Homocysteine and progression of generalized small-vessel disease: the SMART-MR Study

Neurology. 2014 Mar 4;82(9):777-83. doi: 10.1212/WNL.0000000000000168. Epub 2014 Jan 29.


Objectives: Assuming the involvement of homocysteine in a generalized small-vessel disease, we investigated the association of homocysteine levels with progression of white matter lesions, lacunar infarcts, and kidney disease.

Methods: Within the SMART-MR (Second Manifestations of ARTerial disease-Magnetic Resonance) Study, a prospective cohort study on brain aging in patients with symptomatic atherosclerotic disease, 663 patients (aged 57 ± 9 years) had vascular screening and 1.5-tesla MRI at baseline and after a mean follow-up of 3.9 years. Multiple regression analysis was used to estimate the longitudinal association between total homocysteine level, defined as a continuous variable and as hyperhomocysteinemia (the highest quintile of homocysteine), and progression of white matter lesion volume, lacunar infarcts, and estimated glomerular filtration rate.

Results: After adjusting for age, sex, follow-up time, and vascular risk factors, hyperhomocysteinemia was significantly associated with increased risk of white matter lesion progression (odds ratio 2.4, 95% confidence interval [CI] 1.5-4.1) and lower estimated glomerular filtration rate at follow-up (B = -3.4 mL/min, 95% CI -5.9 to -0.9) and borderline significantly associated with new lacunar infarcts (odds ratio 1.8, 95% CI 0.9-3.4).

Conclusions: Our findings implicate a role for homocysteine in the development of a generalized small-vessel disease in which both brain and kidney are affected.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Atrophy / blood
  • Atrophy / complications
  • Atrophy / pathology
  • Brain / pathology*
  • Cerebrovascular Disorders / blood*
  • Cerebrovascular Disorders / complications
  • Cerebrovascular Disorders / pathology
  • Disease Progression
  • Female
  • Homocysteine / blood*
  • Humans
  • Hyperhomocysteinemia / blood
  • Hyperhomocysteinemia / complications
  • Hyperhomocysteinemia / pathology*
  • Kidney Diseases / blood*
  • Kidney Diseases / complications
  • Kidney Diseases / pathology
  • Male
  • Middle Aged
  • Nerve Fibers, Myelinated / pathology*
  • Prospective Studies
  • Risk Factors
  • Sex Factors


  • Homocysteine

Supplementary concepts

  • Homocysteinemia