboratories, the vast majority of NIH support is provided through a competitive grants process to institutions and small businesses across the country. Other federal agencies support a range of activities focused on public health and community programs.

Advances in Alzheimer's and Related Dementias Research

As the nation’s biomedical research agency, NIH supports research ranging from basic biology to drug development and from clinical studies to evaluating public health outcomes. Within the past several decades, researchers have made great strides toward better understanding what causes Alzheimer’s and related dementias and discovering approaches that may prevent, diagnose, and treat them. Some highlights of these efforts include:

• Drug discovery and drug repurposing. Thanks to the substantial investment in Alzheimer’s and related dementias research over the past decade, NIH has increased drug discovery significantly. Of the many compounds in NIH-supported drug development programs for Alzheimer’s and related dementias, 18 new dementia drug candidates have now matured through the pipeline, from discovery in the lab all the way through preclinical development, to reach the stage of human testing. NIA currently supports more than 60 clinical trials testing drug candidates that target many different aspects of the disease. Several of these drug candidates are intended to stop or slow the disease process rather than only treat symptoms. For example, some target amyloid plaques and tau tangles in new ways. Researchers are also exploring multiple ways to repurpose drugs for the potential treatment of dementia, including FDA-approved drugs used to treat epilepsy and diabetes.
• Early detection and diagnosis. Researchers have made significant progress in developing, testing, and validating biomarkers that detect signs of the disease process. For example, in addition to PET scans that detect abnormal beta-amyloid plaques and tau tangles in the brain, NIH-supported scientists have developed the first commercial blood test for Alzheimer’s. This test and others in development can not only help support diagnosis but also be used to screen volunteers for research studies. Other discoveries are leading to the development of potential biomarkers for other dementias. These include the detection of abnormal TDP-43 protein, found in frontotemporal dementias, and a cerebrospinal fluid test to help diagnose Lewy body dementia and Parkinson’s disease. Researchers are also studying behavioral and social indicators, including problems with paying bills and a combined decline in memory and walking speed, that may be early signs of these diseases. Other early markers are also under study.
• Risks factors, genetics, and disease pathways. NIH’s research investments to identify the biological mechanisms that lead to Alzheimer’s and related dementias are fundamental for the discovery of potential drugs that target them. There are many biological pathways that scientists can target with investigational drugs. For example, several recent studies have further revealed how components of the immune system, brain inflammation, vascular disease, and possibly viruses and bacteria — including the many tiny organisms that live in the digestive system, known as the gut microbiome — contribute to the development of these diseases. Scientists are also exploring genetic variations that may contribute to or prevent disease. Recent research has revealed that the genetic risk for Alzheimer’s differs between ethnic and racial groups, highlighting the need for more diversity in genetic research studies. Scientists are also discovering genetic variants that may help protect against Alzheimer’s. Other studies are identifying the genetic underpinnings of related dementias, including new gene variants linked to the development of Lewy body dementia.
• Population studies and precision medicine. By studying large, diverse groups of people, researchers are identifying which genes, behaviors, and lifestyle choices are linked with dementia. Population studies have shown that sedentary behavior, low socioeconomic status, low level of education, and living in a poor neighborhood may increase the risk of developing dementia. These observational discoveries, along with knowledge of genetic and other factors, can be used to advance the development of methods for diagnosis, prevention, and treatment at an individualized level.
• Health disparities and dementia risk. NIH-funded researchers are examining the biological, social, and environmental factors that contribute to the higher prevalence of dementia in Hispanic Americans and Black Americans compared with other White Americans. Since dementia is also underdiagnosed in these populations, researchers are studying approaches to improve diagnoses in underserved communities. NIH is also investing in strategies to increase diversity in research study participants.
• Lifestyle interventions. Researchers are investigating interventions around exercise, healthy eating, cognitive training, preventive health care, and management of chronic conditions, such as high blood pressure, that — if made early in life — may be able to prevent or delay disease symptoms. Emerging areas of study include interventions to enhance cognitive reserve — the mind’s ability to cope with the effects of aging — and interventions to potentially compensate for premature cognitive decline and dementia linked to adverse exposures in early life, such as abuse and malnutrition. NIA currently supports more than 150 trials testing behavioral and lifestyle interventions.
• Dementia care and caregiver support. NIH has significantly expanded research on how to improve dementia care and support for care partners. Researchers are investigating new dementia care models and strategies to equip family caregivers with tools and knowledge to manage the challenges of caring for a loved one with dementia. Studies are also underway to examine ways to improve quality of life for people with dementia and their caregivers. Other studies aim to understand the costs and challenges of dementia, including lost wages and paying for long-term care. NIA currently supports more than 200 studies on dementia care and caregiving.
• Infrastructure development. NIH is continually investing in research infrastructure to advance Alzheimer’s and related dementias research. Efforts in this area include launching a consortium for Alzheimer’s clinical trials, a collaboratory to test interventions to improve care of people with dementia in real-world settings, research efforts to validate cognitive tests in a primary care setting, and centralized data-sharing platforms and other technologies.

Challenges for the Alzheimer’s Research Community

Even with the progress that we’ve made, there’s still a lot of work to do before we can find treatment and prevention strategies for the millions of people affected by Alzheimer’s and related dementias. These devastating diseases are highly complex conditions caused by an interplay of genetic, lifestyle, and environmental factors. They usually develop gradually — changes in the brain take place over years and even decades, long before the first symptoms appear. This complexity presents challenges to the discovery and development of new drugs and other prevention and treatment approaches.

Researchers believe Alzheimer’s and related dementias will likely require multiple treatments customized to individuals. We also know that as the older population continues to grow — aging remains the most important risk factor for dementia — we will see increased numbers of people living with these diseases. That’s why thousands of researchers around the country are working on this issue.

Setting the Federal Research Agenda

NIH takes a collaborative, methodical approach to reviewing progress, identifying gaps, and setting the future agenda for research into Alzheimer’s and related dementias. NIH funding in this area is guided by gaps and opportunities identified in research summits , which alternate yearly to focus on Alzheimer’s, Alzheimer’s-related dementias, or dementia care and services. Smaller, focused workshops are held more frequently on specific aspects of this research.

NIH outlines its Alzheimer’s research efforts in the NIH AD/ADRD Research Implementation Milestones , a research framework detailing specific steps and success criteria toward achieving the goals of the National Plan to Address Alzheimer’s Disease . The milestones also showcase funding initiatives, accomplishments, and highlights of progress toward accomplishing the National Plan goals.

NIH’s research progress is highlighted in the annual Alzheimer’s and related dementias professional judgment budget , which is submitted to Congress each year.

What Is a Professional Judgment Budget?

Each year NIH submits a professional judgment budget that estimates the additional funding needed to advance NIH-supported research into the treatment and prevention of Alzheimer’s and related dementias. The report also summarizes progress and promising research opportunities. Only two other areas of biomedical research — cancer and HIV/AIDS — follow a similar process designed to accelerate research discovery. This approach is often referred to as a “bypass budget” because of its direct transmission to the President and then to Congress without modification through the traditional federal budget process.

Clinical Research Into Alzheimer’s and Related Dementias

No major advance in Alzheimer’s and related dementias treatment, prevention, or care will be possible without robust clinical research. Clinical research includes studies that involve people so scientists can learn more about disease progression, how behavior and lifestyle factors may affect health, and the safety and effectiveness of an intervention. Advances made through clinical research rely on the volunteers who participate in these types of studies. NIA is working on multiple initiatives to enhance recruitment and retention of diverse populations in clinical research. View some of those resources below.

NIA-funded clinical research includes both observational studies through which researchers gather important information, and clinical trials in which researchers test interventions to treat or prevent disease, improve care and caregiver support, and enhance quality of life for people living with dementia. NIA is currently funding more than 400 active clinical trials .

NIA also funds more than 30 Alzheimer’s Disease Research Centers across the country. Scientists at these centers conduct clinical research to improve diagnosis and care for people with dementia and their families, and to find a treatment or increase prevention.

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Find More Resources on Alzheimer’s Research

Explore the resources on this website and linked below to find more information from federal government agencies.

View professional judgment budgets for Alzheimer’s and related dementias from NIH, including yearly updates on research progress.

Browse this database to learn more about research implementation plans and progress toward the goal of treating or preventing Alzheimer’s and related dementias.

Search this repository of resources to support the recruitment and retention of participants into clinical trials and studies on Alzheimer’s disease and related dementias.

Learn about the data sharing policies, considerations, resources, and guidance available to support researchers in safely and efficiently sharing data from their studies.

Visit IADRP to search a database of categorized research across public and private sources.

Learn about NIA's efforts toward the National Plan and NIH annual summits that shape research priorities.

View a list of all active NIA-funded clinical trials, including drug trials, intervention studies, and care and caregiver interventions.

Search for NIA-supported clinical research tools, datasets, samples, visualization tools, and more for Alzheimer’s and related dementias research.

Read the National Strategy for Recruitment and Participation in Alzheimer’s and Related Dementias Research and get resources to support study recruitment.

Read about the National Institute of Neurological Disorders and Stroke’s research into Alzheimer’s disease-related dementias.

Search NIH-funded research in Alzheimer’s and related dementias.

Other Articles in This Section

• Federal Response
• National Research Centers

Questions? Contact the ADEAR Center

The Alzheimer’s & related Dementias Education & Referral (ADEAR) Center is a service of the National Institute on Aging at the National Institutes of Health. Call 800-438-4380 or email [email protected] to talk with an information specialist.

Last updated: July 9, 2024

This content is provided by the National Institute on Aging (NIA), part of the National Institutes of Health. NIA scientists and other experts review this content to ensure it is accurate and up to date.

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Due to the downward trend in respiratory viruses in Maryland, masking is no longer required but remains strongly recommended in Johns Hopkins Medicine clinical locations in Maryland. Read more .

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Research aims to uncover the mysteries of alzheimer’s disease.

Physicians often detect early warning signs of dementia in their aging patients from the stories shared by a patient’s family members. They learn about situations that are out of character, such as paying a bill multiple times, misplacing keys and repeating stories. Often a patient has become more irritable and anxious.

When the clinical examination also suggests that a longtime patient’s behavior or disposition has changed, the next step is to rule out possible causes such as medication issues, poor sleep or traumatic life events, according to Esther Oh , co-director of the Johns Hopkins Memory and Alzheimer’s Treatment Center.

“When there’s clearly some functional impairment going on, I try to figure out why,” she says. “How older patients experience cognitive problems is complex.”

If physicians suspect a patient may have mild cognitive impairment due to Alzheimer’s disease or a related brain disease, they can order a variety of labs including blood tests, MRIs and CT scans, and may refer the patient to Oh and her colleagues in psychiatry, geriatrics or neurology at the Memory and Alzheimer’s Treatment Center.

There, patients can receive individualized treatment based on their needs, including medications targeting memory and cognition and treatments for mood, behavioral and sleep changes. Additionally, patients, caregivers and family members can get guidance and support that helps improve their quality of life, plan for the future and manage inevitable crises.

Much is still unknown about the disease. At this time, there’s no cure for Alzheimer’s, no proven way of slowing down its progression and no treatment available to reverse the deterioration that occurs in the brain.

Best practices for managing the disease include physical and social activity, healthy lifestyle and diet, and a well-structured environment. Older adults who engage in these behaviors appear to have less risk of cognitive and functional decline.

While the diagnosis is grim, Johns Hopkins clinicians and researchers are broadening Alzheimer’s and dementia research and expanding treatment options in a number of ways: searching for biological markers (biomarkers) that could predict Alzheimer’s; determining how to target certain proteins that are present in the brains of patients with the disease; defining the different kinds of Alzheimer’s to tailor future treatment and research; developing new drugs; and piloting a home-based care program.

Defining and Refining

Dementia is a general term that refers to memory loss and decline of other cognitive abilities that limit independence in day-to-day function. Alzheimer’s is the most common brain disease that causes dementia among older adults, accounting for 60%–80% of cases. It affects an estimated one in nine people age 65 and older — 6.2 million Americans. This number is projected to grow to 12.7 million by 2050, according to the Alzheimer’s Association.

Almost two-thirds of the cases are in women, and people of color are at a higher risk of developing Alzheimer’s.

Alzheimer’s is a progressive, neurodegenerative disease that occurs when nerve cells in the brain die. It affects memory, thinking and behavior. But, unlike other forms of dementia, it does not affect patients’ motor function until late stages of the disease.

Alzheimer’s experts think individuals may experience different versions of the disease.

“It’s probably not one kind of Alzheimer’s disease, it’s probably many,” says psychiatrist Paul Rosenberg , co-director of the Johns Hopkins Memory and Alzheimer’s Treatment Center. “What we want to do is find the subtypes so we can find better treatments.”

Cancer treatment, for example, is specific to the kind and subtype of cancer. Breast cancer is treated differently from colon cancer, and within breast cancer, different subtypes mean different treatments. This is the direction in which Johns Hopkins researchers hope to move Alzheimer’s treatment.

Rosenberg and his colleagues, including Memory and Alzheimer’s Treatment Center director Kostas Lyketsos , are crunching data in the Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease to do just that. The goal is to find characteristics that can allow physicians to predict which patients will develop Alzheimer’s, as well as determine what clinical data is necessary to differentiate subtypes of the disease.

The Precision Medicine Center’s patient registry includes more than 130,000 medical records that researchers hope can help define clinical subgroups of patients with dementia, determine when symptoms first develop and when diagnoses occur, among other factors. Additionally, center researchers are developing a collection of unique blood biomarkers that could help target future treatments to subgroups of patients.

Other projects include:

• Analyzing hundreds of MRIs from patients with dementia to look for variations in the size of different structures that could indicate subgroups.
• Studying changes in biomarkers over time to try to measure the progression of dementia.
• Using person-specific stem cells — which are made using a person’s own blood — to create different brain cells in the lab with the potential to predict response to specific medications that may have a role in improving cognitive decline.
• Treating brain vascular disease — an important contributor to dementia — by repurposing an existing drug, atorvastatin, which is typically used to lower cholesterol. Researchers are studying the drug’s effect on the brain’s circulatory system using a new MRI technique.

New Drugs in Development

Other Johns Hopkins researchers are testing a drug that has the potential to slow the progression of Alzheimer’s. Marilyn Albert , director of the Johns Hopkins Alzheimer’s Disease Research Center , Michela Gallagher , a professor of neuroscience at the Johns Hopkins University School of Medicine, and Arnold Bakker , director of the Johns Hopkins Psychiatric Neuroimaging Core , hope to receive FDA approval for the drug for patients in the earliest stages of the disease.

The drug targets two proteins: tau, which serves many functions in healthy neurons but can accumulate into tangles in cells, and amyloid, which forms plaques between cells. Gallagher theorized that periods of hyperactivity in the brain, such as seizures, push those proteins around the brain, spreading more tangles and plaques. She identified a compound, levetiracetam, that calms these hyperactive periods and is now approved by the FDA to treat seizures in patients with epilepsy when used with other medications. She and Albert are testing a time-release capsule version of levetiracetam taken at breakfast by patients in early stages of the disease.

The study , sponsored by AgeneBio , involves more than 164 people taking the drug for 78 weeks at 27 research sites across the country. Preliminary results are expected in fall 2022.

In addition to Albert and Gallagher’s drug, referred to as AGB101, there are more than 100 other Alzheimer’s drugs being tested at Johns Hopkins and elsewhere, according to the Alzheimer’s Association.

Universal Screening

As researchers wrestle with how to catch the disease in its early stages, the question of whether to do universal screening for cognitive impairment remains. Such screening is required as part of the Medicare Annual Wellness visit, initiated in 2011 as part of the Affordable Care Act. While primary care providers must perform this screening for Medicare patients, specialists at Johns Hopkins believe this kind of test can be useful in more targeted ways.

“There could be a place for targeted universal screening, but we have to be very careful,” Oh says. “The question remains, what are you going to do with that information?”

In some scenarios, screening may be appropriate, she says. For example, a patient undergoing surgery who has possible cognitive impairment could be screened in order to make sure they understand the procedure as well as post-op instructions. It could help providers manage possible complications, such as delirium after surgery, which occurs more commonly in individuals with dementia.

The Alzheimer’s Association recommends evaluation for people with memory concerns or cognitive complaints as well as for those with non-memory triggers, including personality change, depression, deterioration of chronic disease without explanation, and falls or balance issues. It is also recommended if a family member or loved one reports cognitive impairment.

Like Oh, Paul Rosenberg and Kostas Lyketsos don’t see a role for universal screening as there’s no demonstrated benefit from it.

“Until we have a safe and effective therapy that people can afford, it is just not ethical to do the tests,” Rosenberg says.

Related Reading

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Focus on Alzheimer's Disease and Related Dementias

What is AD/ADRD?

Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD) refers to the most common forms of dementia. Dementia likely affects more than 6 million people in the U.S. and more than 55 million people worldwide . Currently, there are no known treatments to prevent or stop the progression of dementia. The toll on individuals, caregivers and society is enormous and will increase as the population ages unless effective interventions are developed. NINDS collaborates with NIH ’s National Institute on Aging ( NIA ), the lead NIH Institute for Alzheimer’s disease (AD) research and for NIH's response to the National Plan to Address Alzheimer’s Disease , to establish research priorities and fund biomedical research to decrease the burden of dementia on individuals, families, and communities. 

While AD is the most common dementia diagnosis, ADRDs share many cognitive and pathological features with and can be difficult to distinguish from AD. In fact, more often than not, patients with a clinical diagnosis of Alzheimer’s disease have different mixtures of brain pathologies, complicating both the diagnosis, as well as treatment.  A special video testimonial to raise awareness of the disease burden on patients with AD/ADRD and their caregivers titled “Voices of AD/ADRD” was presented at the NINDS ADRD Summit 2022 , and can be viewed here: Voices of AD/ADRD

In the National Plan to Address Alzheimer’s Disease ,  ADRDs include: Frontotemporal degeneration (FTD) Lewy body dementia (LBD) Vascular contributions to cognitive impairment and dementia (VCID) Multiple-Etiology Dementias (MED)

NINDS and NIA continue to partner in AD/ADRD research planning and implementation, and we urge the research community to join in our efforts to accelerate scientific progress toward reducing the enormous burden and cost of dementia.

No RFA is needed to apply!! NINDS special AD/ADRD payline applies to investigator- Initiated research applications to the NIH Parent R01 and the NINDS R21 ( PA-21-219 )   NINDS AD/ADRD Payline Information   

Funding Opportunity Announcements

Currently active , basic disease mechanisms.

Interaction Between Environmental Factors and Lewy Body Dementia (R01 - Clinical Trial Not Allowed) (PAR-24-249) Due dates: October 04, 2024  Contact PO: David Jett

Mechanistic Investigations into ADRD Associated Protein Structures in Biological Settings (R01 - Clinical Trial Not Allowed) (PAR-24-234) Due dates: October 04, 2024   Contact PO : George Umanah

Investigating Distinct and Overlapping Mechanisms in TDP-43 Proteinopathies, including in LATE, FTD, and other ADRDs (R01 - Clinical Trial Not Allowed) (PAR-24-148) Due dates: June 04, 2024 and October 04, 2024 ; Contact PO: Linda McGavern

Mechanistic Investigations into ADRD Multiple Etiology Dementias (R01 - Clinical Trial Not Allowed) (PAR-24-147) Due dates: June 04, 2024 and October 04, 2024 ; Contact PO: Linda McGavern

Mechanisms of Cognitive Fluctuations in ADRD Populations (R01 - Clinical Trial Optional) (RFA-NS-25-014)   Due date: June 24, 2024 ; Contact PO: Debra Babcock

Mechanistic and Hemodynamic Basis of Diffuse White Matter Disease in Vascular Contributions to Cognitive Impairment and Dementia (VCID) (R01 - Clinical Trial Not Allowed) (PAR-24-196)   Due date:  October 04, 2024 ; Contact PO:  Roderick Corriveau

Protective Strategies to Reduce Amyloid Related Imaging Abnormalities (ARIA) after anti-Aβ immunotherapy (R01 - Clinical Trial Not Allowed) (PAR-24-198)   Due date: October 04, 2024 ;   Contact PO: Francesca Bosetti

Neuropathological Interactions Between COVID-19 and ADRD (R01 - Clinical Trial Not Allowed) (PAR-24-203)   Due date:   October 04, 2024 ; Contact PO:   William P. Daley

Clinical Trial Readiness to Understand and Develop Solutions to Social, Ethical, Behavioral Implications and Barriers to Health Equity in ADRD (R01 - Clinical Trial Not Allowed) ( RFA-NS-25-013) Due date: October 04, 2024 ;  Contact POs:   Richard T. Benson, Rebecca Hommer and Carolina Mendoza-Puccini Email:  [email protected]

Safety and Efficacy of Amyloid-Beta Directed Antibody Therapy in Mild Cognitive Impairment and Dementia with Evidence of Lewy Body Dementia and Amyloid-Beta Pathology (U01 - Clinical Trial Required) (RFA-NS-25-010) Due date: January 24, 2025 ;  Contact PO:   Rebecca Hommer

NINDS Alzheimer’s Disease-Related Dementias (ADRD) Advanced Postdoctoral Career Transition Award (K99/R00 Independent Clinical Trial Not Allowed) (PAR-24-213) Due date: NIH Standard due dates ;   Contact PO:  Amber McCartney

NINDS Alzheimer’s Disease-Related Dementias (ADRD) Advanced Postdoctoral Career Transition Award to Promote Diversity (K99/R00 Independent Clinical Trial Not Allowed)   ( PAR-24-212 )   Due date: NIH Standard due dates ;   Contact PO:   Amelie Gubitz, and  Lauren Ullrich Email:  [email protected]

Notice of Special Interest (NOSI): Administrative Supplements to Promote Diversity for NINDS ADRD Awardees  ( NOT-NS-24-071) Expiration date: February 15, 2027 ;  Contact PO: Amber McCartney

Translational

Functional Target Validation for Alzheimer's Disease-Related Dementias (R61/R33 Clinical Trial Not Allowed) (RFA-NS-25-011) Due date:  November 08, 2024 ; Contact PO:  Pascal Laeng

Advancing Research on Alzheimer's Disease (AD) and AD-Related Dementias (ADRD) (Small Business Innovation Research; R43/R44 Clinical Trial Optional) (PAR-22-196) Due date: NIH  Standard due dates ;  Contact PO:   Annette Gilchrist

Advancing Research on Alzheimer's Disease (AD) and AD-Related Dementias (ADRD) (Small Business Technology Transfer; R41/R42 Clinical Trial Optional) (PAR-22-197) Due date: NIH  Standard due dates ;  Contact PO:   Annette Gilchrist

ADRD Models

Development and Validation of Human Cellular Models for Alzheimer's Disease-Related Dementias (ADRD) (R01 - Clinical Trial Not Allowed) (RFA-NS-24-032)   Due dates:   June 20, 2024 and October 21, 2024 ;  Contact POs:   Linda McGavern  and  Frank Shewmaker

Planned Initiatives

We are excited to share with you the research concepts approved by NINDS Council. Please note that this page will be periodically updated with links when funding opportunities are published. These are also announced via our email listserv (to join the NINDS AD/ADRD listserv, please email [email protected] ).

Please note that an approved concept listed below does not necessarily indicate an award mechanism or funding allocation is imminent or will happen. The NOFO is only official when published in the NIH Guide .

Optimization of Genome Editing Therapeutics for ADRDs- This initiative will support early translational research focused on somatic cell genome editing for Alzheimer's Disease Related Dementias (ADRDs). It is expected that these studies will address the feasibility of using genome editing for therapy development for ADRDs. Contact PO: Timothy LaVaute

Integrative Multiomics Profiling for Lewy Body Dementia- This initiative is designed to support research to conduct genetic and molecular characterization of LBD. This may include whole genome sequencing, longitudinal bulk-transcriptomics, longitudinal matched plasma, and cerebrospinal fluid (CSF) proteomic analysis, and post-mortem single-cell RNA sequencing, which will be generated and paired with harmonized longitudinal clinical data. Contact PO: Christine Swanson-Fischer

ADRD Risk and Disease Following Nervous System Exposures at Biological Interfaces with the Environment- This initiative is to support research that aim to by determine how exposures at innervated human surfaces affect ADRD disease mechanisms and phenotypic outcomes. These exposures include toxins and toxic chemicals, viral and other pathogens, and other environmental exposures. Contact PO: David Jett

Including ADRD Biomarker Measures and APOE Genotype Status to ADRD Human Subjects Research Studies- This initiative is to provide funding to existing AD/ADRD cohort studies to support the inclusion/addition of ADRD fluid-based biomarker measures and APOE genotype status when they are not already utilized in the original study. Contact PO: Amber McCartney

IND -enabling Studies and Clinical Trials for Genome Editing Therapeutics for Alzheimer's Disease and Alzheimer's Disease-Related Dementias -  This initiative support Investigational New Drug (IND) enabling studies for the preparation and submission of an IND for a genome editing therapeutics for ADRD, and optional small delayed-onset first in human Phase I clinical trial.  Contact PO:   Timothy LaVaute

Recently Closed Funding Opportunities 

VCID Center Without Walls for Understanding and Leveraging Small Vessel Cerebrovascular Disease Mechanisms in ADRD (R01 - Clinical Trial Not Allowed)  ( RFA-NS-24-027)  

Blood Brain Barrier Response to Antibodies Targeting Beta-Amyloid   (R01 - Clinical Trial Not Allowed)   (PAR-23-140) 

Role of Environmental Stress in the Health Inequities of Alzheimer's Disease-Related Dementias (ADRD)   (R01 -  Clinical Trial  Not Allowed) ( RFA-NS-24-024)  

Mechanistic Investigations into ADRD Multiple Etiology Dementias   (R01 - Clinical Trial Not Allowed)  (PAR-23-211)  

Investigating Distinct and Overlapping Mechanisms in TDP-43 Proteinopathies, including in LATE, FTD, and other ADRDs   (R01 - Clinical Trial Not Allowed)  (PAR-23-212) 

Neuropathological Interactions Between COVID-19 and ADRD   (R01 - Clinical Trial Not Allowed)  (PAR-23-214)  

Efficacy and Safety of Amyloid-Beta Directed Antibody Therapy in Mild Cognitive Impairment and Dementia with Evidence of Both Amyloid-Beta and Vascular Pathology   (U01 - Clinical Trial Required) (RFA-NS-24-013)

Tools and Resources to Understand the Vascular Pathophysiology of in vivo Neuroimaging Findings in ARIA (U24 - Clinical Trials Not Allowed) (RFA-NS-24-034) Using Multimodal Biomarkers to Differentially Diagnose ADRDs for Clinical Trials   (U19 Clinical Trial Optional)   (RFA-NS-24-001)  

Validating digital health technologies for monitoring biomarkers in ADRD clinical trials   (R61/R33 - Clinical Trials Optional) (RFA-NS-24-026)  

Assessment of TBI-related ADRD Pathology Related to Cognitive Impairment and Dementia Outcomes  (U01 - Clinical Trial Not Allowed) (RFA-NS-24-003)  

Administrative Supplements to Promote Diversity for NINDS AD/ADRD Awardees (NOT-NS-21-047)  

NINDS Institutional AD/ADRD Research Training Program (T32 Clinical Trial Not Allowed) ( PAR-23-113)

Simultaneous and Synergistic Multi-Target Validation for Alzheimer’s Disease-Related Dementias  (R61/R33  Clinical Trial  not allowed)   ( PAR-23-195)  

Early-Stage Therapy Development for Alzheimer's Disease-Related Dementias (ADRD)   (R61/R33 - Clinical Trial Not Allowed) ( RFA-NS-24-010)  

Optimization of Genome Editing Therapeutics for Alzheimer's Disease-Related Dementias (ADRD)  (U01 - Clinical Trials Not Allowed) (RFA-NS-24-009)    

Center without Walls for PET Ligand Development for Alzheimer's disease-related dementias (ADRDs)   (U19 - Clinical Trial Optional) ( RFA-NS-19-014) 

Development & Characterization of Experimental models of post-TBI ADRD   (R01 - Clinical Trial Not Allowed)  (PAR-23-218)  

Development and Validation of Models for ADRD   (R61/R33 - Clinical Trial Not Allowed)   (PAR-23-154) 

NINDS Leads ADRD Research Priority-Setting Planning Efforts

NINDS-led ADRD summits represent a continuous decade long planning effort. ADRD summits occur every three years and respond to the National Plan to Address Alzheimer’s Disease (“National Plan”) that was released in 2012 and updated annually. These Summits set national research recommendations with timelines that reflect critical scientific priorities for research on ADRD. During each ADRD Summit planning process, the established prioritized recommendations are updated, and developed further, under the leadership of the ADRD Summit Steering Committee, which includes a Working Group of the NANDS Council. The Committee solicits input from nationally and internationally recognized dementia-science experts, as well as public and private stakeholders. The resulting recommendations guide ADRD research for the next several years. Links to NANDS Council-approved ADRD Summit Reports are provided below.

ADRD Summit 2022 FACA Report; (pdf, 3804 KB)   ADRD Summit 2022 Research Milestones and Success Criteria (pdf, 512 KB)

ADRD Summit 2019 FACA Report (pdf, 2131 KB) ;  ADRD Summit 2019 Research Milestones and Success Criteria

ADRD Summit 2016 FACA Report (pdf, 922 KB) ; ADRD Summit 2016 Research Milestones and Success Criteria ;  Proceedings Article

ADRD Summit 2013 FACA Report (pdf, 980 KB) ;  ADRD Summit 2013 Research Milestones and Success Criteria ;  Proceedings Article   

Rod Corriveau  | Program Director and ADRD Lead  [email protected]  

Sara Dodson  | Senior Health Science Policy Analyst [email protected]

Erin Bryant  |  Office of Neuroscience Communications & Engagement (ONCE) [email protected]

Amber McCartney | Scientific Project Manager [email protected]

Arvind Shukla  | Health Program Specialist [email protected]

Herson Rene Astacio Cuevas  | Health Program Specialist [email protected]  

Kiara Bates  | Program Specialist [email protected]

Related Topics  AD+ADRD Research Implementation Milestones database The AD+ADRD Research Implementation Milestones database   is a research framework detailing specific steps and success criteria towards achieving the goal of the  National Plan to Address Alzheimer's Disease : to treat and prevent AD and ADRDs by 2025. This database includes research milestones and responsive activities for the NIH triennial AD, ADRD, and Dementia Care, Services and Supports research summits. International Alzheimer's and Related Dementias Research Portfolio IADRP reports categories of funded research supported by public and private organizations both in the US and abroad all categorized using the  Common Alzheimer's and Related Dementias Research Ontology (CADRO)

NIH Estimates of Funding for Various Research, Condition, and Disease Categories

*Dollars in millions and rounded To learn more about NIH Investment in AD/ADRD, please visit the Categorical Spending site and enter "Alzheimer's Disease Including Alzheimer's Disease Related Dementias".

Holtzman, Chen recognized for exceptional Alzheimer’s research

Washington University School of Medicine in St. Louis faculty members  David M. Holtzman, MD , the Barbara Burton and Reuben M. Morriss III Distinguished Professor of Neurology, and  Xiaoying Chen , an instructor in neurology, were awarded the inaugural Jeffrey L. Morby Prize from the Cure Alzheimer’s Fund, a nonprofit dedicated to supporting the most promising research to prevent, slow or reverse Alzheimer’s disease.

The prize recognizes the senior and first authors of a recent scientific publication that transforms the fundamental understanding of Alzheimer’s disease and opens new paths to translate scientific results into effective ways to prevent, diagnose or treat the neurodegenerative condition.

Read more on the School of Medicine website .

Comments and respectful dialogue are encouraged, but content will be moderated. Please, no personal attacks, obscenity or profanity, selling of commercial products, or endorsements of political candidates or positions. We reserve the right to remove any inappropriate comments. We also cannot address individual medical concerns or provide medical advice in this forum.

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Diagnosing different forms of dementia now possible using artificial intelligence

Ten million new cases of dementia are diagnosed each year but the presence of different dementia forms and overlapping symptoms can complicate diagnosis and delivery of effective treatments. Now researchers from Boston University have developed an AI tool that can diagnose ten different types of dementia such as vascular dementia, Lewy body dementia, and frontotemporal dementia, even if they co-occur.

The researchers created a multimodal Machine Learning (ML) framework that accurately identifies specific pathologies causing dementia using commonly collected clinical data, such as demographic information, patient- and family-level medical history, medication use, neurological and neuropsychological exam scores and neuroimaging data such as MRI scans.These findings appear online in Nature Medicine .

"Our generative AI tool enables differential dementia diagnosis using routinely collected clinical data, showing its potential as a scalable diagnostic tool for AD and related dementias," says corresponding author Vijaya B. Kolachalama, PhD, FAHA, associate professor of medicine at Boston University Chobanian & Avedisian School of Medicine. "The ability to generate diagnosis with routine clinical data is becoming increasingly important given the significant challenges in accessing gold-standard testing, not only in remote and economically developing regions and in urban healthcare centers," adds Kolachalama who also is an associate professor of computer science, affiliate faculty of Hariri Institute for Computing, and a founding member of the Faculty of Computing & Data Sciences at Boston University.

In the study, the multimodal ML framework was trained on data from more than 50,000 individuals from nine different global datasets. The model achieved an area under the receiver operating characteristic (ROC) curve of 0.96 in differentiating the dementia types. The ROC score can range from 0 to 1. A score of 0.5 indicates random guessing, and a score of 1 indicates perfect performance.

The team also compared the performance of neurologists and neuro-radiologists working alone versus with the AI tool, and found that AI can boost the accuracy of neurologists by more than 26% across all 10 dementia types. Using 100 randomly selected cases, 12 neurologists were asked to make a diagnosis and provide a confidence score between 0 to 100. This confidence score was then averaged with the probability score obtained by the AI tool to obtain an AI-augmented neurologist score.

"There aren't enough neurology experts around the world, and the number of patients needing their help is growing quickly. This mismatch is putting a big strain on the healthcare system. We believe AI can help by identifying these disorders early and assisting doctors in managing their patients more effectively, preventing the diseases from getting worse," says Kolachalama.

With dementia cases set to double in the next 20 years, the researchers hope that this AI tool can provide accurate differential diagnosis and support the increased demand in targeted therapeutic interventions for dementia.

This project was supported by grants from the Karen Toffler Charitable Trust, National Institute on Aging's Artificial Intelligence and Technology Collaboratories (P30-AG073014), the American Heart Association (20SFRN35460031), Gates Ventures, and the National Institutes of Health (R01-HL159620, R21-CA253498, R43-DK134273, RF1-AG062109, U19-AG068753, P20-GM130447, K23-NS075097, P50-AG047366, and R01-NS115114)

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Story Source:

Materials provided by Boston University School of Medicine . Note: Content may be edited for style and length.

Journal Reference :

• Chonghua Xue, Sahana S. Kowshik, Diala Lteif, Shreyas Puducheri, Varuna H. Jasodanand, Olivia T. Zhou, Anika S. Walia, Osman B. Guney, J. Diana Zhang, Serena T. Pham, Artem Kaliaev, V. Carlota Andreu-Arasa, Brigid C. Dwyer, Chad W. Farris, Honglin Hao, Sachin Kedar, Asim Z. Mian, Daniel L. Murman, Sarah A. O’Shea, Aaron B. Paul, Saurabh Rohatgi, Marie-Helene Saint-Hilaire, Emmett A. Sartor, Bindu N. Setty, Juan E. Small, Arun Swaminathan, Olga Taraschenko, Jing Yuan, Yan Zhou, Shuhan Zhu, Cody Karjadi, Ting Fang Alvin Ang, Sarah A. Bargal, Bryan A. Plummer, Kathleen L. Poston, Meysam Ahangaran, Rhoda Au, Vijaya B. Kolachalama. AI-based differential diagnosis of dementia etiologies on multimodal data . Nature Medicine , 2024; DOI: 10.1038/s41591-024-03118-z

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Artificial intelligence outperforms clinical tests at predicting progress of Alzheimer’s disease

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Cambridge scientists have developed an artificially-intelligent tool capable of predicting in four cases out of five whether people with early signs of dementia will remain stable or develop Alzheimer’s disease.

We’ve created a tool which is much more sensitive than current approaches at predicting whether someone will progress from mild symptoms to Alzheimer’s Zoe Kourtzi

The team say this new approach could reduce the need for invasive and costly diagnostic tests while improving treatment outcomes early when interventions such as lifestyle changes or new medicines may have a chance to work best.

Dementia poses a significant global healthcare challenge, affecting over 55 million people worldwide at an estimated annual cost of $820 billion. The number of cases is expected to almost treble over the next 50 years.

The main cause of dementia is Alzheimer’s disease, which accounts for 60-80% of cases. Early detection is crucial as this is when treatments are likely to be most effective, yet early dementia diagnosis and prognosis may not be accurate without the use of invasive or expensive tests such as positron emission tomography (PET) scans or lumbar puncture, which are not available in all memory clinics. As a result, up to a third of patients may be misdiagnosed and others diagnosed too late for treatment to be effective.

A team led by scientists from the Department of Psychology at the University of Cambridge has developed a machine learning model able to predict whether and how fast an individual with mild memory and thinking problems will progress to developing Alzheimer’s disease. In research published today in eClinical Medicine , they show that it is more accurate than current clinical diagnostic tools.

To build their model, the researchers used routinely-collected, non-invasive, and low-cost patient data – cognitive tests and structural MRI scans showing grey matter atrophy – from over 400 individuals who were part of a research cohort in the USA.

They then tested the model using real-world patient data from a further 600 participants from the US cohort and – importantly – longitudinal data from 900 people from memory clinics in the UK and Singapore.

The algorithm was able to distinguish between people with stable mild cognitive impairment and those who progressed to Alzheimer’s disease within a three-year period. It was able to correctly identify individuals who went on to develop Alzheimer’s in 82% of cases and correctly identify those who didn’t in 81% of cases from cognitive tests and an MRI scan alone.

The algorithm was around three times more accurate at predicting the progression to Alzheimer’s than the current standard of care; that is, standard clinical markers (such as grey matter atrophy or cognitive scores) or clinical diagnosis. This shows that the model could significantly reduce misdiagnosis.

The model also allowed the researchers to stratify people with Alzheimer’s disease using data from each person’s first visit at the memory clinic into three groups: those whose symptoms would remain stable (around 50% of participants), those who would progress to Alzheimer’s slowly (around 35%) and those who would progress more rapidly (the remaining 15%). These predictions were validated when looking at follow-up data over 6 years. This is important as it could help identify those people at an early enough stage that they may benefit from new treatments, while also identifying those people who need close monitoring as their condition is likely to deteriorate rapidly.

Importantly, those 50% of people who have symptoms such as memory loss but remain stable, would be better directed to a different clinical pathway as their symptoms may be due to other causes rather than dementia, such as anxiety or depression.

Senior author Professor Zoe Kourtzi from the Department of Psychology at the University of Cambridge said: “We’ve created a tool which, despite using only data from cognitive tests and MRI scans, is much more sensitive than current approaches at predicting whether someone will progress from mild symptoms to Alzheimer’s – and if so, whether this progress will be fast or slow.

“This has the potential to significantly improve patient wellbeing, showing us which people need closest care, while removing the anxiety for those patients we predict will remain stable. At a time of intense pressure on healthcare resources, this will also help remove the need for unnecessary invasive and costly diagnostic tests.”

While the researchers tested the algorithm on data from a research cohort, it was validated using independent data that included almost 900 individuals who attended memory clinics in the UK and Singapore. In the UK, patients were recruited through the Quantiative MRI in NHS Memory Clinics Study (QMIN-MC) led by study co-author Dr Timothy Rittman at Cambridge University Hospitals NHS Trust and Cambridgeshire and Peterborough NHS Foundation Trusts (CPFT).

The researchers say this shows it should be applicable in a real-world patient, clinical setting.

Dr Ben Underwood, Honorary Consultant Psychiatrist at CPFT and assistant professor at the Department of Psychiatry, University of Cambridge, said: “Memory problems are common as we get older. In clinic I see how uncertainty about whether these might be the first signs of dementia can cause a lot of worry for people and their families, as well as being frustrating for doctors who would much prefer to give definitive answers. The fact that we might be able to reduce this uncertainty with information we already have is exciting and is likely to become even more important as new treatments emerge.”

Professor Kourtzi said: “AI models are only as good as the data they are trained on. To make sure ours has the potential to be adopted in a healthcare setting, we trained and tested it on routinely-collected data not just from research cohorts, but from patients in actual memory clinics. This shows it will be generalisable to a real-world setting.”

The team now hope to extend their model to other forms of dementia, such as vascular dementia and frontotemporal dementia, and using different types of data, such as markers from blood tests.

Professor Kourtzi added: “If we’re going to tackle the growing health challenge presented by dementia, we will need better tools for identifying and intervening at the earliest possible stage. Our vision is to scale up our AI tool to help clinicians assign the right person at the right time to the right diagnostic and treatment pathway. Our tool can help match the right patients to clinical trials, accelerating new drug discovery for disease modifying treatments.”

This work was in collaboration with a cross-disciplinary team including Professor Peter Tino at the University of Birmingham and Professor Christopher Chen at the National University of Singapore. It was funded by Wellcome, the Royal Society, Alzheimer’s Research UK, the Alzheimer’s Drug Discovery Foundation Diagnostics Accelerator, the Alan Turing Institute, and the National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Reference Lee, LY & Vaghari, D et al. Robust and interpretable AI-guided marker for early dementia prediction in real-world clinical settings. eClinMed; 12 July 2024; DOI: 10.1016/j.eclinm.2024.102725

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Racial disparities in dementia determined by social factors rather than genetic ancestry, finds study

by Washington University School of Medicine

Racial disparities in dementia are due to social determinants of health, with genetic ancestry playing no role, according to a new study led by researchers at Washington University School of Medicine in St. Louis.

The study, which was based on a long-running population-based survey in four Latin American countries, helps explain why people of predominantly Native American or African ancestry have a higher prevalence of dementia : Study participants were more likely to experience social contexts and health conditions that raised their risk of cognitive decline , such as lower education levels, rural residency and high blood pressure . Once such factors were accounted for, ancestry added no additional risk.

"Marginalized racial and ethnic groups have higher rates of dementia in many countries, and disentangling the biological from the social contributors has been challenging," said corresponding author Jorge Llibre-Guerra, MD, an assistant professor of neurology.

"Latin America provides a unique framework to separate the two. It is the region with the largest mixture of genetic ancestries, plus it has profound social inequalities. This study clearly shows that poor cognitive health is part of the legacy of the racial caste system. It's not family ancestry that is putting people at risk. In a way, the findings are reassuring, because social determinants of health are modifiable."

The study is published in the journal Alzheimer's & Dementia .

Once thought to be a natural and inevitable part of aging, cognitive decline and dementia increasingly have been recognized as products of a complex web of risk factors more likely to ensnare members of marginalized groups. In the U.S., for example, dementia is about twice as common in Black communities and 1½ times as common in Hispanic communities, compared with white populations.

What remains unclear is how much of the increased rate of dementia is due to modifiable risk factors linked to marginalization, such as education level and high blood pressure, and how much is due to genetic susceptibility associated with ancestry.

The first step in disentangling the roles of biological and social factors is to replace the complicated issue of racial and ethnic identity with the simpler matter of genetic ancestry. Race and ethnicity are not biological categories; they are defined by the cultures and societies in which people live, and the definitions vary by time and place. Genetic ancestry, on the other hand, is an objective measure of the proportion of an individual's DNA that can be traced back to one or more large areas of the globe—in this case, Africa, Europe or the Americas.

Llibre-Guerra and colleagues analyzed the relationship between genetic ancestry, social determinants of health, and cognitive function using survey data obtained by the 10/66 Dementia Research Group in Cuba, the Dominican Republic, Mexico and Peru.

The 10/66 group was established in 1998 to study the prevalence and impact of dementia in low- and middle-income countries by using population-based surveys that are internationally validated and standardized. The current study utilized data from the 10/66 group's first survey wave, conducted from 2004 to 2006. The first wave marks the beginning of systematic data collection across diverse settings and provides a critical benchmark for all subsequent analyses. The 10/66 group has since conducted two follow-up surveys and plans to continue expanding these assessments moving forward.

Eligible participants were found by trained surveyors who knocked on all doors in designated areas, a strategy designed to generate representative samples for each country. Each participant underwent an interview, physical examination, cognitive assessment and blood draw. In addition, surveyors interviewed a close relative or friend of each participant.

For the current study, the researchers analyzed deidentified data on 3,808 people ages 65 or older across the four countries. Individuals were categorized as predominantly of African, Native American or European ancestry if 70% or more of their DNA could be traced to the respective continent.

Each country had a unique mixture of ancestries. In Mexico and Peru, the greatest number of people were primarily of Native American heritage, followed by European and then African. In Cuba, most were of European ancestry, followed by African, with less than 3% Native American. In the Dominican Republic, most people were of African heritage, followed by European, with about 10% of Native American heritage.

The survey revealed that cognitive impairment was more common among older people of Native American or African ancestry than of European ancestry. While 47.8% of seniors of European heritage exhibited some degree of cognitive impairment, 52.7% of those with Native American ancestry and 54.9% of those with African ancestry showed such impairments. Once social and health factors such as education level, socio-economic status and cardiovascular health were taken into account, the association between genetic ancestry and cognitive performance disappeared.

"Our findings suggest that cognitive performance is largely influenced by upstream societal risk factors," the authors wrote in the study. "We found substantial disparities in social determinants of health among different ancestry groups in Latin America, stemming from enduring disadvantages and structural racism rooted in the colonial period."

The study findings echo what has been observed in the U.S., with marginalized groups experiencing higher rates of dementia and similar social inequities such as lower education attainment and reduced access to health care. "If we want to improve cognitive health for all people," Llibre-Guerra said, "we need to start by addressing these factors."

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FDA approves treatment for adults with Alzheimer’s disease

Originally posted in FDA Press Announcements

The U.S. Food and Drug Administration has approved Kisunla (donanemab-azbt) injection for the treatment of Alzheimer’s disease. Treatment with Kisunla should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in the clinical trials.

Kisunla is administered as an intravenous infusion every four weeks. The recommended dosage is detailed in the prescribing information .

Disease or Condition

Alzheimer’s disease  is an irreversible, progressive brain disorder affecting more than 6.5 million Americans that slowly destroys memory and thinking skills and, eventually, the ability to carry out simple tasks. While the specific causes of Alzheimer’s are not fully known, it is characterized by changes in the brain—including amyloid beta plaques and neurofibrillary, or tau, tangles—that result in loss of neurons and their connections. These changes affect a person’s ability to remember, think and speak.

Effectiveness 

The efficacy of Kisunla was evaluated in a double-blind, placebo-controlled, parallel-group study (Study 1, NCT04437511) in patients with Alzheimer’s disease. The patients had confirmed presence of amyloid pathology and mild cognitive impairment or mild dementia stage of disease. 1736 patients were randomized 1:1 to receive 700 mg Kisunla every 4 weeks for the first 3 doses, and then 1400 mg every 4 weeks (N = 860) or placebo (N = 876) for a total of up to 72 weeks. The treatment was switched to placebo based on a prespecified reduction in amyloid levels measured by positron emission tomography (PET) at Week 24, Week 52, and Week 76.

Patients treated with Kisunla demonstrated a statistically significant reduction in clinical decline on the Integrated Alzheimer's Disease Rating Scale (iADRS) compared to placebo at Week 76 in the overall population (2.92, p<0.0001), as well as on the iADRS component scales, the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog13) (-1.33, p=0.0006) and the Alzheimer’s Disease Cooperative Study – instrumental Activities of Daily Living (ADCS-iADL) scale (1.70, p=0.0001). Patients treated with Kisunla also demonstrated a statistically significant reduction in clinical decline on the Clinical Dementia Rating Scale – Sum of Boxes (CDR-SB) compared to placebo at Week 76 in the overall population (-0.70, p<0.0001).

At baseline, the study population had a mean age of 73 years, with a range of 59 to 86 years. Fifty-seven percent of patients were female, 91% were White, 6% were Asian, 4% were Hispanic or Latino, and 2% were Black or African American.

Safety Information

The prescribing information includes a boxed warning for amyloid-related imaging abnormalities (ARIA). ARIA most commonly presents as temporary swelling in areas of the brain that usually resolves over time and may be accompanied by small spots of bleeding in or on the surface of the brain. ARIA usually does not have symptoms, although serious and life-threatening events rarely can occur.

Patients who are APOE ε4 homozygotes have a higher incidence of ARIA, including symptomatic and serious ARIA, compared to heterozygotes and noncarriers. Testing for APOE ε4 status should be performed prior to beginning treatment to inform the risk of developing ARIA.

There is risk of infusion-related reactions, with symptoms such as flu-like symptoms, nausea, vomiting and changes in blood pressure, and hypersensitivity reactions, including anaphylaxis (severe, life-threatening allergic reaction) and angioedema (swelling).

The most common side effects of Kisunla were ARIA and headache.

See full prescribing information  (PDF, 664K) for additional information on risks associated with Kisunla.

Designations

The FDA granted this application Fast Track , Priority Review , and Breakthrough Therapy designations.

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FDA Approves New Drug to Treat Alzheimer's

TUESDAY, July 2, 2024 (HealthDay News) -- A new drug to treat Alzheimer's disease was approved by the U.S. Food and Drug Administration on Tuesday.

In clinical trials, donanemab (Kisunla) modestly slowed the pace of thinking declines among patients in the early stages of the memory-robbing disease. But it also carried significant safety risks, including swelling and bleeding in the brain.

"Kisunla demonstrated very meaningful results for people with early symptomatic Alzheimer's disease, who urgently need effective treatment options. We know these medicines have the greatest potential benefit when people are treated earlier in their disease, and we are working hard in partnership with others to improve detection and diagnosis,"  Anne White , executive vice president and president of Lilly Neuroscience, said in a company news release announcing the approval. "Each year, more and more people are at risk for this disease, and we are determined to make life better for them."

Alzheimer's advocates applauded the approval.

"This approval marks another step forward in evolving the standard of care for people living with Alzheimer's disease that will ultimately include an arsenal of novel treatments, providing much needed hope to the Alzheimer's community," Dr. Howard Fillit , co-founder and chief science officer at the Alzheimer's Drug Discovery Foundation, said in the Lilly news release. "Diagnosing and treating Alzheimer's sooner than we do today has the potential to meaningfully slow disease progression, giving patients invaluable time to maintain their independence for longer."

Kisunla is similar to another drug, Leqembi, approved to treat Alzheimer's last year. Both attack amyloid protein, which is involved in the development of Alzheimer’s, and both slowed dementia by several months. Leqembi is given every two weeks, while Kisunla is given monthly as an intravenous infusion.

Kisunla has another significant difference that will likely appeal to patients and doctors alike: The drug can be stopped once it clears all of the amyloid plaques from the brain.

“Once you’ve removed the target that you’re going after, you then can stop dosing,” said White, adding that this could cut the cost and inconvenience of the treatment as well as the risk of side effects.

In the company's trial, 17 percent of patients receiving donanemab were able to discontinue the drug at six months; 47 percent stopped within a year; and 69 percent stopped within 18 months. Importantly, their cognitive decline continued to slow even after they stopped.

Still, the treatment won't come cheap: The list price for Kisunla will be $32,000 a year. Leqembi costs $26,000 per year, but it is continued after all amyloid is cleared.

About one-fourth of those on donanemab experienced swelling or bleeding in the brain. While most of the cases were mild, roughly 2% were serious, and the side effects were linked to three patients' deaths.

With both drugs, patients at higher risk include those who have had more than four microscopic bleeds in the brain and those with an Alzheimer’s-linked gene variant called APOE4 — especially if they have two copies of the variant, the Times reported.

Some experts worry that emphasis on anti-amyloid drugs might discourage patients from participating in trials for treatments that could be better.

“For the field generally, I think this is moving sideways, and it’s slowing progress,” Dr. Michael Greicius , a neurologist at Stanford University School of Medicine, told the Times.

Dozens of other drugs are in clinical trials for Alzheimer’s, including drugs attacking important features like tau tangles and neuroinflammation, the Times reported.

More information

The Alzheimer's Association has more on Alzheimer's drugs .

SOURCES: U.S. Food and Drug Administration, news release, July 8, 2024; New York Times

What This Means For You

Patients with Alzheimer's disease now have a new way to treat it. Kisunla is now approved by the U.S. Food and Drug Administration.

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TUESDAY, July 2, 2024 (HealthDay News) -- A new drug to treat Alzheimer's disease was approved by the U.S. Food and Drug Administration on Tuesday.. In clinical trials, donanemab (Kisunla) modestly slowed the pace of thinking declines among patients in the early stages of the memory-robbing disease.

Class 9 Pak Studies Chapter 3 Exercise MCQs Test

Federal Board,  FBISE  Class 9 Pak Studies Chapter 3 MCQs Test is available on this page. Chapter-wise MCQs Tests of Pak Studies are also available on our website.

Class 9 Pak Studies Chapter 3 Exercise Practice MCQs Test

1. The ______ mountain range makes the boundary line between Pakistan and Afghanistan.

2. The Muslim Bagh and Ziarat hills are situated in the _______ plateau.

3. At one point near Sakesar, the Salt range rises to the height of ______ meter from the sea level.

4. Only ______ percent of the Pakistan area is covered with forests.

5. The border line between Pakistan and China is ______ km long.

6. K2 is the _____ highest mountain in the world.

7. Sibbi and _______ are among the hottest places on the earth.

8. The coastal line of Pakistan is ______ km long.

9. The national bird of Pakistan is _______.

10. The total area of Pakistan is _________ Square km.

11. Murree and Hazara Hills are part of the _______ Mountain range.

12. The only continent in the world so far immunes from deforestation is _______.

13. The THAL desert is situated in the _________ province of Pakistan.

14. Durand Line is _________ km long.

15. The river Indus originates from lake _______.

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As Misery Multiplies, Pakistanis Rise Up Against the Ruling Elite

Unrest over a range of economic and security issues threatens to deepen the political turmoil that has plagued Pakistan for years.

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By Christina Goldbaum and Salman Masood

Christina Goldbaum reported from London, and Salman Masood from Islamabad, Pakistan.

In almost every corner of Pakistan, anger at the ruling elite is nearing a boiling point.

Thousands have protested soaring electricity bills just outside the capital, Islamabad. In a major port city in the southwest, dozens have clashed with security officers over what they described as forced disappearances of activists. In the northwest, protesters have admonished the country’s generals for a recent surge in terrorist attacks.

The demonstrations over the past few weeks reflect frustration with Pakistan’s shaky, five-month-old government and with its military, the country’s ultimate authority. The unrest threatens to plunge Pakistan back into the depths of political turmoil that has flared in recent years and that many had hoped would subside after the February general election.

Pakistan’s leaders are confronted with a monsoon of problems. The economy is suffering its worst crisis in decades . Anger at an election widely viewed as manipulated by the military remains palpable. Militant violence has roared back after the Taliban’s return to power in neighboring Afghanistan. And Pakistani politics are more polarized than ever, with the country’s most popular political figure sitting in jail after a bitter rift with the military.

The administration of the current prime minister, Shehbaz Sharif, has struggled to establish its legitimacy and has been criticized as little more than a front for the military.

Since Mr. Sharif first came into office in 2022, Pakistan’s generals have wielded an increasingly heavy hand to quash dissent. A national firewall has been installed to censor internet content, the social media platform X has been blocked, security forces have arrested political opponents in droves, and generals have been installed in key positions in the civilian government.

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Kurram clashes: How a Pakistani land dispute led to a deadly tribal battle

At least 46 people were killed and 200 injured in clashes until a temporary ceasefire was agreed upon on Wednesday.

Islamabad, Pakistan – After weeklong clashes between rival tribes in Pakistan’s district of Kurram, killing at least 46 people and injuring nearly 200, fighting has now halted, following a meeting between authorities and tribal elders.

A grand jirga, or a gathering of tribal elders, along with civilian and security officials, met in Parachinar, the main city in Kurram district. They held an hours-long meeting on Wednesday, after which a ceasefire was agreed upon by all stakeholders – until October 5.

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Javedullah Mehsud, the deputy commissioner of Kurram, said there had been no casualties since then and that the government was confident of reaching a resolution to end the conflict.

“This is unfortunately an ongoing land dispute in the area that has led to fighting in the past as well, but we are confident that we can put an end to it this time,” Mehsud told Al Jazeera.

So where is Kurram, what happened there, how did things escalate and what’s next?

Where is Kurram?

Kurram, a mountainous area that shares a long border with Afghanistan in the northwestern province of Khyber Pakhtunkhwa, is home to about 700,000 people, of which more than 42 percent belong to the Shia community.

It is closer to Afghanistan’s capital Kabul than any major city in Pakistan but also borders Afghanistan’s Khost, Paktia, Logar and Nangarhar provinces, which are considered havens for anti-Shia armed groups such as ISIL (ISIS) and the Pakistan Taliban (TTP).

The area has a history of sectarian conflict between the Shia and the Sunni majority groups and has also faced militancy during the past decade, with frequent attacks by TTP and other armed groups targeting the Shia community.

According to local authorities and tribal leaders, the current conflict has its roots in a continuing land dispute between Shia-majority and Sunni-majority tribes. Another similar incident flared up last year, resulting in the deaths of at least 20 people.

The Human Rights Commission of Pakistan (HRCP) urged the government to help broker peace in the area where, it added, “violence has taken a heavy toll on ordinary citizens”.

“HRCP calls on the KP government to ensure that the ceasefire being brokered, holds. All disputes, whether over land or born of sectarian conflict, must be resolved peacefully through negotiations convened by the KP government with all stakeholders represented,” it said in a statement on July 29.

HRCP is deeply concerned at the significant loss of life in #Parachinar , Kurram, where rival tribes have engaged in a violent land dispute for several days, fueling sectarian conflict. The violence has taken a heavy toll on ordinary citizens, whose freedom of movement and access… — Human Rights Commission of Pakistan (@HRCP87) July 29, 2024

What caused the latest clashes?

Mehmood Ali Jan, a member of the local peace committee and part of the jirga that held meetings this week, says that the conflict arose between Maleekhel, a Shia-majority tribe, and Madgi Kalay, a Sunni-majority tribe, over a tract of land in Boshehra village, situated 15km (9 miles) south of Parachinar city.

“It was a piece of agricultural land originally owned by the Shia tribe, which they had leased to the Sunni tribe for farming purposes. The lease was supposed to end this July, but when the time came, they refused to return the land, leading to fighting,” Jan told Al Jazeera.

Jan says that the local peace committee, which included members from both Shia and Sunni tribes, immediately tried to pacify the situation and asked the government to intervene. But the government, he says, was late to respond.

“The state was completely absent initially, leading to so much fighting. They did not interfere or send in forces or police despite the heavy presence of military and paramilitary personnel in the area,” Jan claimed.

Nisar Ahmad Khan, the district police officer, however, refutes the allegations of government inaction, saying that as soon as the fighting began, the state took swift action. He conceded, however, that a lack of manpower and the difficult terrain impeded the pace of the government’s response.

“We have limited capacity, and Kurram is a large, difficult area to access due to its mountainous terrain. Often, we had to hike for hours to reach places where fighting was taking place. Plus, due to the porous border with Afghanistan, many people have access to sophisticated weapons, making it even more difficult,” the police officer told Al Jazeera.

However, he categorically denied any involvement of TTP or any other armed group targeting the Shia community for their religious identity.

“The Boshehra village, where most of the fighting took place, has a strategic advantage for defenders, and anyone who tried to gain access was easily targeted. In this case, it was the Maleekhel tribe, which suffered more losses,” he said.

Why do such clashes keep happening?

Jan, the tribal elder, said even though a land dispute is at the heart of the current tensions, the region’s long history of sectarian strife allows “some elements” from both sides to use religion as a tool to mobilise.

“There have been major land dispute conflicts in the Kurram area between various tribes that have been ongoing since before the partition [of the Indian subcontinent in 1947]. Whenever anything triggers, it is conveniently given a sectarian angle, which is not the case,” he added.

There have been several incidents of significant sectarian violence in the last seven decades, but the most serious clash started in 2007, in which fighting between Shia and Sunni tribes lasted for almost four years. Several villages were set ablaze and thousands of people had to leave the region and seek shelter in other parts of the country.

Kurram, which was at the time part of the Federally Administered Tribal Areas (FATA), was cut off from the rest of the country. In 2011, the Pakistani military, with the help of local tribal elders, finally managed to put an end to the fighting. Government data shows nearly 2,000 people were killed in the clashes, while more than 5,000 people were reported injured.

Khan, the police chief said that in many areas of the district, Shia and Sunni communities live together peacefully.

He cited the Ashura procession last month, marked to mourn the martyrdom of Husayn Ibn Ali al-Hussein, the grandson of Prophet Muhammad.

“We recently had the Ashura processions, which were taken out in different parts of Kurram. In many areas, Sunni tribes provided security for Shias who were mourning,” Khan said.

Mehsud, the deputy commissioner, said the government hoped to use the ceasefire to resolve the land dispute between the Maleekhel and Madgi Kalay tribes.

“We have our land dispute resolution mechanisms, and this ceasefire will allow us to bring all stakeholders together to try to end this permanently,” he said.

What is the current situation?

The fighting led to the closure of most roads leading to Kurram, and news reports emerged that even ambulances were targeted by unknown men.

Schools in Parachinar remained closed, while markets saw little activity. Jan, who is also a trader, said the closure of roads led to shortages of food and other necessary items, making it difficult for anyone needing to leave town in case of an emergency.

“After the ceasefire, we are hoping that life returns to normal. Right now, people are travelling in convoys only, with police and paramilitary forces guarding the roads leading out of Kurram,” he said.

Jan also added that the fighting resulted in the closure of the mobile data network, but fixed lines were working.

Mehsud, the government official, said that after the pause in fighting, there is an uneasy calm in the area but he expressed hope that normal activity in the region should resume soon.

“Naturally, there is an air of fear right now, and people are reluctant to step out of their homes. However, in the last two days, we have seen some semblance of normalcy, and things should improve,” he said.