Abstract

OBJECTIVE: To investigate whether impaired cognitive function is an early manifestation of vascular injury in the brain and therefore predicts risk of subsequent cardiovascular disease. METHODS: The study population consisted of 12,096 middle-aged participants in the Atherosclerosis Risk in Communities (ARIC) Study who had no history of stroke or coronary heart disease (CHD) at the time of cognitive testing. Cognitive function was measured using the Digit-Symbol Substitution Test (DSST), the Word Fluency Test, and the Delayed Word Recall Test. Cognitive test scores were adjusted for demographic factors and then evaluated as predictors of incident cardiovascular events using Cox proportional hazards analysis. RESULTS: Over a median follow-up period of 6.4 years, there were 516 incident cardiovascular events (292 myocardial infarctions, 50 CHD deaths, and 174 strokes), resulting in an average annual incidence rate of 0.7%. Lower adjusted scores on each cognitive test predicted a greater risk of incident cardiovascular events after controlling for established vascular risk factors (highest vs lowest quartile DSST, adjusted hazard ratio 1.56, 95% CI 1.23 to 1.97, p for linear trend by quartile < 0.001). The magnitude of the association was comparable with other commonly used predictors of vascular risk such as left ventricular hypertrophy on EKG and high-density lipoprotein cholesterol level of <35 mg/dL. CONCLUSION: Cognitive test scores below demographic norms predict incident cardiovascular disease in middle-aged subjects independently of established vascular risk factors.