Joint effect of the APOE gene and midlife systolic blood pressure on late-life cognitive impairment - The Honolulu-Asia aging study

Background and Purpose-The aim of this study, was to explore the joint effe ct of the APOE epsilon4 allele and midlife systolic blood pressure (SBP) on the risk for poor cognitive function in late life. Methods-The study includes 3605 surviving members of the cohort of the Japa nese-American men followed prospectively over 26 years (1965-1991) as a par t of the Honolulu Heart Program, In 1965 men were aged 45 to 68 years and w ere living in the island of Oahu, Hawaii. For this study the sample was div ided into 4 categories: normal SBP (< 160 mm Hg)/No epsilon4, as the refere nce category; normal SBP/epsilon4; high S betaP/no epsilon4 high SBP/epsilo n4. The relative risk (RR) of late-life intermediate and poor cognitive fun ction relative to good function was measured by the Cognitive Abilities Scr eening Instrument (CASI) test. Results-After adjusting for age, education, smoking, alcohol use, and body mass index, the RR for poor cognitive function (CASI < 74) compared with go od cognitive function (CASI > 82) in never-treated subjects, was 1.3 (95% C I 0.9 to 1.9) for the normal SBP/epsilon4 category, 2.6 (0.7 to 10.0) for t he high SBP/no epsilon4, and 13.0 (1.9 to 83.8) for the high SBP/epsilon4. Adjustment for diabetes, prevalent stroke. coronary disease, and ankle-brac hial index reduced the RR of poor cognition by 25.5% (RR 13.0 to 10.8) in t hose with both risk factors. In the treated group, the RR was 1.9 (0.7 to 4 .5) for those with both risk factors. Conclusions-The results suggest that midlife high SBP has a stronger advers e effect oil cognitive function in persons with higher genetic susceptibili ty, but this effect may be modified by antihypertensive treatment.