APOE polymorphism, socioeconomic status and cognitive function in mid-life -: The Whitehall II Longitudinal Study

Objective The aim of this study was to investigate the association of the common apolipoprotein E gene (APOE) variants with cognitive function and cognitive decline in adult mid-life and explore the possibility that APOE genotype mediates the link between socioeconomic status (SES) and cognitive function. Methods Data on cognitive function, as measured by five cognitive tests, together with APOE genotype were obtained in an occupational cohort (the Whitehall II study) of 6,004 participants aged 44-69 years (1997-1999). Cognitive change was examined in 2,717 participants who had cognitive function measured at baseline (1991-1993). Results SES based on civil service employment grade was strongly related to cognitive function. There was no association between APOE genotype and employment grade. In women, participants with APOE-epsilon 4 had a lower memory score (p < 0.05), but the result was sensitive to data from a small number of individuals. A marginal cross-sectional difference in the semantic fluency score was found (p=0.07), and there was a relative decline at follow-up (p < 0.001, net change=-1.19; 95% CI, -1.90 to -0.49) in those with APOE-epsilon 4 genotypes. Conclusions APOE-epsilon 4 has little influence on cognitive decline in mid-life, whereas SES is a strong determinant, although APOE genotype may emerge as an important factor in cognitive function in later life.