The effect of apolipoprotein E ε4 in the relationships of smoking and drinking to cognitive function

Objectives: To investigate the joint effect of the apolipoprotein E epsilon 4 (APOE epsilon 4), 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 epsilon 4 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 epsilon 4 indicated that the protective effect of light drinking was stronger and the harmful effect of smoking was weaker among APOE epsilon 4 carriers than among noncarriers. Conclusions: These data suggest a possible mediating effect of the APOE epsilon 4 allele in the relation of smoking and drinking to cognitive function in the elderly.