Zhao JH, Brunner EJ, Kumari M, Singh-Manoux A, Hawe E, Talmud PJ, Marmot MG, Humphries SE. APOE polymorphism, socioeconomic status and cognitive function in mid-life--the Whitehall II longitudinal study. Soc Psychiatry Psychiatr Epidemiol. 2005;40(7):557-63.

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-epsilon4 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-epsilon4 genotypes.CONCLUSIONS: APOE-epsilon4 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.

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