Apolipoprotein E ε4 Allele, Elevated Midlife Total Cholesterol Level, and High Midlife Systolic Blood Pressure Are Independent Risk Factors for Late-Life Alzheimer Disease

Abstract

BACKGROUND: Presence of the apolipoprotein E (apoE) epsilon4 allele, which is involved in cholesterol metabolism, is the most important genetic risk factor for Alzheimer disease. Elevated midlife values for total cholesterol level and blood pressure have been implicated recently as risk factors for Alzheimer disease. OBJECTIVE: To study the relative importance and the putative relationship among the apoE epsilon4 allele, midlife total cholesterol level, and midlife blood pressure as risk factors for late-life Alzheimer disease. DESIGN: Prospective population-based study. SETTING: Kuopio and Joensuu, eastern Finland. PARTICIPANTS: Participants were derived from random population surveys from 1972, 1977, 1982, and 1987. A total of 1449 persons (73%), 65 to 79 years of age, participated in the reexamination in 1998 (mean follow-up, 21 years). MEASUREMENTS: Midlife blood pressure and total cholesterol level, apoE genotype, and development of Alzheimer disease during follow-up. RESULTS: The apoE epsilon4 allele was an independent risk factor for Alzheimer disease, even after adjustment for midlife vascular risk factors and other confounders (odds ratio, 2.1 [95% CI, 1.1 to 4.1]). Similarly, elevated midlife values for serum total cholesterol level (odds ratio, 2.8 [CI, 1.2 to 6.7]) and systolic blood pressure (odds ratio, 2.6 [CI, 1.1 to 6.6]) were independent risk factors for Alzheimer disease, even after adjustment for apoE genotype and other confounding factors. CONCLUSIONS: The association between the apoE epsilon4 allele and Alzheimer disease does not seem to be mediated by vascular factors. The apoE epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for Alzheimer disease. The risk for Alzheimer disease from treatable factors--elevated total cholesterol level and blood pressure--appears to be greater than that from the apoE epsilon4 allele.