title: The association of APOE genotype and cognitive decline in interaction with risk factors in a 65-69 year old community sample.
abstract: BACKGROUND
  While the evidence of an association between the apolipoprotein E (APOE) *E4 allele and Alzheimer's disease is very strong, the effect of the *E4 allele on cognitive decline in the general population is more equivocal. A cross-sectional study on the lifespan effects of the *E4 allele 1 failed to find any effect of the *E4 allele on cognitive performance at ages 20-24, 40-44 or 60-64 years.
  
  
  METHODS
  In this four year follow-up study, we reexamine the effect of *E4 in the sample of 2,021 individuals, now aged 65-69 years.
  
  
  RESULTS
  Performance on the Mini-Mental State Examination (MMSE) was significantly poorer for *E4 homozygotes than heterozygotes or non-carriers. The effects of the *E4 genotype on cognitive decline over four years were found on the MMSE and Symbol-Digit Modalities test but only when controlling for risk factors such as head injury and education. Analyses were repeated with the exclusion of participants diagnosed with a mild cognitive disorder, with little change.
  
  
  CONCLUSIONS
  It is possible that *E4 carriers become vulnerable to greater cognitive decline in the presence of other risk factors at 65-69 years of age.
authors.affiliation: The Australian National University, Canberra, Australia. helen.christensen@anu.edu.au
authors.forename: Helen
authors.initials: H
authors.lastname: Christensen
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Batterham
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mackinnon
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Jorm
authors.forename: Holly A
authors.initials: HA
authors.lastname: Mack
authors.forename: Karen A
authors.initials: KA
authors.lastname: Mather
authors.forename: Kaarin J
authors.initials: KJ
authors.lastname: Anstey
authors.forename: Perminder S
authors.initials: PS
authors.lastname: Sachdev
authors.forename: Simon
authors.initials: S
authors.lastname: Easteal
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D001315:Australia; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D015577:Geriatric Assessment / Q000379:methods*; D006579:Heterozygote; D006801:Humans; D007361:Intelligence Tests; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D001057:Apolipoproteins E