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Neurology 1999;53:321
© 1999 American Academy of Neurology
Articles

APOE-{epsilon}4 count predicts age when prevalence of AD increases, then declines

The Cache County Study

J. C. S. Breitner, MD, MPH, B. W. Wyse, PhD, J. C. Anthony, PhD, K. A. Welsh-Bohmer, PhD, D. C. Steffens, MD, M. C. Norton, MS, J. T. Tschanz, PhD, B. L. Plassman, PhD, M. R. Meyer, PhD, I. Skoog, MD and A. Khachaturian, BS

From the Department of Mental Hygiene (Drs. Breitner, Anthony, and Meyer, and A. Khachaturian), The Johns Hopkins University, Baltimore, MD; the Department of Psychiatry and Behavioral Sciences and the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Drs. Breitner, Steffens, Plassman, and Welsh-Bohmer), Duke University, Durham, NC; the College of Family Life (Drs. Wyse and Tschanz, and M.C. Norton), Utah State University, Logan, UT; and the Institute of Clinical Neuroscience and Department of Psychiatry (Dr. Skoog), Gothenberg University, Gothenberg, Sweden.

Address correspondence and reprint requests to Dr. John C.S. Breitner, The Johns Hopkins University, Room 850 Hampton House, 624 No. Broadway, Baltimore, MD 21205.

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 APOE 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 participation rates.

METHODS: We screened for dementia with a brief cognitive test and structured telephone Dementia Questionnaire, then examined all individuals with apparent cognitive symptoms and a sample of others. We estimated age-specific prevalence of AD and other dementias and used multiple logistic 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 value versus autopsy confirmation 85%). The adjusted prevalence estimate for AD was 6.5% and for all dementias 9.6%. After age 90, the adjusted prevalence estimate for AD was 28% and for all dementias 38%. Regression models showed strong variation in AD prevalence with age, sex, education, and number of {epsilon}4 alleles (effect of {epsilon}2 not significant). Models were improved 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 association of AD with female sex was ascribable entirely to individuals with {epsilon}4.

CONCLUSIONS: In participants with no {epsilon}4 alleles, the age-specific prevalence of AD reached a maximum and then declined after age 95. 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 those with {epsilon}4. The {epsilon}4 allele accounted for 70% of the population attributable risk for AD.




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