Association of cognitive impairment with combinations of vitamin B₁₂-related parameters

Clin Chem. 2011 Oct;57(10):1436-43. doi: 10.1373/clinchem.2011.165944. Epub 2011 Aug 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Cognition Disorders / metabolism*
  • Cognition Disorders / psychology*
  • Cross-Sectional Studies
  • Homocysteine / blood
  • Humans
  • Methylmalonic Acid / blood
  • Risk Assessment
  • Transcobalamins / analysis
  • Vitamin B 12 / blood*
  • Vitamin B 12 Deficiency / blood


  • Biomarkers
  • Transcobalamins
  • Homocysteine
  • Methylmalonic Acid
  • Vitamin B 12