Apolipoprotein E genotypes and the incidence of Alzheimer's disease among persons aged 75 years and older: Variation by use of antihypertensive medication?

The authors examined the impact of the apolipoprotein E (APOE)*epsilon4 all ele on Alzheimer's disease incidence in relation to use of antihypertensive medication. A population-based (Kungsholmen Project) cohort of 985 nondeme nted Swedish subjects aged greater than or equal to 75 years was followed f or an average of 3 years (1990-1992); 164 dementia (122 Alzheimer's disease ) cases were identified. Compared with *epsilon3/*epsilon3, the APOE*epsilo n4 allele increased the risk of developing dementia (relative risk (RR) = 1 .5, 95% confidence interval (CI):1.1, 2.1) and Alzheimer's disease (RR = 1. 7, 95% CI: 1.2, 2.5). Subjects using antihypertensive medication at baselin e (n = 432, 80% used diuretics) had a decreased risk of dementia (RR = 0.6, 95% Cl: 0.5, 0.9) and Alzheimer's disease (RR = 0.5, 95% CI: 0.3, 0.8) aft er adjustment for several variables, including APOE. The effect of antihype rtensive medication use was more pronounced among *epsilon4 carriers. For t hose not using antihypertensive medication, the relative risks of dementia and Alzheimer's disease for carriers were 2.2 (95% CI: 1.4, 3.4) and 2.3 (9 5% CI: 1.4, 3.7), respectively. The corresponding relative risks for those using antihypertensive medication were 0.9 (95% CI: 0.5, 1.6) and 1.1 (95% CI: 0.6, 2.2). The APOE*epsilon4 allele is an important predictor of dement ia and Alzheimer's disease incidence. Further studies are needed to clarify whether use of antihypertensive medication, especially diuretics, modifies the effect of the allele.