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

From the Aging Research Center, Division of Geriatric Epidemiology and Medicine, Department of Neurotec, Karolinska Institutet and the Stockholm Gerontology Research Center, Stockholm, Sweden.

Address correspondence and reprint requests to Dr. Chengxuan Qiu, Stockholm Gerontology Research Center, Box 6401, Olivecronas väg 4, SE-113 82 Stockholm, Sweden; e-mail: chengxuan.qiu{at}neurotec.ki.se

Objective: To study the hypotheses that APOE-4 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-4 allele, high systolic pressure (140 mm Hg), and low diastolic pressure (<70 mm Hg) were associated with an increased risk of AD. APOE-4 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-4 status and counteracted the combined risk effect of the 4 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-4 allele.

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