Abstract
OBJECTIVE: We tested the hypothesis that cerebral amyloid angiopathy (CAA) is related to Alzheimer disease (AD) dementia and decline in multiple cognitive systems in old age, independent of AD plaque and tangle pathology and other common age-related neuropathologies. METHODS: Participants (n = 1,113) came from 2 longitudinal clinical-pathologic studies of aging, the Rush Memory and Aging Project and the Religious Orders Study. All underwent annual clinical evaluations including detailed cognitive testing for a mean of 7.1 years before death. Clinical diagnoses of AD were established after reviewing all clinical data, blinded to neuropathologic information. Neuropathologic examinations provided measures of CAA, AD pathology, macroscopic infarcts, microinfarcts, and neocortical Lewy bodies. The association of CAA with AD dementia was examined using logistic regression models, and its association with cognitive decline was examined using linear mixed models. RESULTS: CAA was common, present in 78.9% of participants, and moderately related to AD pathology (ρ = 0.401, p < 0.0001). In analyses adjusted for plaques, tangles, and other common age-related neuropathologies, CAA was associated with an increased odds of AD dementia (odds ratio = 1.237, 95% confidence interval 1.082-1.414) and an increased rate of decline in global cognition, perceptual speed, episodic memory, and semantic memory. The associations of CAA with cognitive outcomes were not driven by the presence of capillary involvement. CONCLUSIONS: CAA is an important determinant of AD dementia and decline in multiple cognitive systems in old age.