Education modifies the effect of apolipoprotein epsilon 4 on cognitive decline

Neurobiol Aging. 2005 Jan;26(1):17-24. doi: 10.1016/j.neurobiolaging.2004.03.005.


Objectives: To assess the influence of education on the association between apolipoprotein E and cognitive change.

Design: Prospective cohort.

Participants: HMO-based sample of 2168 non-demented community-dwelling elderly followed over 6 years.

Measurements: Generalized estimating equations were used with the difference between baseline and follow-up cognitive abilities screening instrument (CASI) as the outcome variable.

Results: At follow-up, 6% of the sample had a decline of 1.5 S.D. or greater on the CASI. Compared to individuals without an APOE4 allele, individuals with a single APOE4 allele did not have greater CASI decline. By contrast, individuals with two APOE4 alleles experienced greater decline in cognitive performance and the magnitude of that decline decreased as years of educational attainment increased. These relationships held after adjusting for age, gender, ethnicity, depression, diabetes, and history of vascular disease.

Conclusion: Lower education was associated with steep 4-year cognitive decline for APOE4 homozygotes but not for APOE4 heterozygotes. Potentially modifiable host factors such as education could influence the association of high-risk genotypes and cognitive decline.

Publication types

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

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Apolipoprotein E4
  • Apolipoproteins E / physiology*
  • Cognition Disorders / epidemiology*
  • Cognition Disorders / genetics*
  • Educational Status*
  • Female
  • Follow-Up Studies
  • Health Maintenance Organizations / statistics & numerical data
  • Humans
  • Male
  • Neuropsychological Tests / statistics & numerical data
  • Prospective Studies
  • Retrospective Studies
  • Risk Factors


  • Apolipoprotein E4
  • Apolipoproteins E