Homocysteinemia is Associated with the Presence of Microbleeds in Cognitively Impaired Patients

J Stroke Cerebrovasc Dis. 2020 Dec;29(12):105302. doi: 10.1016/j.jstrokecerebrovasdis.2020.105302. Epub 2020 Sep 18.

Abstract

Background & objective: Homocysteine is possibly associated with cerebral small vessel diseases such as leukoaraiosis, silent brain infarction and cerebral microbleeds, which are in turn associated with cognitive dysfunction. We aimed to examine the relationships between cerebral microbleeds (CMBs) and plasma total homocysteine (tHcy) level, methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and cognitive function.

Methods: A total of 819 patients with memory disturbance who visited a dementia clinic consecutively were included in this study. We retrospectively collected demographic, clinical and laboratory data including tHcy level, MTHFR C677T polymorphism and Mini-Mental State Examination (MMSE). All patients underwent brain MRI including fluid attenuated inversion recovery (FLAIR) image and T2*-weighed gradient-echo (GRE) image. Logistic regression analysis was performed to test the association between risk factors and the presence of microbleeds.

Results: One hundred and sixty-one (19.7%) patients had CMBs, of whom 88 (54.7%) had CMBs in the lobar region. CMBs were more common in older hypertensive male patients with hyperhomocysteinemia. In multivariable analysis, plasma tHcy remained an independent predictor of the presence of CMBs after adjusting other confounders (OR: 1.035, 95% CI: 1.009-1.062, p = 0.009). Higher plasma tHcy level was also associated with number of CMBs, TT MTHFR genotype, and lower MMSE scores.

Conclusions: Elevated plasma tHcy level is related to high prevalence of CMBs and cognitive dysfunction. Lowering plasma tHcy could be helpful in cognitively impaired patients who have CMBs or the MTHFR TT genotype.

Keywords: MTHFR; cognition; homocysteine; microbleeds.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Cerebral Hemorrhage / diagnostic imaging
  • Cerebral Hemorrhage / epidemiology*
  • Cognition
  • Cognitive Dysfunction / diagnosis
  • Cognitive Dysfunction / epidemiology*
  • Cognitive Dysfunction / psychology
  • Female
  • Homocysteine / blood*
  • Humans
  • Hyperhomocysteinemia / blood
  • Hyperhomocysteinemia / diagnosis
  • Hyperhomocysteinemia / epidemiology*
  • Hyperhomocysteinemia / genetics
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Middle Aged
  • Polymorphism, Genetic
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Seoul / epidemiology

Substances

  • Biomarkers
  • Homocysteine
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)