Apolipoprotein E, cardiovascular disease and cognitive function in aging women.

The apolipoprotein E (APOE) e4 allele increases risk of Alzheimer disease and cardiovascular diseases. We examined APOE genotypes alone or combined with cardiovascular conditions in relation to cognitive function in 4227 Nurses' Health Study participants, 70-80 years old. From 1995 to 2001, and again 2 years later, participants received telephone cognitive assessments of general cognition, category fluency, verbal memory and working memory. In biennial questionnaires since 1976, participants have provided extensive health information including cardiovascular conditions. Compared with women with the e3/3 genotype, e4 carriers performed worse at baseline across all tests (mean global composite score was lower by 0.10 points (95% confidence interval=-0.15, -0.05)) and declined more (mean change in global score was -0.07 points (95% CI=-0.12, -0.03)), with a strong allele dose-response trend (P-trend=0.0003). Among participants 75+ years, e2 carriers performed best. Women with an e4 allele and cardiovascular conditions such as transient ischemic attack or untreated hypertension had the worst cognition. Thus, APOE genotypes strongly influenced cognitive function and decline; prevention of cardiovascular disease may limit these effects.