Association of Cognitive Impairment with Combinations of Vitamin B12-Related Parameters

BACKGROUND: Low vitamin B-12 concentrations have been associated with higher risks of cognitive impairment, but whether these associations are causal is uncertain. The associations of cognitive impairment with combinations of vitamin B-12, holotranscobalamin, methylmalonic acid, and total homocysteine, and with the vitamin B-12 transport proteins transcobalamin and haptocorrin, have not been previously studied. METHODS: We performed a population- based cross-sectional study of 839 people 75 years old or older. We examined the association of cognitive function as measured by mini-mental state examination scores, with markers of vitamin B-12 status. Spearman correlations as well as multivariate-adjusted odds ratios and 95% CIs for cognitive impairment were calculated for extreme thirds of serum concentrations of vitamin B-12, holotranscobalamin, methylmalonic acid, total homocysteine, combination of these markers in a wellness score, heaptocorrin, and transcobalamin for all data and with B12 analogs in a nested case-control study. RESULTS: Cognitive impairment was significantly associated with low vitamin B-12 [ odds ratio 2.3 ( 95% CI 1.2-4.5)]; low holotranscobalamin [4.1 (2.0-8.7)], high methylmalonic acid [3.5 (1.8-7.1)], high homocysteine [4.8 (2.3-10.0)] and low wellness score [5.1 (2.61-10.46)]. After correction for relevant covariates, cognitive impairment remained significantly associated with high homocysteine [4.85 (2.24-10.53)] and with a low wellness score [5.60 (2.61-12.01)] but not with transcobalamin, haptocorrin, or analogs on haptocorrin. CONCLUSIONS: Cognitive impairment was associated with the combined effects of the 4 biomarkers of vitamin B-12 deficiency when included in a wellness score but was not associated with binding proteins or analogs on haptocorrin. (C) 2011 American Association for Clinical Chemistry