APOE-epsilon 4 count predicts age when prevalence of AD increases, then declines - The Cache County Study

Objective: To examine the prevalence of Alzheimer's disease (AD) and other dementias in relation to age, education, sex, and genotype at APOE. Recent studies suggest age heterogeneity in the risk of AD associated with the APO E genotype and a possible interaction between APOE-epsilon 4 and female sex as risk factors. We studied these topics in the 5,677 elderly residents of Cache County, Utah, a population known for long life expectancy and high p articipation rates. Methods: We screened for dementia with a brief cognitiv e test and structured telephone Dementia Questionnaire, then examined all i ndividuals with apparent cognitive symptoms and a sample of others. We esti mated age-specific prevalence of AD and other dementias and used multiple l ogistic regression models to describe relation of AD prevalence to age, sex , education, and APOE genotype. Results: We found 335 demented individuals, 230 (69%) with definite, probable, or possible AD (positive predictive val ue versus autopsy confirmation 85%). The adjusted prevalence estimate for A D was 6.5% and for all dementias 9.6%. After age 90, the adjusted prevalenc e estimate for AD was 28% and for all dementias 38%. Regression models show ed strong variation in AD prevalence with age, sex, education, and number o f epsilon 4 alleles (effect of epsilon 2 not significant). Models were impr oved by a term for age-squared (negative coefficient) and by separate terms for interaction of age with presence of one or two epsilon 4 alleles. An a ssociation of AD with female sex was ascribable entirely to individuals wit h epsilon 4. Conclusions: In participants with no epsilon 4 alleles, the ag e-specific prevalence of AD reached a maximum and then declined after age 9 5. In epsilon 4 heterozygotes a similar maximum was noted earlier at age 87 , in homozygotes at age 73. Female sex was a risk factor for AD only in tho se with epsilon 4. The epsilon 4 allele accounted for 70% of the population attributable risk for AD.