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This Article Full Text (Publish Ahead of Print[PDF]) All Versions of this Article: 89/4/1263    most recent ajcn.2008.26969v1 Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Feng, L. Articles by Ng, T.-P. Search for Related Content PubMed PubMed Citation Articles by Feng, L. Articles by Ng, T.-P. Agricola Articles by Feng, L. Articles by Ng, T.-P.

Vitamin B-12, apolipoprotein E genotype, and cognitive performance in community-living older adults: evidence of a gene-micronutrient interaction^1,2,3

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.

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 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.

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

Received for publication September 12, 2008. Accepted for publication January 14, 2009.