Alzheimer's disease (AD) is like a hidden "killer", silently eroding patients' cognition and daily life.
With the continuous deepening of research on this disease, we gradually realize the importance of early screening, early diagnosis, and early intervention in dealing with Alzheimer's Disease (AD). This article will take you to a deeper understanding of the pathological changes, diagnostic methods, and risk prediction of AD, providing strong support for safeguarding brain health.
The pathological changes of AD occur earlier than the appearance of clinical symptoms
With the deepening understanding of the disease, it has been discovered that characteristic pathological changes of Alzheimer's Disease (AD) can appear in the brain of patients 15 to 20 years before the clinical symptoms of AD emerge.
Meanwhile, the "Revised Diagnostic and Staging Criteria for Alzheimer's Disease (2024)" published by the Alzheimer's Association (AA) in 2024 categorizes Alzheimer's Disease (AD) into seven stages:
Stage 0: As long as there is a pathogenic gene for familial Alzheimer's Disease (AD), the individual is born with Stage 0 AD, which has neither clinical symptoms nor abnormalities in core biomarkers of AD;
Stage 1: The patient has no symptoms but exhibits abnormalities in core 1 biomarkers that are diagnostic of Alzheimer's Disease (AD);
Stage 2: The AD core 1 biomarker is abnormal, with subjective cognitive decline (SCD), and there may also be emotional changes, such as depression and anxiety, as well as mild psychiatric symptoms. Both Phase 1 and Phase 2 belong to the preclinical stage;
Stage 3: The patient develops mild cognitive impairment (MCI);
Stage 4: Mild dementia;
Stage 5: Moderate dementia;
Stage 6: Severe dementia;
Currently, AD remains incurable. As the disease progresses, patients gradually lose their ability to care for themselves, imposing a significant burden on their families.
Therefore, it is crucial to achieve early screening, diagnosis, and intervention for AD. The academic community also hopes to advance the intervention of AD disease progression to the mild cognitive impairment (MCI) stage3, or even the earlier subjective cognitive decline (SCD) stage4.
1. Specific markers help to accurately diagnose AD as early as possible
Alzheimer's Disease (AD) is a continuous pathophysiological process. Initially, AD-specific pathological changes occur in the brain of asymptomatic individuals, such as the deposition of amyloid beta (Aβ) to form senile plaques and the aggregation of tau protein to form neurofibrillary tangles. As the pathological changes continue to worsen, clinical symptoms gradually emerge and progress to dementia.
In the asymptomatic preclinical phase, AD-specific pathological changes have already occurred. Additionally, clinical syndromes associated with AD may also be caused by other non-AD diseases, making it impossible to accurately diagnose AD solely based on clinical manifestations. Therefore, precise diagnosis of AD based on specific biomarkers is of great significance.
The Revised Diagnostic and Staging Criteria for Alzheimer's Disease (2024) proposes that Alzheimer's Disease (AD) is defined by its biological characteristics, and therefore, biomarkers capable of accurately detecting AD pathological changes are sufficient to establish a diagnosis of the disease.
Therefore, when biomarkers can identify pathological changes in AD, the disease already exists, and the symptoms may appear after decades or even longer periods of disease progression. So specific markers for AD can help diagnose AD accurately as early as possible.
2. In the stage of normal cognition, abnormal biomarkers can predict risks
Previously, the risk of future cognitive impairment for individuals with normal cognitive function but abnormal AD biomarkers was unclear. However, a recent study published in The Lancet Neurology has provided an answer.
This study included a total of 5,158 participants with normal cognitive function and 700 participants with mild cognitive impairment (MCI) from Mayo Clinic for analysis between November 29, 2004 and December 2, 2024.
The study found that regardless of gender, whether APOEε4 is positive or negative, the risk of developing mild cognitive impairment and dementia throughout life increases with the increase in centiloid value (a unit for measuring the amount of amyloid (Aβ) deposition in Aβ-PET scans, with higher values indicating more deposition) (p<0.0001), making it the most influential predictive factor. That is, the greater the amount of amyloid deposition, the higher the risk of developing mild cognitive impairment and dementia.
The study also found that individuals with the APOE ε4 gene had a higher lifetime risk of mild cognitive impairment or dementia compared to those without the APOE ε4 gene (p<0.0001). The lifetime risk of mild cognitive impairment or dementia was higher in women than in men (p=0.0090). Among individuals with the same amount of amyloid deposition, women with the APOE ε4 gene had the highest lifetime risk of mild cognitive impairment and dementia, while men without the APOE ε4 gene had the lowest risk. For women with high amyloid deposition and the APOE ε4 gene, the risk of developing mild cognitive impairment over their lifetime exceeded 80%, indicating that this high-risk group has an extremely high probability of developing cognitive impairment.
In addition, under the same amount of amyloid deposition, younger individuals are more prone to develop dementia compared to older individuals (p<0.0001). This suggests that if there is significant amyloid deposition at a younger age, it should be taken seriously and vigilance should be maintained to prevent the development of dementia.
This study not only indicates that the amount of amyloid deposition is an important risk factor for Alzheimer's Disease (AD), which can be used to comprehensively assess the likelihood of developing AD in the future along with various risk factors (gender, genetics, age, etc.), but also provides an evaluation basis for subsequent ultra-early anti-amyloid treatment.
With the advancement of medicine, it is believed that in the future, by combining advanced examination methods such as Aβ-PET, early prediction, diagnosis, and preventive intervention can be achieved, thereby slowing down the occurrence and progression of Alzheimer's Disease (AD) and improving patients' quality of life.
Hainan Chengmei Hospital's Memory Clinic integrates professional resources from multiple fields to provide patients with comprehensive, precise, and personalized diagnosis and treatment services.
Expert Introduction
Dai Wenxin, Chief Physician
Executive Director of the Multidisciplinary Geriatric Diagnosis and Treatment Center
Professor, PhD candidate
Postdoctoral researcher, master's supervisor
Medical expertise:
I. Diagnosis and treatment of Alzheimer's disease and other geriatric diseases
II. Diagnosis and treatment of diseases across multiple disciplines, including respiratory system, cardiovascular system, nervous system, and geriatric diseases
III. Genetic diagnosis, chemotherapy, targeted therapy, immunotherapy, microenvironment analysis, and integrated precision treatment of tumors
IV. Genetic diagnosis and precision treatment of hypertension, hyperlipidemia, hyperuricemia, and hyperglycemia
V. New biomedical technologies such as stem cell and gene programming, as well as new technologies like insulin pumps and diabetes reversal
VI. High-intensity focused ultrasound (HIFU) for the treatment of benign and malignant tumors
VII. Microbial therapy of intestinal flora for chronic diseases and mental and psychological disorders
VIII. Diagnostic and therapeutic techniques under medical endoscopes such as bronchoscope, mediastinoscope, and thoracoscope
IX. Sleep medicine
X. Chronic disease management
Clinic Hours: Monday and Wednesday morning
Source | WeChat official account of Professor Han Ying's team at Xuanwu Hospital