Apolipoprotein E epsilon 4 affects new learning in cognitively normal individuals at risk for Alzheimer's disease

Neurobiol Aging. 2003 Nov;24(7):947-52. doi: 10.1016/s0197-4580(03)00006-x.


The Apolipoprotein E (APOE) epsilon 4 allele is an important risk factor for Alzheimer's disease (AD). Given the interest in early identification of at-risk individuals, we examined memory decline as a function of APOE status and age in cognitively intact participants aged 48-77 years old (yo). Participants were grouped by age (<60 versus > or =60) and APOE (epsilon4+/-). Longitudinal analysis of several components of memory over a 2-year interval showed a significant Age-by-APOE interaction reflecting a decline in new learning for the > or =60 epsilon4+ group only. Among epsilon4+, 76% of the > or =60 participants showed a decline versus 32% of the <60, but the amount of decline in new learning over the 2-year interval within the > or =60 group was not further influenced by age. That is, the size of the 2-year change was the same for 60 and 70 year old participants. This suggests that longitudinal study of new learning is a sensitive measure for detecting early cognitive changes in at-risk individuals that precede the symptomatic onset of mild cognitive impairment and AD.

Publication types

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

MeSH terms

  • Aged
  • Aging / physiology*
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / genetics*
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Female
  • Gene Frequency*
  • Genetic Predisposition to Disease
  • Humans
  • Longitudinal Studies
  • Male
  • Memory / physiology
  • Middle Aged
  • Risk Factors
  • Verbal Learning / physiology*


  • Apolipoprotein E4
  • Apolipoproteins E