Homocysteine as a risk factor for cognitive impairment in stroke patients

Dement Geriatr Cogn Disord. 2003;15(3):155-62. doi: 10.1159/000068481.


Background: Elevated total homocysteine (tHcy) levels are associated with an increased risk of cerebrovascular disease. It is uncertain whether tHcy is also an independent risk factor for cognitive impairment.

Methods: We examined 95 stroke subjects 3 months after their strokes, and 55 healthy comparison subjects, with a detailed neuropsychological assessment, and MRI brain scans in a proportion (n = 97). Baseline measurements of tHcy, serum folate and B(12), creatinine and plasma fibrinogen levels were obtained.

Results: tHcy levels were higher in the stroke subjects by a mean 34%. These levels were significantly correlated with the first factor of a principal component analysis of the neuropsychological data, after controlling for age, folate, B(12) and creatinine levels. The correlation of Hcy levels was particularly significant with frontal-executive functioning and attention. tHcy levels were significantly correlated with number of infarcts and total stroke volume in the stroke group, but not with T(2)-weighted deep white matter hyperintensity scores, after correction for age. In the control group, tHcy levels were significantly correlated with ventricle-to-brain ratios as measures of brain atrophy.

Conclusion: This study provides evidence that high tHcy levels are associated with cognitive impairment, in particular that of frontal-executive function. The major component of this association is accounted for by small and large strokes, but non-vascular neurotoxic effects of tHcy also appear to play a role. tHcy must receive greater attention as a risk factor for cognitive impairment.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cognition Disorders / blood*
  • Cognition Disorders / diagnosis
  • Cognition Disorders / etiology
  • Female
  • Homocysteine / blood*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Risk Factors
  • Stroke / blood
  • Stroke / complications*
  • Stroke / pathology


  • Homocysteine