Subclinical atherosclerosis is weakly associated with lower cognitive function in healthy hyperhomocysteinemic adults without clinical cardiovascular disease

Abstract
Objective Atherosclerosis is the most common pathologic process underlying cardiovascular disease (CVD). It is not well known whether subclinical atherosclerosis is an independent risk factor for lower cognitive function among individuals without clinically evident CVD. Methods We examined cross‐sectional associations between subclinical atherosclerosis and cognitive function in a community‐based sample of otherwise healthy adults with plasma homocysteine ≥8.5 µmol/L enrolled in the BVAIT study (n = 504, mean age 61 years). Carotid artery intima‐media thickness (CIMT), coronary artery calcium (CAC) and abdominal aortic calcium (AAC) were used to measure subclinical atherosclerosis. Cognitive function was assessed with a battery of neuropsychological tests. A principal components analysis was used to extract five uncorrelated cognitive factors from scores on individual tests, and a measure of global cognition was derived. Multivariable linear regression was used to examine the association between subclinical atherosclerosis and cognitive function, adjusting for other correlates of cognition. Results Increasing thickness of CIMT was associated with significantly lower scores on the verbal learning factor (β = −0.07 per 0.1 mm increase CIMT [SE(β ) = 0.03], p = 0.01). CAC and AAC were not individually associated with any of the cognitive factors. Conclusions This study provides evidence that increasing CIMT is weakly associated with lower verbal learning abilities but not global cognition in a population of otherwise healthy middle‐to‐older aged adults with elevated plasma homocysteine levels but without clinically evident CVD. The association between CIMT and poor verbal learning may pertain particularly to men. Copyright © 2008 John Wiley & Sons, Ltd.