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Alzheimer’s disease is a neurodegenerative disorder and the most common cause of dementia, accounting for 60-80% of all dementia cases. Alzheimer’s disease typically presents with prominent amnestic cognitive impairment, but its clinical impact is modified by concomitant neurodegenerative and cerebrovascular conditions. The greatest known risk factor is increasing age; however, Alzheimer’s disease is not a normal part of aging and many modifiable and non-modifiable factors have been found to influence its development and progression. Pathologically, the disease is characterized by a prolonged preclinical phase, during which the abnormal accumulation of amyloid-β and tau proteins occurs in the brain decades before the initial clinical symptoms emerge. With the advent of amyloid-β and tauspecific positron emission tomography (PET) tracers, these pathologies can now be visualized in living individuals. Using multimodal imaging, it is therefore possible to investigate various brain pathologies across different developmental phases. This enables these pathologies to be studied in early disease stages, allowing investigation of their independent or interactive impact on cognition as well as potential risk and protective factors.

This dissertation combines multimodal imaging, genetic information, lifestyle factors, and clinical data to study Alzheimer’s disease in its earliest stages. More specifically, it investigates the relationships between the cardinal Alzheimer’s disease pathologies, namely aggregated amyloid-β and tau, and their connections to vascular pathologies, regional gray matter thickness/volume, and cognitive performance …