The effect of apolipoprotein E epsilon4 in the relationships of smoking and drinking to cognitive function

Neuroepidemiology. 1999;18(3):125-33. doi: 10.1159/000026204.


Objectives: To investigate the joint effect of the apolipoprotein E epsilon4 (APOE epsilon4), smoking and drinking on cognitive performance in a population-based longitudinal study of elderly men.

Design and setting: The NHLBI Twin Study, a longitudinal cardiovascular study of World War II, white, male veterans.

Participants: A total of 589 male participants in the third cardiovascular examination of this panel and aged 59-69 when assessed for cognitive function.

Outcome measures: Cognitive function assessed by the Mini-Mental State Examination, the Digit Symbol Substitution Test, the Benton Visual Retention Test, APOE epsilon4 allele frequency and cardiovascular disease (CVD) health status.

Results: For the sample as a whole, after adjustment for age, education and CVD, smoking was significantly associated with poor cognitive function (odds ratio (OR) = 2.0, 95% confidence interval (CI) 1.2-3.2, in current smokers compared with never smokers), whereas light drinking (one or fewer drinks per day) showed a protective effect (OR = 0.6, 95% CI 0.4-0.9 compared with abstainers). Stratification by APOE epsilon4 indicated that the protective effect of light drinking was stronger and the harmful effect of smoking was weaker among APOE epsilon4 carriers than among noncarriers.

Conclusions: These data suggest a possible mediating effect of the APOE epsilon4 allele in the relation of smoking and drinking to cognitive function in the elderly.

Publication types

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

MeSH terms

  • Aged
  • Alcohol Drinking / genetics*
  • Alleles
  • Apolipoproteins E / genetics*
  • Cerebrovascular Disorders / etiology
  • Cognition / physiology*
  • Follow-Up Studies
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Smoking / adverse effects
  • Smoking / genetics*
  • Twins / genetics
  • Veterans / psychology


  • Apolipoproteins E