Effect of infarcts on dementia in the Baltimore longitudinal study of aging

Abstract

Objective: To define the magnitude and mechanism of the effect of brain infarcts on the odds of dementia in a prospective study.

Methods: We examined the effects of brain infarcts and Alzheimer's disease (AD) pathology on the risk for dementia in 179 subjects from the Baltimore Longitudinal Study of Aging Autopsy Program. All subjects had longitudinal clinical and cognitive evaluations, and underwent postmortem examination of the brain.

Results: Brain infarcts were common in our cohort, and both symptomatic and asymptomatic infarcts conferred a significant increase in the odds of dementia. Risk factors for stroke in the absence of an infarct did not increase the odds of dementia, which was quantitatively related to the number but not the size of hemispheral infarcts; deep subcortical infarcts conferred no increased risk for dementia. The contribution of microscopic infarcts to dementia was significant and equivalent to that of macroscopic infarcts. In subjects with intermediate AD pathology scores, a single macroscopic hemispheral infarct was sufficient to cause dementia. A logistic regression model of the effect of infarcts and AD pathology on dementia indicated that AD pathology alone accounts for 50% of the dementia seen in this cohort, and that hemispheral infarcts alone or in conjunction with AD pathology account for 35%.

Interpretation: Cerebrovascular disease is a significant and potentially preventable cause of dementia in the Baltimore Longitudinal Study of Aging. Burden and location of infarcts are significantly associated with cognitive decline.

Fig 1

Effect of the number of infarcts on the odds of dementia. (A) The relation between the number of macroscopic infarcts and dementia is shown stratified by location. The listed odds ratio (O.R.) refers to the age- and sex-adjusted odds for a single-step increase in the number of relevant infarcts. (B) The same analysis is applied to microscopic infarcts. All data are plotted as standard error plots.

Fig 2

Interaction between cerebrovascular disease and Alzheimer’s disease (AD) pathology in the cause of dementia. (A) Standard error plots of the dementia rate in subjects with increasing amounts of composite AD pathology are shown, stratified by the presence or absence of any infarct. Asterisks indicate significant differences between the infarct and no infarct groups. (B) Standard error plots of the dementia rate in subjects with increasing numbers of macroscopic hemispheral infarcts are shown, stratified by the amount of composite AD pathology. The indicated p values compare the composite AD pathology score 4 group with the composite AD pathology 2/3 group at the indicated number of hemispheral macroscopic infarcts. (C) The number of macroscopic hemispheral infarcts in demented and nondemented subjects at the indicated amount of composite AD pathology is shown. *p = 0.02 compared with the demented group with an AD pathology score of 2 or 3.