How much do you know about Alzheimer's? It's closely related to education level, sleep, and even weight

Introduction:

my country is a country with a large population. As the population ages, the number of people suffering from neurodegenerative diseases is also increasing rapidly. According to statistics, there are more than 15 million people with Alzheimer's disease in my country.

In this issue, we are honored to talk with Professor Yu Jintai about the current understanding of Alzheimer's disease and future hopes. Professor Yu is the chief physician and professor of the Department of Neurology at Huashan Hospital Affiliated to Fudan University, and the executive deputy director of the Institute of Neurology at Fudan University. He has done in-depth research on Alzheimer's disease.

Professor Yu introduced that Alzheimer's disease is closely related to vascular risk factors, emotions, education level, and social activities. "Regular exercise, keeping the brain active, and ensuring good sleep are crucial to preventing Alzheimer's disease."

01 What are neurodegenerative diseases?

Q: What are the common neurodegenerative diseases?

Yu Jintai: Neurodegenerative diseases, also known as neurodegenerative diseases or neurodegenerative diseases, are diseases of the nervous system that are closely related to aging. Among them, the most common is Alzheimer's disease. In addition to Alzheimer's disease, there is Parkinson's disease, which is the second most common neurodegenerative disease.

Generally speaking, we divide neurodegenerative diseases into two categories: one is related to cognitive impairment, and the other is related to movement disorders, including Parkinson's disease, multiple system atrophy, etc. These diseases are collectively referred to as neurodegenerative diseases.

Q: What are the characteristics of this type of disease compared to other diseases in the body?

Yu Jintai: A notable feature of neurodegenerative diseases is that they are closely related to age. The incidence of these diseases gradually increases with age. Take Alzheimer's disease as an example. The prevalence rate is about 5% in people over 60 years old, but it may rise to nearly 20% in people over 70 years old, and it may reach 30% to 40% in people over 90 years old.

In addition, the main characteristics of this type of neurodegenerative disease are brain atrophy, neuronal degeneration and damage, which lead to loss of function and are generally irreversible. Currently, we cannot completely reverse its onset and development process, which is also one of the important challenges in research and treatment in this field.

Q: What are the current difficulties and challenges in researching and treating this type of disease?

Yu Jintai: These neurodegenerative diseases are age-related and have the characteristics of insidious onset and gradual progression. The onset often gradually worsens without notice, which makes early diagnosis very difficult.

On the other hand, these diseases mainly cause brain degeneration and atrophy, and neuronal loss, so when clinical symptoms are obvious, the structure of the brain has been severely damaged, such as atrophy, degeneration, or neuronal loss. There is currently no drug that can effectively reverse the pathological process of these diseases, so early diagnosis and better prevention strategies are crucial, but this is also a huge challenge.

02 What are the main symptoms of Alzheimer's disease?

Q: Next, we want to learn about a typical neurodegenerative disease, Alzheimer's disease. Can you tell us what kind of brain disease it is? What are its typical characteristics?

Yu Jintai: Alzheimer's disease, commonly known as senile dementia, is the most common neurodegenerative disease and the most common cause of dementia. About two-thirds of dementia cases are related to the degeneration of aβ protein. Like other neurodegenerative diseases, it is characterized by a process of causing the disease and then gradually progressing. Its incidence rate increases year by year with age.

Among the clinical manifestations of Alzheimer's disease, the most typical feature is episodic memory impairment: patients often forget what just happened, but can remember things from earlier years. As the disease progresses, in addition to memory problems, other cognitive dysfunctions such as language disorders, visual-spatial disorders, and calculation disorders may also occur.

In the late stages of the disease, patients may also experience mental problems and behavioral abnormalities, which have a serious impact on their quality of life. Another major pathological feature of Alzheimer's disease is the deposition of amyloid proteins in the brain and neuronal tangles caused by abnormal phosphorylation, which constitute the two core pathologies of the disease.

The two core pathologies provide the "gold standard" for the pathological diagnosis of Alzheimer's disease. Currently, the biological diagnosis and treatment of Alzheimer's disease mainly focus on the study of these two core pathologies, and a series of exploratory work has been carried out.

Q: What is the current trend in the prevalence of Alzheimer’s disease?

Yu Jintai: In fact, not only in China, but also in the world, Alzheimer's disease is showing a growth trend of doubling every 20 years.

This is mainly due to two main factors: on the one hand, as mentioned above, this type of disease is closely related to age, and the current society is experiencing an aging process, so the incidence of Alzheimer's disease is gradually increasing. On the other hand, the more important reason is the improvement of the quality of life and the gradual extension of human life span, which also leads to an increased risk of Alzheimer's disease.

In addition, there are other risk factors to consider, including cardiovascular and cerebrovascular diseases and related vascular metabolic diseases. The increasing number of these factors has also indirectly led to the increasing incidence of Alzheimer's disease year by year.

03 Several hypotheses on the causes of Alzheimer’s disease

Q: Alzheimer's disease is a very complex disease. What are the current hypotheses about the cause of Alzheimer's disease?

Yu Jintai: Regarding Alzheimer's disease, its pathogenesis is actually very complex, and the cause has not yet been fully clarified. Of course, there are many different hypotheses, including the amyloid cascade hypothesis, the abnormal tau phosphorylation hypothesis, and hypotheses involving infection, inflammation, calcium homeostasis disorders, and cholinesterase. In general, the most recognized one is the amyloid cascade hypothesis.

The hypothesis holds that amyloid proteins, especially aβ proteins, abnormally increase and misfold in the brain, forming senile plaques in the brain. This phenomenon triggers a series of downstream amyloid protein cascade reactions, leading to abnormal tau phosphorylation, which in turn leads to neuronal degeneration, damage and apoptosis, and ultimately brain atrophy. When it reaches a certain level, it affects various brain functions, especially memory function, resulting in clinical symptoms of the disease.

Q: What other hypotheses are there about the cause of Alzheimer's disease? Can you introduce them?

Yu Jintai: The most important research hypothesis is still the amyloid protein cascade hypothesis. In addition, the abnormal phosphorylation hypothesis of tau is becoming more and more common.

It is particularly noteworthy that the amyloid cascade hypothesis currently dominates the field of Alzheimer's disease-related drug development, and many drug studies are based on this.

This hypothesis is mainly proposed for some special familial Alzheimer's disease, which will cause mutations in the gene that produces related amyloid proteins. This abnormality leads to excessive accumulation of amyloid proteins in the brain, and eventually leads to the onset of Alzheimer's disease after a certain age. Therefore, the amyloid cascade hypothesis is currently recognized.

04 How can we diagnose Alzheimer’s disease early?

Q: How is Alzheimer's disease diagnosed currently?

Yu Jintai: There are now more and more options for diagnostic methods and tools for Alzheimer's disease.

First, we have diagnostic criteria, which are constantly evolving. In the past, Alzheimer's disease was often viewed as a clinical syndrome. We typically examined it by first determining if the patient had symptoms of dementia, then observing if they met the typical features of Alzheimer's disease, and finally excluding other potential causes of dementia. These steps can be used to diagnose Alzheimer's disease.

However, there are some problems. On the one hand, it is difficult to achieve early diagnosis because it is usually not diagnosed until the disease has progressed to the dementia stage, at which point the best time for intervention has often been missed.

On the other hand, the accuracy of clinical diagnosis is not very high. Of course, the gold standard for Alzheimer's disease is to make a pathological diagnosis by autopsy pathological observation to determine whether there is amyloid deposition and abnormal phosphorylation of tau protein to form neurofibrillary tangles. In contrast, the accuracy of clinical diagnosis is only 70% to 80%.

In view of the above shortcomings and challenges, the diagnostic criteria for Alzheimer's disease are constantly evolving and being revised. These evolutions and revisions are mainly based on the research progress of specific biomarkers related to Alzheimer's disease. In particular, we can now diagnose by detecting biomarkers of amyloid problems and abnormal tau phosphorylation in cerebrospinal fluid.

In addition, molecular imaging techniques, such as amyloid PET and tau PET, allow us to more accurately detect amyloid in the brain. Therefore, the current diagnostic criteria have expanded the positioning of Alzheimer's disease from the previous clinical syndrome to the clinical and biological level. This means that we can consider a series of clinical manifestations as well as some biological indicators to make a more accurate diagnosis.

We can divide the diagnosis of Alzheimer's disease into three different stages: preclinical, cognitive impairment, and dementia.

Recently, the latest version of the diagnostic criteria was released at the Alzheimer's Disease International Conference. This latest version completely defines Alzheimer's disease as a biological entity, and as long as an individual detects signs of amyloid deposition and abnormal tau phosphorylation in the brain, he or she is considered to have Alzheimer's disease.

05What are the factors that lead to Alzheimer’s disease?

Question: What factors are currently known to be closely related to Alzheimer's disease? How much influence do genetic and environmental factors have on Alzheimer's disease?

Yu Jintai: As for Alzheimer's disease, we actually divide it into two categories. One is called familial Alzheimer's disease, which has a relatively low incidence rate of about 1% to 5%. It is usually related to specific genetic gene mutations. These gene carriers will develop the disease after reaching a certain age. The other is sporadic Alzheimer's disease. About 95% of Alzheimer's disease is sporadic, and its onset is the result of the interaction between genes and environmental factors. Studies have shown that genetic factors account for about 40% of the risk of disease, while environmental factors may account for about 60%.

Q: Can you briefly introduce the environmental factors that are currently known to be closely related to Alzheimer's disease, such as lifestyle habits, eating habits, etc.?

Yu Jintai: Currently, the more clear factors include lifestyle habits, such as exercise, sleep, cognitive activities and social interaction. These factors play a very important role in improving cognitive function and preventing dementia.

In addition, vascular risk factors are also very critical, including diabetes, hypertension, cardiovascular and cerebrovascular diseases, and even hypotension can significantly increase the risk of Alzheimer's disease.

Other factors include emotional problems, such as depression, which can also significantly increase the risk of Alzheimer's disease. In addition, abnormalities in homocysteine ​​levels and other metabolic markers have also been associated with an increased risk of the disease.

Education level is also a very important factor, and studies have shown that the higher the level of education, the lower the risk of developing the disease in the future.

06 Is there a cure for Alzheimer’s disease?

Q: In recent years, there have been remarkable advances in Alzheimer’s research and drug development. Can you briefly analyze the breakthroughs made in the past few years?

Yu Jintai: One of the most significant breakthroughs involves drug development based on the amyloid cascade hypothesis, which holds that abnormal production and deposition of amyloid plays a key role in the pathogenesis of Alzheimer's disease. Given the importance of amyloid in the pathological process, researchers have developed a series of selective antibodies that can selectively clear amyloid in the brain and have achieved promising results.

First, the results of the Phase III clinical trial of the monoclonal antibody last year were very impressive, and it received unconditional approval for marketing in the United States in July this year.

In addition, another similar product has also achieved very good results in the Phase III trial. If all goes well, it is expected to be approved for marketing in the second half of this year.

So this class of drugs is different from the drugs of the past, which were mainly related to neurotransmitters, but now we have monoclonal antibodies that can clear toxic amyloid in the brain, and combined with neurotransmitter drugs, it may have a positive effect on reducing the occurrence of this disease.

Question: Will there be new directions in the treatment of Alzheimer's disease in the future?

Yu Jintai: Regarding the future treatment of Alzheimer's disease, I just mentioned the major breakthroughs made in the past few years, which are mainly concentrated in the research field of the amyloid cascade hypothesis. Another major core pathology is the abnormal phosphorylation of tau protein, which leads to the formation of neuronal tangles, which is also a very important pathological process. Therefore, many new drugs have been developed in this field and have made breakthrough progress. These drugs can inhibit the abnormal phosphorylation of tau protein, thereby delaying the course and progression of the disease. For the pathological research surrounding tau protein, we have reason to believe that there will be major breakthroughs in the future.

Of course, for Alzheimer's disease, the two core pathologies mentioned above are both crucial. In the future, whether we can combine the treatment of clearing amyloid protein in the brain and inhibiting related tau protein problems to clear abnormal tau protein tangles in the brain may play a more important role in delaying and developing the disease.

07 For the public, how to prevent Alzheimer's disease

Q: How should the general public prevent Alzheimer's disease?

Yu Jintai: This question is also the most prominent feature of our team and our greatest contribution to Alzheimer's research. First, we conducted a study on the adjustable risk factors for Alzheimer's disease and identified multiple adjustable risk factors related to Alzheimer's disease.

Subsequently, we worked with international experts to develop an evidence-based prevention guideline for Alzheimer's disease, aiming to reduce the occurrence and progression of the disease. So how do we prevent it? In this study, we made 21 recommendations, 19 of which were considered worthy of recommendation, while two were not recommended.

One of the main recommendations is to focus on lifestyle, including regular physical exercise, keeping the brain active, ensuring good sleep and emotional health, which are important in preventing Alzheimer's disease. In addition, lifelong learning and active social interaction are also believed to help reduce the risk.

In addition to lifestyle, controlling blood pressure and blood sugar is also considered crucial, as is avoiding brain damage and trauma. In addition, preventing stroke is also an important aspect of Alzheimer's risk management.

Other relevant factors include heart health, especially atrial fibrillation, as they are closely related to the development and progression of Alzheimer's disease.

Depression is also considered an important risk factor, so maintaining a good emotional state is also very important to prevent the occurrence of Alzheimer's disease. In addition, the control of homocysteine ​​levels is also recommended, and some trace elements such as vitamin C can be appropriately supplemented.

In addition, there are two recommendations that are not recommended. One is to use estrogen replacement therapy to prevent Alzheimer's disease. Related clinical trials have failed. Clinical trials have shown that this method not only cannot prevent, but will increase the risk of Alzheimer's disease. We also clearly do not recommend the use of cholinesterase inhibitors to prevent the disease, because these drugs can only improve symptoms, but cannot prevent it.

Finally, weight management was also highlighted as an important factor. Being too fat or too thin is not good for your health.

This article is a work supported by Science Popularization China Starry Sky Project

Team/Author: Deep Science

Reviewer: Chen Hai (Xu, deputy director of PLA General Hospital (301 Hospital), postgraduate tutor)

Produced by: China Association for Science and Technology Department of Science Popularization

Producer: China Science and Technology Press Co., Ltd., Beijing Zhongke Xinghe Culture Media Co., Ltd.

Source: Deep Science