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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 effect of the APOE &egr;4 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 Japanese-American men followed prospectively over 26 years (1965–1991) as a part of the Honolulu Heart Program. In 1965 men were aged 45 to 68 years and were living in the island of Oahu, Hawaii. For this study the sample was divided into 4 categories: normal SBP (<160 mm Hg)/No &egr;4, as the reference category; normal SBP/&egr;4; high SBP/no &egr;4; high SBP/&egr;4. The relative risk (RR) of late-life intermediate and poor cognitive function relative to good function was measured by the Cognitive Abilities Screening 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 good cognitive function (CASI ≥82) in never-treated subjects was 1.3 (95% CI 0.9 to 1.9) for the normal SBP/&egr;4 category, 2.6 (0.7 to 10.0) for the high SBP/no &egr;4, and 13.0 (1.9 to 83.8) for the high SBP/&egr;4. Adjustment for diabetes, prevalent stroke, coronary disease, and ankle-brachial index reduced the RR of poor cognition by 25.5% (RR 13.0 to 10.8) in those 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 adverse effect on cognitive function in persons with higher genetic susceptibility, but this effect may be modified by antihypertensive treatment.