Renji Alzheimer's Disease Neuroimaging Cohort Study

Alzheimer disease (AD) is the most common cognitive impairment disease, which is mainly manifested in memory loss, language function and logical thinking disorder, and ultimately leads to the loss of independent living ability of patients. China has become the country with the largest number of AD patients in the world. At present, it has reached more than 8 million. The AD incidence rate of the elderly over 65 years old is 4%-6%, which seriously affects the health of the elderly. At present, the medicines used in clinical practice are only symptomatic treatment, and have no effect on reversing the course of disease. Studies have shown that AD has a preclinical period of more than 10 years. In this period, patients have specific pathological changes in the brain, but there are no obvious clinical symptoms. However, if the intervention is started after significant cognitive impairment, irreversible changes have taken place in the brain, and the intervention effect is limited. In recent years, many drug clinical studies on ad specific pathophysiological processes have not achieved positive results, which may be one of the important reasons why the study failed to include subjects in the early stage of the disease.

In this context, in 2011, the National Institute of Aging and the Alzheimer's Association (NIA-AA) developed diagnostic criteria for preclinical AD, mild cognitive impairment (MCI) due to AD, and dementia due to AD, which are based on AD specific biomarkers, transform the prenatal diagnosis of AD from clinical symptomatology architecture to central biomarker architecture (gold standard). The latter refers to β Amyloid protein（Aβ), Phosphorylated tau (p-tau) and secondary neurodegenerative injury (neurodegeneration), the so-called AT(N) architecture, in which "A" and "T" are AD specific lesions, and "A" is the earliest landmark change. Through in vivo detection of AD specific central markers to identify AD as early as possible and carry out targeted intervention, it is expected to provide the possibility for AD reversal. On the other hand, it is well known that AD tends to occur in the elderly, and there are often small vessel disease (SVD) coexisting in varying degrees. Both can work together to lead to AD progression. How to define the interaction between the two in the occurrence and progression of disease is also the focus of clinical research on AD. In this context, the 2018 NIA-AA standard update pointed out that the AT(N) architecture can be extended according to the AD comorbidity. For example, if AD is complicated with cerebrovascular disease, AT (N) can be correspondingly extended to ATV (N). The international clinical research based on AT(N) is very limited, while the research on ATV (N) is blank at present.

At present, PET-CT or PET-MR can be used to perform aβ and Tau molecular imaging and FDG-PET can reflect the damage degree of neurons through the quantitative detection of brain glucose metabolism, and realize the early accurate individual diagnosis of AD based on AT(N) architecture. PET-MR can also realize the simultaneous evaluation of patients' vascular comorbidity. For example, the SVD load score of MRI images is often used in clinical evaluation. Therefore, PET-MR research is carried out on patients with AD-MCI, It can realize the early accurate identification and comprehensive evaluation of AD based on AT(V) N architecture, and help to explore the contribution of degenerative factors and vascular load to the occurrence and development of cognition. It is a hot spot in clinical research in the field of AD at present, and it is in urgent need of breakthrough. At present, the research on the central biomarkers of early clinical AD is very limited, especially the longitudinal study which is combination of Aβ、 Tau and FDG multimodal PET images.