Relation of Cerebral Vessel Disease to Alzheimer’s Disease Dementia and Cognitive Function in Older Persons: A Cross-sectional Study

BACKGROUND: Few pathologic data are available on cerebral vessel disease, dementia, and cognition. This cross-sectional study examined associations of cerebral atherosclerosis and arteriolosclerosis neuropathology with probable and possible Alzheimer’s disease (AD) dementia and level of cognitive function, in a large group of older persons who came to autopsy. METHODS: 1,143 older women or men (median age-at-death = 88.8 years; 42% with AD dementia) underwent annual clinical evaluations and agreed to brain autopsy at time-of-death, as part of one of two cohort studies of aging. Neuropsychological data proximate-to-death were used to create summary measures of global cognition and cognitive domains. Data across all years were used to determine presence of the clinical syndrome of AD dementia. Systematic neuropathologic evaluations documented severity of cerebral large (atherosclerosis) and small vessel disease (arteriolosclerosis). Using regression analyses adjusted for demographics, gross and micro-infarcts and AD pathology, we examined associations of vessel disease severity with odds of probable and possible AD dementia and level of cognition. FINDINGS: Moderate-to-severe atherosclerosis was present in 445 (39%) subjects, and arteriolosclerosis in 401 (35%). The odds of AD dementia was higher with moderate-to-severe atherosclerosis (OR=1.33; 95%CI:1.11–1.58) and arteriolosclerosis (OR=1.20; 95%CI:1.04–1.40). Atherosclerosis was associated with lower scores for global cognition (estimate= −0.10, SE=0.04; p=0.00096) and four cognitive domains (episodic memory, semantic memory, perceptual speed and visuospatial abilities; all p<0.019) but not working memory (p=0.21). Arteriolosclerosis was associated with lower scores for global cognition (estimate= −0.10, SE=0.03; p=0.0015) and four domains (all p<0.046), and a borderline/non-significant association was noted for visuospatial abilities (p=0.052). Findings were unchanged in analyses controlling for APOEε4 and vascular risk factors. INTERPRETATION: Cerebral atherosclerosis and arteriolosclerosis each contribute to the odds of AD dementia by 20–30% per level increase in severity, and are associated with lower scores in most cognitive domains. Associations remain after taking into account AD and infarct pathologies, and vascular factors. Cerebral vessel pathology may be an under-recognized risk factor for AD dementia. FUNDING: United States National Institutes of Health.