Brain biochemical correlates of the plasma homocysteine level: a proton magnetic resonance spectroscopy study in the elderly subjects

Am J Geriatr Psychiatry. 2011 Jul;19(7):618-26. doi: 10.1097/JGP.0b013e318209ddf1.


Background: An elevated plasma homocysteine level has been reported to be associated with various neuropsychiatric diseases. However, little is known about the brain biochemical changes associated with the higher plasma homocysteine level. The main goal of this study was to examine the sex difference in brain biochemical concentrations using brain proton magnetic resonance spectroscopy (H MRS), and to elucidate the biochemical changes associated with plasma homocysteine levels by sex in healthy elderly subjects.

Methods: Seventy elderly subjects without any clinical psychiatric and neurological disease underwent 3-T brain H MRS. MRS spectra were acquired from voxels placed on the left side of the basal ganglia, frontal lobe, and hippocampus. Brain biochemical concentrations were compared between the elderly male and female participants. Correlations between these biochemical concentrations and plasma homocysteine levels by sex were analyzed.

Results: Female participants had significantly higher levels of choline in the left frontal lobe and hippocampus, and lower creatine and myo-inositol, in the left basal ganglia than did males. A higher homocysteine level was correlated with a lower N-acetylaspartate (NAA) concentration in the left hippocampus in elderly women (r = -0.44; p = 0.03) but not in elderly men.

Conclusions: This study found that there was a sex difference in brain biochemical concentrations in the elderly participants. A higher plasma homocysteine level was associated with a lower NAA in the hippocampus of elderly women. The sex difference in association between brain biochemical concentrations and plasma homocysteine levels needs further investigation. We speculate that after menopause, women lose protection of estrogen from the neurotoxic effects of homocysteine in the hippocampus. Future studies are required to examine this speculation.

Publication types

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

MeSH terms

  • Aged
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / blood
  • Basal Ganglia / metabolism
  • Brain / metabolism*
  • Brain / physiology
  • Choline / blood
  • Cobamides / blood
  • Creatine / blood
  • Female
  • Folic Acid / blood
  • Frontal Lobe / metabolism
  • Hippocampus / metabolism
  • Homocysteine* / blood
  • Humans
  • Inositol / blood
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Sex Characteristics


  • Cobamides
  • Homocysteine
  • Aspartic Acid
  • Inositol
  • Folic Acid
  • N-acetylaspartate
  • Creatine
  • Choline