Apolipoprotein E and cognitive change in an elderly population

Ann Neurol. 1996 Jul;40(1):55-66. doi: 10.1002/ana.410400111.


The apolipoprotein E (apoE) epsilon 4 allele is overrepresented, and the apoE epsilon 2 allele underrepresented, in Alzheimer's disease. To assess the risk of cognitive impairment in individuals with these genotypes in the general population, we studied a population-based sample of 1,899 individuals 65 years and older as a follow-up to the Iowa 65+ Rural Health Study. Multiple regression and logistic regression analyses demonstrated significant effects of apoE epsilon 4 and apoE epsilon 2 in predicting performance on a delayed recall task over a 4- to 7-year period. The magnitude of this effect was, however, fairly modest, with odds ratios for developing impairment of approximately 1.37 (95% confidence interval: 1.007, 1.850; p = 0.045) for apoE epsilon 4 and 0.53 (95% confidence interval: 0.368, 0.777; p = 0.001) for apoE epsilon 2. These effects were more pronounced in women than men. Importantly, 85% of elderly apoE E4/4 individuals (average age, 81) scored in the unimpaired range on a screening mental status test. Thus, many individuals reach old age without cognitive impair- ment despite inheritance of one or two apoE epsilon 4 alleles. This suggests that apoE genotyping will have limited utility as a diagnostic or prognostic indicator of cognitive decline in individuals.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged*
  • Alleles
  • Alzheimer Disease / complications
  • Alzheimer Disease / physiopathology
  • Apolipoproteins E / blood
  • Apolipoproteins E / genetics*
  • Brain / physiopathology
  • Cholesterol, HDL / blood
  • Cognition Disorders / complications
  • Cognition Disorders / diagnosis*
  • Cognition Disorders / physiopathology
  • Cross-Sectional Studies
  • Female
  • Genotype
  • Humans
  • Longitudinal Studies
  • Male
  • Polymerase Chain Reaction
  • Prospective Studies


  • Apolipoproteins E
  • Cholesterol, HDL