High homocysteine and low B vitamins predict cognitive decline in aging men: the Veterans Affairs Normative Aging Study

Am J Clin Nutr. 2005 Sep;82(3):627-35. doi: 10.1093/ajcn.82.3.627.


Background: Elevated homocysteine concentrations may contribute to cognitive impairment. Most elevations in homocysteine result from inadequate folate, vitamin B-12, or vitamin B-6 intake. It is not clear whether the observed associations between homocysteine and cognitive measures are causal or whether they are due to homocysteine, to independent actions of the B vitamins, or to both.

Objective: We aimed to assess the individual and independent effects of baseline plasma homocysteine, folate, vitamin B-12, and vitamin B-6 and of dietary B vitamin intakes on 3-y changes in cognitive measures in 321 aging men.

Design: Participants were from the Veterans Affairs Normative Aging Study. Cognitive function was assessed with the Mini-Mental State Examination and on the basis of measures of memory, verbal fluency, and constructional praxis, which were adapted from the revised Wechsler Adult Intelligence Scale and the Consortium to Establish a Registry for Alzheimer's Disease batteries at 2 time points. At baseline, dietary intakes were assessed with a food-frequency questionnaire, and blood was drawn for the measurement of B vitamins and homocysteine.

Results: Over a mean 3-y follow-up, declines in constructional praxis, measured by spatial copying, were significantly associated with plasma homocysteine, folate, and vitamins B-6 and B-12 and with the dietary intake of each vitamin. Folate (plasma and dietary) remained independently protective against a decline in spatial copying score after adjustment for other vitamins and for plasma homocysteine. Dietary folate was also protective against a decline in verbal fluency. A high homocysteine concentration was associated with a decline in recall memory.

Conclusions: Low B vitamin and high homocysteine concentrations predict cognitive decline. Spatial copying measures appear to be most sensitive to these effects in a general population of aging men.

Publication types

  • Comment
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / psychology*
  • Cognition / drug effects
  • Cognition / physiology*
  • Cognition Disorders / blood
  • Cognition Disorders / epidemiology
  • Cognition Disorders / etiology*
  • Cohort Studies
  • Cross-Sectional Studies
  • Diet*
  • Folic Acid / administration & dosage
  • Folic Acid / blood
  • Folic Acid Deficiency / complications
  • Follow-Up Studies
  • Homocysteine / blood*
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Vitamin B 12 / administration & dosage
  • Vitamin B 12 / blood
  • Vitamin B 6 / administration & dosage
  • Vitamin B 6 / blood
  • Vitamin B Complex / administration & dosage
  • Vitamin B Complex / blood*


  • Homocysteine
  • Vitamin B Complex
  • Vitamin B 6
  • Folic Acid
  • Vitamin B 12