Combined effects of APOE genotype, blood pressure, and antihypertensive drug use on incident AD

Objective: To study the hypotheses that APOE-epsilon4 allele may interact with blood pressure to affect Alzheimer's disease (AD) occurrence and that antihypertensive therapy could modify such an effect. Methods: A dementia-free cohort of 966 community-dwelling persons aged 75 years and older in Stockholm, Sweden was followed to detect patients with AD using the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) diagnostic criteria. Data were analyzed using Cox proportional hazards models with adjustment for several potential confounders. Results: During a 6-year follow-up period, AD was diagnosed in 204 persons. APOE-epsilon4 allele, high systolic pressure (greater than or equal to140 mm Hg), and low diastolic pressure (<70 mm Hg) were associated with an increased risk of AD. APOE-ε4 allele combined with low diastolic pressure greatly increased the risk of AD independent of antihypertensive drug use. Antihypertensive therapy significantly reduced the risk of AD regardless of APOE-ε4 status and counteracted the combined risk effect of the ε4 allele with high systolic pressure on the disease. Conclusions: Elderly people with genetic susceptibility for Alzheimer's disease may experience a further increased disease risk if they have either high systolic pressure or low diastolic pressure. Antihypertensive therapy decreases the risk of Alzheimer's disease exerted by the APOE-ε4 allele.