Vitamin B-12, apolipoprotein E genotype, and cognitive performance in community-living older adults: evidence of a gene-micronutrient interaction

Background: The relation between vitamin B-12 and cognitive function in older adults is unclear. Limited evidence suggests that the relation is modulated by apolipoprotein E epsilon 4. Hence, it is important to further examine this gene-nutrient interaction. Objective: The aim was to investigate the role of apolipoprotein E (APOE) epsilon 4 as a genetic predisposing factor modulating the effect of vitamin B-12 on cognitive function. Design: A battery of neuropsychological tests, including the Mini-Mental State Examination (MMSE) for global cognition, was administered at the baseline assessment to 539 Chinese adults aged >= 55 y. The MMSE was repeated at a median 18 mo (n = 376) and a median of 38 mo (n 247) after baseline. The interaction of vitamin B-12 and APOE epsilon 4 on cognitive function was examined in a linear mixed-effects model for MMSE and in a multiple linear regression model for neuropsychological test scores. Results: APOE epsilon 4 was associated with a lower MMSE score. Vitamin B-12 (natural log transformed) was positively related to MMSE score, and this association was much stronger in APOE epsilon 4 carriers than in APOE epsilon 4 noncarriers (P for interaction = 0.016). Significant interactions between natural log-transformed vitamin B-12 and APOE epsilon 4 were also found for the Digit Span Backward Longest Sequence (P for interaction = 0.013) and Rey Auditory Verbal Learning Test immediate recall (P for interaction = 0.005). Better performance in these 2 tests was associated with vitamin B-12 in APOE epsilon 4 carriers but not in APOE epsilon 4 noncarriers. Conclusion: The association between vitamin B-12 and cognitive function was moderated by APOE epsilon 4 status. Am J Clin Nutr 2009; 89: 1263-8.