title: Association of cognitive impairment with combinations of vitamin B₁₂-related parameters.
abstract: 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.
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, DK-8000 Aarhus, Denmark. dolild@rm.dk
authors.forename: Dorte L
authors.initials: DL
authors.lastname: Lildballe
authors.forename: Sergey
authors.initials: S
authors.lastname: Fedosov
authors.forename: Paul
authors.initials: P
authors.lastname: Sherliker
authors.forename: Harold
authors.initials: H
authors.lastname: Hin
authors.forename: Robert
authors.initials: R
authors.lastname: Clarke
authors.forename: Ebba
authors.initials: E
authors.lastname: Nexo
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000378:metabolism* / Q000523:psychology*; D003430:Cross-Sectional Studies; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008764:Methylmalonic Acid / Q000097:blood; D018570:Risk Assessment; D014155:Transcobalamins / Q000032:analysis; D014805:Vitamin B 12 / Q000097:blood*; D014806:Vitamin B 12 Deficiency / Q000097:blood
chemical_list: D015415:Biomarkers; D014155:Transcobalamins; D006710:Homocysteine; D008764:Methylmalonic Acid; D014805:Vitamin B 12