title: Low vitamin B-12 status and risk of cognitive decline in older adults.
abstract: BACKGROUND
  Elevated total homocysteine (tHcy) concentrations have been associated with cognitive impairment, but it is unclear whether low vitamin B-12 or folate status is responsible for cognitive decline.
  
  
  OBJECTIVE
  We examined the associations of cognitive decline with vitamin B-12 and folate status in a longitudinal cohort study performed from 1993 to 2003 in Oxford, United Kingdom.
  
  
  METHODS
  Cognitive function was assessed with the Mini-Mental State Examination on >/=3 occasions during 10 y and related to serum concentrations of vitamin B-12, holotranscobalamin (holoTC), tHcy, methylmalonic acid (MMA), and folate with the use of linear mixed models in 1648 participants who provided blood in 1995.
  
  
  RESULTS
  Cognitive function declined abruptly at younger ages in some participants but remained intact in others until very old age. In multivariate regression analyses after adjustment for established risk factors, concentrations of holoTC (a marker of reduced vitamin B-12 status), tHcy, and MMA predicted cognitive decline, but folate did not. A doubling in holoTC concentrations (from 50 to 100 pmol/L) was associated with a 30% slower rate of cognitive decline (-0.137 to -0.083), whereas a doubling in tHcy (from 10 to 20 micromol/L) or MMA (from 0.25 to 0.50 micromol/L) was associated with >50% more rapid cognitive decline (-0.090 to -0.169) and (-0.104 to -0.169), respectively. After adjustment for all vitamin markers simultaneously, the associations of cognitive decline with holoTC and MMA remained significant.
  
  
  CONCLUSIONS
  Low vitamin B-12 status was associated with more rapid cognitive decline. Randomized trials are required to determine the relevance of vitamin B-12 supplementation for prevention of dementia.
authors.affiliation: Clinical Trial Service Unit, University of Oxford,, University of Oxford, Oxford, United Kingdom. robert.clarke@ctsu.ox.ac.uk
authors.forename: Robert
authors.initials: R
authors.lastname: Clarke
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Birks
authors.forename: Ebba
authors.initials: E
authors.lastname: Nexo
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
authors.forename: Joern
authors.initials: J
authors.lastname: Schneede
authors.forename: John
authors.initials: J
authors.lastname: Scott
authors.forename: Anne
authors.initials: A
authors.lastname: Molloy
authors.forename: John Grimley
authors.initials: JG
authors.lastname: Evans
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003072:Cognition Disorders / Q000209:etiology*; D015331:Cohort Studies; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood; D014805:Vitamin B 12 / Q000097:blood*; D014806:Vitamin B 12 Deficiency / Q000150:complications*
chemical_list: D006710:Homocysteine; D008764:Methylmalonic Acid; D014805:Vitamin B 12