Cerebral Amyloid Angiopathy Pathology and Cognitive Domains in Older Persons

Objective: To examine the relation of cerebral amyloid angiopathy (CAA) to cognitive domains in older community-dwelling persons with and without dementia. Methods: Subjects were 404 persons in the Religious Orders Study, a cohort study of aging, who underwent annual clinical evaluations, including 19 neuropsychological tests from which 5 cognitive domain and global summary scores were derived, and brain autopsy at time-of-death (mean age-at-death 86). Using amyloid-beta immunostaining, CAA severity was graded in 5 regions (midfrontal, inferior temporal, angular, calcarine, and hippocampal cortices), as 0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe. Because severity was related across regions (all r(s) > 0.63), and almost all persons had some CAA, we averaged regional CAA scores and created class variable predictors for no-to-minimal (< 0.5), mild-to-moderate (0.5-2.5) and moderate-to-very severe CAA (> 2.5). Results: CAA was very common (84.9%; 94 had no-to-minimal, 233 mild-to-moderate, and 76 moderate-to-very severe disease) and was related to AD pathology (r(s) = 0.68). In linear regression analyses controlling for age, sex, education, AD pathology, infarcts, and Lewy bodies, moderate-to-very severe CAA was associated with lower perceptual speed (p = 0.012) and episodic memory (p = 0.047), but not semantic memory, working memory, visuospatial skills, or a composite of all cognitive measures. No associations of mild-to-moderate CAA with cognition were found. Dementia did not modify these findings. Interpretation: CAA pathology is very common in older community-dwelling persons and is associated with AD pathology. Moderate-to-very severe CAA, but not mild-to-moderate CAA, is associated with lower performance in specific cognitive domains, most notably perceptual speed, separately from the effect of AD pathology. ANN NEUROL 2011;69:320-327