title: APOE-epsilon4 count predicts age when prevalence of AD increases, then declines: the Cache County Study.
abstract: 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-epsilon4 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 epsilon4 alleles (effect of epsilon2 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 epsilon4 alleles. An association of AD with female sex was ascribable entirely to individuals with epsilon4.
  
  
  CONCLUSIONS
  In participants with no epsilon4 alleles, the age-specific prevalence of AD reached a maximum and then declined after age 95. In epsilon4 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 epsilon4. The epsilon4 allele accounted for 70% of the population attributable risk for AD.
authors.affiliation: Department of Mental Hygiene, The Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Breitner
authors.forename: B W
authors.initials: BW
authors.lastname: Wyse
authors.forename: J C
authors.initials: JC
authors.lastname: Anthony
authors.forename: K A
authors.initials: KA
authors.lastname: Welsh-Bohmer
authors.forename: D C
authors.initials: DC
authors.lastname: Steffens
authors.forename: M C
authors.initials: MC
authors.lastname: Norton
authors.forename: J T
authors.initials: JT
authors.lastname: Tschanz
authors.forename: B L
authors.initials: BL
authors.lastname: Plassman
authors.forename: M R
authors.initials: MR
authors.lastname: Meyer
authors.forename: I
authors.initials: I
authors.lastname: Skoog
authors.forename: A
authors.initials: A
authors.lastname: Khachaturian
mesh_terms: D017677:Age Distribution; D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000032:analysis* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008403:Mass Screening; D011237:Predictive Value of Tests; D015995:Prevalence; D012307:Risk Factors; D017678:Sex Distribution; D011795:Surveys and Questionnaires
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E