Subcortical infarcts, Alzheimer's disease pathology, and memory function in older persons

Objective: Examine the effects of subcortical infarcts with Alzheimer's disease (AD) pathology on dementia, episodic memory, and other cognitive abilities in older persons. Methods: Participants included 148 autopsied subjects of the Rush Memory and Aging Project (mean age, 88.0 years), a longitudinal clinicopathological study. Cognition was assessed yearly with 21 neuropsychological tests. Infarcts were visualized on coronal slabs, and plaques and neurofibrillary tangles were counted and standardized to form a composite measure of AD pathology. Multiple regression analyses were used controlling for age, sex, and education. Results: Fifty-three (35.8%) subjects had cerebral infarcts. After accounting for AD pathology, infarcts increased the odds of dementia by 5.1-fold (95% confidence interval, 1.98-12.92) and lowered cognitive function by 0.50 standard unit (p = 0.001). After controlling for cortical infarcts and AD pathology, subcortical infarcts, present in 39 of 53 (73.6%) subjects with infarcts, increased the odds of dementia by almost 4-fold and reduced cognitive function by more than a third of a unit (parameter estimate = -0.37; p = 0.03). In analyses with cognitive abilities, subcortical infarcts were associated with lower episodic, semantic, and working memory (p <= 0.05), and had an interaction with AD pathology to further worsen working memory (p = 0.02). Interpretation: Subcortical infarcts add to deleterious effects of AD pathology by increasing the odds of dementia and lowering memory function.