Supplementary Material for: Apolipoprotein E e4 and Cognitive Function: A Modifiable Association? Results from Two Independent Cohort Studies

<b><i>Background:</i></b> The apolipoprotein E <i>(APOE)</i> e4 genetic polymorphism is a major risk factor for Alzheimer' s disease, hence the possible prevention of its detrimental effects on cognition is of high relevance. <b><i>Methods:</i></b> We used linear regression models to assess associations of <i>APOE</i> e4 with cognitive performance in a population-based cohort study (n = 1,434) and in a cohort of patients with coronary heart disease (n = 366), and restricted cubic splines to explore dose-response relationships between serum cholesterol levels and cognition depending on <i>APOE</i> polymorphism. <b><i>Results:</i></b> The association of <i>APOE</i> e4 with cognitive function was strongly amplified in the presence of hypercholesterolemia and cardiovascular disease in both independent cohorts; hypercholesterolemia was associated with cognitive function only among <i>APOE</i> e4 carriers in the presence of cardiovascular disease. The interaction effect between <i>APOE</i> genotype and hypercholesterolemia was statistically significant in both cohorts. <b><i>Conclusions:</i></b> The detrimental effects of <i>APOE</i> e4 polymorphism on cognition may strongly depend on modifiable risk factors.