How to realize the early diagnosis and treatment of Alzheimer's disease

*Only for medical professionals to read for reference.
Early screening, accurate diagnosis, early treatment, home care
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 Alzheimer's disease (AD) seriously affects the physical and mental health of patients.
With the increasing aging of our country's population, AD is about to become a severe public health problem facing our country
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Although the etiology and pathogenesis of AD are complex and have not yet been clarified, it has always been a consensus in the academic community that AD patients should be diagnosed as early as possible, so as to provide opportunities for early intervention
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 However, due to the public's lack of a comprehensive understanding of AD and the lack of effective treatment methods in the past, the early diagnosis and treatment of AD in China is not ideal, and many problems still need to be solved to promote related work
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The “medical community” specially invited Professor Chen Xiaochun, Secretary of the Party Committee of Fujian Medical University, Professor Ye Qinyong, and Professor Pan Xiaodong of Fujian Medical University Affiliated Union Hospital, to interpret the pathogenesis of AD and explore the latest developments, and the practical reasons and early stages that restrict the early diagnosis and treatment of AD in China The importance of intervention in AD and other related topics of concern to clinicians and the public
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Q.
What is the progress in solving the mystery of AD pathogenesis? With regard to the latest progress in the exploration of AD pathogenesis, Professor Chen Xiaochun first introduced, "The β-amyloid (Aβ) cascade hypothesis is still the dominant AD pathogenesis theory, that is, the abnormal metabolism of Aβ leads to an increase in its production.
It triggers changes in tau protein hyperphosphorylation, neuronal damage, and oxidative stress, and ultimately leads to cognitive impairment
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Parallel to the Aβ cascade hypothesis is the tau protein pathogenic theory.
The current view is that the accumulation of tau protein causes intracellular nerves Fibrillary tangles cause more direct damage to neurons
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"However, Professor Chen Xiaochun also admitted that the pathogenesis of AD is complex, and the above two mainstream hypotheses still cannot fully explain the pathogenesis of AD
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In recent years, neuroimmune pathways have been a hot spot in the pathogenesis of research.
For example, abnormal peripheral immunity leads to excessively activated immune cells infiltrating the center.
Nervous system damage neuron hypothesis
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In addition, the unfolded protein response leads to the imbalance of endoplasmic reticulum homeostasis, which damages insulin and its signal transduction pathways and affects cognitive function.
It is also one of the hypotheses that have been put forward
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Ask why most AD patients do not Can be diagnosed and treated early? From pathophysiological changes such as abnormal Aβ generation to obvious symptoms of cognitive impairment, patients may experience a long asymptomatic period of 20-30 years.
Professor Chen Xiaochun pointed out that this is because of the patient’s brain structure and There are still sufficient reserves of functions to cope with the functional damage caused by the disease.
No obvious clinical manifestations appear until AD destroys 80%-90% of the relevant neurons.
At this time, the disease of AD patients has progressed to a more serious state
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 Currently internationally AD is divided into three stages, namely, the preclinical stage with only biomarker changes and no obvious symptoms; the mild cognitive impairment (MCI) stage with certain cognitive impairment symptoms; the clinical manifestation stage with obvious symptoms, and According to the patient’s condition, it is divided into mild/moderate/severe AD
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According to
 Professor Ye Qinyong, in the pre-clinical and MCI phases, three important signals can warn AD patients to go to the specialist clinic as soon as possible for treatment: 1) forgetting recent memory; 2) Situational memory disorder; 3) Impairment of language function and significant changes in mood, manifested as verbal narration, depression/anxiety/indifference or weird mental state, etc.
Early consultation may help delay the progression of the disease
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 Professor Pan Xiaodong believes that patients should be paid attention to The role of family members in monitoring or screening for AD, because family members can recognize the possible early clinical manifestations of patients at close range
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For high-risk AD groups with APOE mutations and family history of AD, they can also pass science education to family members.
Change the living habits of high-risk groups and reduce factors that accelerate disease progression
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Ask how to do a good job in the early diagnosis and treatment of AD? Due to the lack of obvious manifestations of patients in the pre-clinical stage of AD, in this theoretical period when there are opportunities for early intervention, it is more challenging to achieve early diagnosis and treatment
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Professor Chen Xiaochun believes that the "AD-derived MCI" phase, which generally lasts for 2-6 years, is also a "golden time window" for early diagnosis and early treatment of AD.
The modeling research results show that if effective treatment can be achieved at this stage, Delaying the progression of patients from MCI to AD for five years can reduce the number of AD patients by about 50%, which is undoubtedly extremely significant
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Domestic scholars have formulated an expert consensus for the diagnosis and treatment of AD-derived MCI, which is expected to be officially published soon
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 Traditional AD diagnosis methods mainly include various classic scale tests for cognitive function, living ability, mental state, and some imaging aids.
However, Professor Ye Qinyong introduced that in recent years, the biomarker diagnosis of AD has made breakthroughs.
Corresponding diagnostic criteria for ATN have been proposed, namely Aβ (A), pathological tau (T), and neurodegeneration (N), of which Aβ positive is the first and necessary condition, and molecular imaging detection, blood or cerebrospinal fluid detection around Aβ and tau Even genetic diagnosis is developing rapidly, and structural imaging is helpful in assessing neurodegeneration
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 Professor Pan Xiaodong further added the latest advances in AD biomarker diagnosis, “The diagnosis of AD biomarkers has a bright future, especially based on the non-invasive and rapid detection of body fluids, and the clinical transformation may be just around the corner
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The
current specific detection indicators are fully involved "ATN", such as Aβ42/Aβ40, phosphorylated tau (p-tau)-217/231/181 are commonly detected objects, they can be used to distinguish AD from other neurodegenerative diseases, and can also provide precision treatment in the future Targets, and markers suggesting neurodegeneration include neurofilament protein, total tau, etc.
, which can be used to assess disease dynamics and drug efficacy
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"A good early diagnosis of AD is possible to achieve early treatment.
When it comes to the current treatment plan for AD, Professor Ye Qinyong said that the existing treatment plan is still centered on the pathogenesis hypothesis, such as the Aβ hypothesis, the tau hypothesis and the traditional bile hypothesis.
Alkaliergic/glutamatergic hypothesis, etc.
, among which cholinesterase inhibitors such as donepezil for the cholinergic pathway and memantine for the glutamatergic pathway are currently more representative therapeutic drugs, but "these drugs only improve cognitive or behavioral and psychological symptoms of patients, and is only effective in patients with mild AD, not through the intervention of Aβ or tau, modify disease progression of AD "
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 However, in the treatment of AD, family care and other non-pharmacological methods can Play an important role
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Professor Pan Xiaodong believes that the care of AD patients at different stages of the disease should have their own focus, and when caring for early patients, cognitive rehabilitation treatment plans should be developed as much as possible, and targeted to strengthen training or compensation, and intervene in the emergence of patients.
The cognitive domain of functional impairment is “what is missing to make up for what
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 The greatest hope for achieving better early diagnosis and treatment, and truly changing the course of AD disease, is new drugs targeting pathological proteins such as Aβ or tau, said Professor Xiaochun Chen "The lack of effective treatment is the biggest shortcoming that has restricted the treatment of AD in the past.
In 2021, monoclonal antibodies targeting Aβ have been approved abroad.
This milestone event is expected to bring new treatment hopes for AD patients
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"Summary: With the continuous progress of basic scientific research and drug development, the mysterious pathogenesis of AD is being solved in a way of solving the mystery, precise intervention and effective treatment are no longer far away, but in order to achieve better treatment effects, it is still necessary to try to be as early as possible in the course of the disease.
In the “golden time window”, we found and diagnosed AD patients who did not have obvious brain structure damage and cognitive impairment, and with good early diagnosis and treatment, we will strive for more possibilities for the future
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Expert profileProfessor Chen Xiaochun, Secretary of the Party Committee of Fujian Medical UniversityProfessor, chief physician, and doctoral supervisor of the Department of Neurology, Fujian Medical University Union Hospital, Member of the New Medical Department Construction Working Group of the Ministry of EducationVice Chairman of Fujian Science and Technology Association, President of Fujian Medical Doctor Association Chinese Medical Doctor Association Executive Director, Vice President of the Branch of Neurologists, Head of the Dementia and Cognitive Disorders Group of the Neurology Branch of the Chinese Medical Association, National Health Commission has outstanding contributions, young and middle-aged experts, National New Century Talents Project, National Candidate, National Excellent Science and Technology Professor Ye Qinyong, chief physician, professor, and doctoral supervisor of the Department of Neurology, Union Hospital of Fujian Medical University Member, International Society for Parkinson's Disease and Movement Disorders (MDS), Vice President of Cognitive Disorder Branch of Chinese Society of Gerontology, Executive Director of China Neuromodulation Alliance, Editorial Board Member of "Chinese Journal of Neurology", "Chinese Clinical Neuroscience", Fujian Deputy Chairman of the Provincial Neurologist Branch, Deputy Chairman of the Neurology Branch of the Fujian Medical Association and Leader of the Neurodegenerative Diseases Group, Deputy Director of the Quality Control Committee of Fujian Neurocognition and Movement Disorders, Deputy Director of the Fujian Association of Integrated Traditional Chinese and Western Medicine Neurology Chairman, Member of the Neurology Group of the Chinese Geriatrics Branch, Member of the Standing Committee of the Neurodegenerative Disease Branch of the Chinese Microcirculation Society and Deputy Group Leader of the ATN Group, Member of the Standing Committee of the Vascular Cognitive Impairment Branch of the Chinese Stroke Society, Neurocognition of the Alzheimer's Disease Prevention and Treatment Association Member of the Standing Committee of the Disability Professional Branch, Member of the Standing Committee of the Parkinson's Special Committee of the Chinese Rehabilitation Society, and Member of the Standing Committee of the Chinese Integrated Traditional Chinese and Western Medicine Neurology Professional Committee Professor Pan Xiaodong Chief physician, professor and doctoral supervisor of the Neurology Department of Fujian Medical University Union Hospital Chairman of the First Chairman of the Rehabilitation Professional Committee of Cognitive Disorders, Fujian Association of Rehabilitation Medicine, Deputy Chairman of the Professional Committee of Immunology and Translational Medicine, Fujian Society of Immunology, Secretary of the Dementia and Cognitive Disorders Group, Neurology Branch of Chinese Medical Association, Neuroscience, Chinese Society of Neuroscience Member of the Transgender Branch Member of the Neuropsychology and Behavioral Neurology Group of the Neurology Branch of the Chinese Medical Association Committee Member, Deputy Leader of Neurodegeneration Group, Fujian Neurology Branch, National Institutes of Health (NIH)/National Institute of Aging (NIA) Postdoctoral fellow *This article is only used to provide scientific information to medical and health professionals and does not represent platform views