Apolipoprotein E Genotypes and the Incidence of Alzheimer's Disease among Persons Aged 75 Years and Older: Variation by Use of Antihypertensive Medication?

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Abstract
The authors examined the impact of the apolipoprotein E (APOE)*ε4 allele on Alzheimer's disease incidence in relation to use of antihypertensive medication. A population-based (Kungsholmen Project) cohort of 985 nondemented Swedish subjects aged ≥75 years was followed for an average of 3 years (1990–1992); 164 dementia (122 Alzheimer's disease) cases were identified. Compared with *ε3/*ε3, the APOE *ε4 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 baseline (n = 432, 80% used diuretics) had a decreased risk of dementia (RR = 0.6, 95% CI: 0.5, 0.9) and Alzheimer's disease (RR = 0.5, 95% CI: 0.3, 0.8) after adjustment for several variables, including APOE. The effect of antihypertensive medication use was more pronounced among *ε4 carriers. For those 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 (95% 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 *ε4 allele is an important predictor of dementia and Alzheimer's disease incidence. Further studies are needed to clarify whether use of antihypertensive medication, especially diuretics, modifies the effect of the allele.