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

Abstract

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 ε4. Hence, it is important to further examine this gene-nutrient interaction. Objective: The aim was to investigate the role of apolipoprotein E (APOE) ε4 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 ε4 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 ε4 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 ε4 carriers than in APOE ε4 noncarriers (P for interaction - 0.016). Significant interactions between natural log-transformed vitamin B-12 and APOE ε4 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 ε4 carriers but not in APOE ε4 noncarriers. Conclusion: The association between vitamin B-12 and cognitive function was moderated by APOE ε4 status. © 2009 American Society for Nutrition.