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*It is only for medical professionals' reference and reading.
The road is long and long, and I will look up and down
.
Alzheimer's disease (AD) is the most common neurodegenerative disease.
It has a long course of disease and a high disability rate, which seriously affects the quality of life of patients and brings serious mental and economic burdens to patients' families and society
.
Facing AD patients: Why do drug treatments fail repeatedly? What kind of exploration should we carry out in failure? What strategy should be adopted for the treatment of AD? These are the problems that our clinicians should think about and solve
.
At the 7th China Dementia and Cognitive Disorder Academic Conference of the Chinese Medical Association Neurology Branch, Professor Jia Jianping from the Department of Neurology, Xuanwu Hospital, Capital Medical University, gave a wonderful topic on "Alzheimer's Disease Mechanism and Strategic Thinking" Report
.
01 China is a big country with dementia, and about 50 million people suffer from cognitive impairment-related diseases.
Figure 1: Update China's mild cognitive impairment and dementia data in 2020.
In 2020, a series of studies by Professor Jia Jianping’s team found that dementia among people over 60 years old in China The prevalence rate is 6.
04%.
The total number of patients with mild cognitive impairment and dementia is about 53 million.
The average annual expenditure for dementia patients is 120,000 yuan, and the total annual expenditure is nearly 2 trillion yuan
.
1.
From the perspective of time: since 1990, the age stratification of dementia has shown a trend of increasing with age, suggesting that an aging society has contributed to the increase in the prevalence of dementia
.
2.
From a geographical point of view: China's dementia is low in the south, high in the north, and high in the west, with rural areas higher than urban areas
.
The series of research results of Professor Jia Jianping’s team were published in famous journals such as Lancet Neurology (IF: 30.
039) and The Lancet Public Health (IF: 16.
292).
These research results suggest that, as a populous country, China has the highest number of patients with dementia in the world As China’s population ages, the prevalence of dementia and medical expenditure will continue to rise
.
02 Why does AD medication fail repeatedly? Although there are more and more researches on AD drugs, the results are not satisfactory.
Why do AD drug treatments fail again and again, what are the reasons for this, and what thinking does it bring us? ■ Global Alzheimer's disease treatment drug research and development status Figure 2: AD drug research and development pipeline in 2020 worldwide, AD new drugs are in different stages of research and development
.
Treatment drugs for AD are mainly divided into two aspects, one is disease-modifying drugs, and the other is disease diagnosis and treatment drugs.
Among them, disease-modifying drugs are the focus of AD drug research and development
.
Currently, there are a total of 121 drugs in the pipeline
.
Among them, there are 29 drugs in phase III, 65 drugs in phase II, and 27 drugs in phase I.
The proportions of disease-modifying drugs (phase III/II/II) are 59%, 85%, and 93%, respectively
.
■ The multiple mechanisms of AD determine that it is not suitable for single-factor treatment.
Figure 3: AD is not suitable for single-factor treatment.
We know that the pathogenesis of AD includes many aspects: Aβ production and Aβ oligomers, Tau protein structure and function abnormal mechanisms, and inflammatory mechanisms The regulation and vascular injury mechanism of serotonin are all involved in the occurrence and development of AD
.
At present, most of the drugs for AD are to prevent a single link in the pathogenesis of AD
.
In clinical trials of AD, the Aβ hypothesis is the most based, accounting for 22.
3%; followed by the neurotransmitter hypothesis, accounting for 19.
0%; the tau spreading hypothesis, accounting for 12.
2%, and the vascular injury mechanism hypothesis, accounting for 6%
.
Most of these clinical trials for the single-morbidity hypothesis ended in failure, suggesting that the development of multi-targeted drugs may be a new direction for AD treatment
.
■ There may be ethnic differences in the mechanism of AD Figure 4: APOE gene carrying status in China The 2019 series of studies by Professor Jia Jianping’s team found that China’s APOE gene carrying status is different from that of Europe and the United States.
The prevalence of APOE-positive genotypes in China is significantly lower than that of patients in Europe and the United States.
It reminds us that ethnic background is an important factor in the risk of AD
.
Figure 5: AD animal model In the same year, Professor Jia Jianping's team constructed its own nationalized AD animal model to reveal the new mechanism of AD
.
It was found that the research and development of AD drugs for different races should focus differently, and it was found that traditional Chinese medicine monomers and magnolol, sulforaphane, and Polygala saponins have therapeutic effects on AD
.
03 New direction of AD diagnosis and treatment: accurate diagnosis of asymptomatic stage ■ The identification of AD asymptomatic stage is very important.
Figure 6: The occurrence and development of AD is a continuous process.
From the pathological change of AD to the appearance of clinical symptoms, it is a continuous disease process.
15-before AD symptoms occur Pathophysiological changes began to appear in 20 years, seeking accurate diagnosis in the asymptomatic stage, and then intervention can determine the effect of getting twice the result with half the effort
.
■ The diagnosis of AD in the asymptomatic period depends on peripheral markers.
Figure 7: The AD peripheral blood markers Professor Jianping Jia’s team found for the first time in the world that the diagnostic effect of exosomes Aβ/Tau in peripheral blood is equivalent to that of cerebrospinal fluid.
It has found a new way to relieve patients’ pain instead of cerebrospinal fluid examination Method
.
And for the first time in the world, it was discovered that the synaptic protein of peripheral blood exosomes can predict AD 5-7 years in advance, gaining time for ultra-early intervention and making prevention of AD a reality
.
04 Anchor high-risk populations for AD prevention Figure 8: China's Alzheimer's disease primary prevention guideline In 2020, Professor Jia Jianping's team was invited by Lancet Neurology to discuss the current situation and prevention and control strategies of China's dementia to the world, and jointly formulated it with many hospitals "China Guidelines for the Primary Prevention of Alzheimer's Disease", the guidelines introduce that there are 9 controllable and 3 uncontrollable risk factors for AD, which provides a basis for the formulation of dementia intervention strategies
.
The 9 controllable factors are: cerebrovascular disease, cardiovascular disease, diabetes, dyslipidemia, overweight or obesity, smoking, harmful drinking, marital status (divorced or widowed is more likely to be AD), education level (<4 years is more likely to be AD)
.
The three uncontrollable factors are: family history, female, and age
.
Controlling controllable factors, anchoring high-risk groups for AD prevention, and early recognition of AD symptoms are important directions for AD prevention and treatment
.
Key points 1.
China's aging has ushered in a huge population of dementia; 2.
The lack of breakthrough progress in dementia treatment may be due to the single treatment target and the failure of the key mechanism to grasp the core, and the research on the key mechanism should pay attention to the ethnic differences of our people 3.
Early treatment of dementia without disease is a smart strategy, and accurate diagnosis of asymptomatic period depends on peripheral markers; 4.
Dementia can be prevented
.
The road is long and long, and I will look up and down
.
Alzheimer's disease (AD) is the most common neurodegenerative disease.
It has a long course of disease and a high disability rate, which seriously affects the quality of life of patients and brings serious mental and economic burdens to patients' families and society
.
Facing AD patients: Why do drug treatments fail repeatedly? What kind of exploration should we carry out in failure? What strategy should be adopted for the treatment of AD? These are the problems that our clinicians should think about and solve
.
At the 7th China Dementia and Cognitive Disorder Academic Conference of the Chinese Medical Association Neurology Branch, Professor Jia Jianping from the Department of Neurology, Xuanwu Hospital, Capital Medical University, gave a wonderful topic on "Alzheimer's Disease Mechanism and Strategic Thinking" Report
.
01 China is a big country with dementia, and about 50 million people suffer from cognitive impairment-related diseases.
Figure 1: Update China's mild cognitive impairment and dementia data in 2020.
In 2020, a series of studies by Professor Jia Jianping’s team found that dementia among people over 60 years old in China The prevalence rate is 6.
04%.
The total number of patients with mild cognitive impairment and dementia is about 53 million.
The average annual expenditure for dementia patients is 120,000 yuan, and the total annual expenditure is nearly 2 trillion yuan
.
1.
From the perspective of time: since 1990, the age stratification of dementia has shown a trend of increasing with age, suggesting that an aging society has contributed to the increase in the prevalence of dementia
.
2.
From a geographical point of view: China's dementia is low in the south, high in the north, and high in the west, with rural areas higher than urban areas
.
The series of research results of Professor Jia Jianping’s team were published in famous journals such as Lancet Neurology (IF: 30.
039) and The Lancet Public Health (IF: 16.
292).
These research results suggest that, as a populous country, China has the highest number of patients with dementia in the world As China’s population ages, the prevalence of dementia and medical expenditure will continue to rise
.
02 Why does AD medication fail repeatedly? Although there are more and more researches on AD drugs, the results are not satisfactory.
Why do AD drug treatments fail again and again, what are the reasons for this, and what thinking does it bring us? ■ Global Alzheimer's disease treatment drug research and development status Figure 2: AD drug research and development pipeline in 2020 worldwide, AD new drugs are in different stages of research and development
.
Treatment drugs for AD are mainly divided into two aspects, one is disease-modifying drugs, and the other is disease diagnosis and treatment drugs.
Among them, disease-modifying drugs are the focus of AD drug research and development
.
Currently, there are a total of 121 drugs in the pipeline
.
Among them, there are 29 drugs in phase III, 65 drugs in phase II, and 27 drugs in phase I.
The proportions of disease-modifying drugs (phase III/II/II) are 59%, 85%, and 93%, respectively
.
■ The multiple mechanisms of AD determine that it is not suitable for single-factor treatment.
Figure 3: AD is not suitable for single-factor treatment.
We know that the pathogenesis of AD includes many aspects: Aβ production and Aβ oligomers, Tau protein structure and function abnormal mechanisms, and inflammatory mechanisms The regulation and vascular injury mechanism of serotonin are all involved in the occurrence and development of AD
.
At present, most of the drugs for AD are to prevent a single link in the pathogenesis of AD
.
In clinical trials of AD, the Aβ hypothesis is the most based, accounting for 22.
3%; followed by the neurotransmitter hypothesis, accounting for 19.
0%; the tau spreading hypothesis, accounting for 12.
2%, and the vascular injury mechanism hypothesis, accounting for 6%
.
Most of these clinical trials for the single-morbidity hypothesis ended in failure, suggesting that the development of multi-targeted drugs may be a new direction for AD treatment
.
■ There may be ethnic differences in the mechanism of AD Figure 4: APOE gene carrying status in China The 2019 series of studies by Professor Jia Jianping’s team found that China’s APOE gene carrying status is different from that of Europe and the United States.
The prevalence of APOE-positive genotypes in China is significantly lower than that of patients in Europe and the United States.
It reminds us that ethnic background is an important factor in the risk of AD
.
Figure 5: AD animal model In the same year, Professor Jia Jianping's team constructed its own nationalized AD animal model to reveal the new mechanism of AD
.
It was found that the research and development of AD drugs for different races should focus differently, and it was found that traditional Chinese medicine monomers and magnolol, sulforaphane, and Polygala saponins have therapeutic effects on AD
.
03 New direction of AD diagnosis and treatment: accurate diagnosis of asymptomatic stage ■ The identification of AD asymptomatic stage is very important.
Figure 6: The occurrence and development of AD is a continuous process.
From the pathological change of AD to the appearance of clinical symptoms, it is a continuous disease process.
15-before AD symptoms occur Pathophysiological changes began to appear in 20 years, seeking accurate diagnosis in the asymptomatic stage, and then intervention can determine the effect of getting twice the result with half the effort
.
■ The diagnosis of AD in the asymptomatic period depends on peripheral markers.
Figure 7: The AD peripheral blood markers Professor Jianping Jia’s team found for the first time in the world that the diagnostic effect of exosomes Aβ/Tau in peripheral blood is equivalent to that of cerebrospinal fluid.
It has found a new way to relieve patients’ pain instead of cerebrospinal fluid examination Method
.
And for the first time in the world, it was discovered that the synaptic protein of peripheral blood exosomes can predict AD 5-7 years in advance, gaining time for ultra-early intervention and making prevention of AD a reality
.
04 Anchor high-risk populations for AD prevention Figure 8: China's Alzheimer's disease primary prevention guideline In 2020, Professor Jia Jianping's team was invited by Lancet Neurology to discuss the current situation and prevention and control strategies of China's dementia to the world, and jointly formulated it with many hospitals "China Guidelines for the Primary Prevention of Alzheimer's Disease", the guidelines introduce that there are 9 controllable and 3 uncontrollable risk factors for AD, which provides a basis for the formulation of dementia intervention strategies
.
The 9 controllable factors are: cerebrovascular disease, cardiovascular disease, diabetes, dyslipidemia, overweight or obesity, smoking, harmful drinking, marital status (divorced or widowed is more likely to be AD), education level (<4 years is more likely to be AD)
.
The three uncontrollable factors are: family history, female, and age
.
Controlling controllable factors, anchoring high-risk groups for AD prevention, and early recognition of AD symptoms are important directions for AD prevention and treatment
.
Key points 1.
China's aging has ushered in a huge population of dementia; 2.
The lack of breakthrough progress in dementia treatment may be due to the single treatment target and the failure of the key mechanism to grasp the core, and the research on the key mechanism should pay attention to the ethnic differences of our people 3.
Early treatment of dementia without disease is a smart strategy, and accurate diagnosis of asymptomatic period depends on peripheral markers; 4.
Dementia can be prevented
.
