MIDLIFE CARDIOVASCULAR RISK-FACTORS, APOE, AND COGNITIVE DECLINE IN ELDERLY MALE TWINS

Objective: To investigate the combined effect of the apolipoprotein E epsilon 4 (ApoE4) allele and midlife cardiovascular risk factors on c ognitive decline. Methods: Data are from the National Heart, Lung, and Blood Institute Twin Study-a longitudinal cardiovascular epidemiologi c study of World War II male veteran twins currently in its 27th year of follow-up. Subjects were assessed for cardiovascular risk factors, including BP and glucose levels, at mean ages 48, 58, and 63 years. Pa rticipants in the current study are 410 individual twin subjects for w hom cognitive function was measured twice, at ages 63 and 73 years. Te n-year change scores in performance on neuropsychological test examina tions were adjusted for age, education, baseline score, and incident c ardiovascular disease. Results: For the sample as a whole, we observed a significant decline (p < 0.01) in cognitive performance over the 10 years of follow-up. ApoE4 carriers with midlife hyperglycemia experi enced the greatest decline in performance, which was also greater than expected from the separate effects combined. Midlife hypertension and ApoE4, were each associated with excess decline in performance on te sts of psychomotor speed. Their joint effect, however, was not greater than expected from the separate effects combined. Conclusions: ApoE4 and midlife cardiovascular risk factors may have a synergistic effect on decline in cognitive function. This effect may be due to greater v ascular or degenerative damage among subjects with ApoE4.