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Abstract

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. Ann Neurol 2007