Biologically Active Vitamin B12, Homocysteine, and Alzheimer Disease

Baseline serum levels of homocysteine correlated positively and holotranscobalamin levels correlated negatively with AD risk in a population-based, 7-year cohort study.

Studies of the associations among the components of the vitamin B12 cascade and dementia have had inconsistent results (Eur J Neurol 2009; 16:808, Am J Clin Nutr 2007; 85:511, and Neurology 2004; 62:1972). In this study, researchers examined three of the cascade components — homocysteine, holotranscobalamin (holoTC, the biologically active fraction of vitamin B12), and folate — and subsequent risk for Alzheimer disease (AD). Participants were 271 initially nondemented older adults (baseline age range, 65–79) selected from a larger cohort based on the availability of baseline serum samples of these components. After a mean follow-up of 7.4 years, participants underwent a multistep AD screening process.

In a multiple logistic regression model adjusted for known cerebrovascular risk factors (including history of stroke, blood pressure, body-mass index, and smoking) and AD risk factors (including age, education, APOE 4, and Mini-Mental State Exam score), the odds ratios for AD were 1.16 per increase of 1 µmol/L of Hcy and 0.980 per increase of 1 pmol/L of holoTC. Of note, 95% confidence intervals for both calculations did not include 1. The authors report an attenuated link between Hcy and AD when adjusting for holoTC; however, the reported 95% confidence interval for this association included 1 (0.96–1.25). Folate levels were not associated with AD. The authors conclude that further study is needed, in light of the established associations of elevated Hcy with vascular disease and of vitamin B12 deficiency with neurological illness.

Comment: The authors acknowledge the obvious limitations of the study (e.g., the small sample size and one-time Hcy and holoTC measurements). A more universal challenge arises in determining the most sensitive marker of vitamin B12 deficiency (e.g., total serum vitamin B12, holoTC, or methylmalonic acid) and the true range of normal values. Nonetheless, these findings are provocative and suggest that simple supplementation with vitamin B12 in an aging population might be beneficial.

— Brandy R. Matthews, MD

Published in Journal Watch Neurology November 9, 2010

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