title: Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial.
abstract: BACKGROUND
  Homocysteine is a risk factor for Alzheimer's disease. In the first report on the VITACOG trial, we showed that homocysteine-lowering treatment with B vitamins slows the rate of brain atrophy in mild cognitive impairment (MCI). Here we report the effect of B vitamins on cognitive and clinical decline (secondary outcomes) in the same study.
  
  
  METHODS
  This was a double-blind, single-centre study, which included participants with MCI, aged ≥ 70 y, randomly assigned to receive a daily dose of 0.8 mg folic acid, 0.5 mg vitamin B(12) and 20 mg vitamin B(6) (133 participants) or placebo (133 participants) for 2 y. Changes in cognitive or clinical function were analysed by generalized linear models or mixed-effects models.
  
  
  RESULTS
  The mean plasma total homocysteine was 30% lower in those treated with B vitamins relative to placebo. B vitamins stabilized executive function (CLOX) relative to placebo (P = 0.015). There was significant benefit of B-vitamin treatment among participants with baseline homocysteine above the median (11.3 µmol/L) in global cognition (Mini Mental State Examination, P < 0.001), episodic memory (Hopkins Verbal Learning Test-delayed recall, P = 0.001) and semantic memory (category fluency, P = 0.037). Clinical benefit occurred in the B-vitamin group for those in the upper quartile of homocysteine at baseline in global clinical dementia rating score (P = 0.02) and IQCODE score (P = 0.01).
  
  
  CONCLUSIONS
  In this small intervention trial, B vitamins appear to slow cognitive and clinical decline in people with MCI, in particular in those with elevated homocysteine. Further trials are needed to see if this treatment will slow or prevent conversion from MCI to dementia.
authors.affiliation: OPTIMA, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK. celeste.de-jager@ndm.ox.ac.uk
authors.forename: Celeste A
authors.initials: CA
authors.lastname: de Jager
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Oulhaj
authors.forename: Robin
authors.initials: R
authors.lastname: Jacoby
authors.forename: Helga
authors.initials: H
authors.lastname: Refsum
authors.forename: A David
authors.initials: AD
authors.lastname: Smith
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D056344:Executive Function / Q000187:drug effects; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000627:therapeutic use; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D016014:Linear Models; D008297:Male; D008568:Memory / Q000187:drug effects; D014805:Vitamin B 12 / Q000097:blood / Q000627:therapeutic use; D025101:Vitamin B 6 / Q000097:blood / Q000627:therapeutic use; D014803:Vitamin B Complex / Q000097:blood / Q000627:therapeutic use*
chemical_list: D006710:Homocysteine; D014803:Vitamin B Complex; D025101:Vitamin B 6; D005492:Folic Acid; D014805:Vitamin B 12