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

BACKGROUND: Low vitamin B12 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 B12, holotranscobalamin, methylmalonic acid, and total homocysteine, and with the vitamin B12 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 B12 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 B12, 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 B12 [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 B12 deficiency when included in a wellness score but was not associated with binding proteins or analogs on haptocorrin.