Central to the quest of the etiology of Alzheimer’s disease is insight into how the two prevailing pathways, amyloid pathology and vascular pathology, influence disease development in its earliest stage. Previous studies have focused on these pathways separately, yet there is a void of studies that use an integrated approach to study both pathways simultaneously, in particular in a preclinical setting. This proposal will make use of the existing infrastructure within The Rotterdam Study, a large on-going population-based study with extensive multiple time-point imaging data, enabling detailed assessment of vascular pathology. In a sample of 700 subjects from this cohort with varying degrees of vascular pathology, we will acquire brain amyloid PET, and will assess how (progression of) vascular brain pathology relates to amyloid pathology. Furthermore, we will study how amyloid and vascular pathologies interact in their association with cognitive function and cognitive decline over time.
An increased understanding of the link between vascular pathology and amyloid pathology at the earliest stage of the disease would have implications for primary prevention, and risk stratification of individuals for future therapeutic trials.