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

¹ From the Gerontological Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore (LF, K-BY, E-HK, and T-PN); the Department of Psychological Medicine, National University of Singapore, Singapore (LF, E-HK, and T-PN); and the Department of Statistics and Applied Probability (JL) and the Department of Geriatric Medicine (K-BY), Alexandra Hospital, Singapore.

² Supported by a research grant (no. 03/1/21/17/214) from the Biomedical Research Council, Agency for Science, Technology and Research (ASTAR).

³ Reprints not available. Address correspondence to L Feng, Gerontological Research Programme, National University of Singapore, Department of Psychological Medicine, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074. E-mail: pcmfl{at}nus.edu.sg.

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 4. Hence, it is important to further examine this gene-nutrient interaction.

Objective: The aim was to investigate the role of apolipoprotein E (APOE) 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 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 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 4 carriers than in APOE 4 noncarriers (P for interaction = 0.016). Significant interactions between natural log-transformed vitamin B-12 and APOE 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 4 carriers but not in APOE 4 noncarriers.

Conclusion: The association between vitamin B-12 and cognitive function was moderated by APOE 4 status.