Glutathione relates to neuropsychological functioning in mild cognitive impairment

Shantel L. Duffy, Jim Lagopoulos, Ian B. Hickie, Keri Diamond, Manuel B. Graeber, Simon J G Lewis, Sharon L. Naismith*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

90 Citations (Scopus)


Background: Mild cognitive impairment (MCI) represents an at-risk state for Alzheimer's disease in which underlying pathophysiological mechanisms could be delineated. Oxidative stress has been implicated in Alzheimer's disease and can be measured by levels of the antioxidant glutathione. This study aims to assess in vivo levels of glutathione via proton magnetic resonance spectroscopy in patients with MCI and to determine how glutathione relates to cognitive decline. Methods: Fifty-four patients with MCI and 41 healthy control subjects underwent proton magnetic resonance spectroscopy in conjunction with medical, psychiatric, and neuropsychological assessments. The concentration of glutathione was measured in the anterior and posterior cingulate, and ratios of glutathione were calculated relative to creatine. Neuropsychological performance was assessed across the domains of processing speed, learning, memory, and executive functions. Results: In comparison with control subjects, patients with MCI had significantly elevated ratios of glutathione in the anterior (t = -2.2, P =.03) and posterior (t = -2.9, P =.005) cingulate. Higher levels of anterior cingulate glutathione were related to neuropsychological decrements on tests of executive functions. Elevated posterior cingulate glutathione was associated with poorer memory consolidation. Conclusion: This study has shown for the first time that MCI is associated with increased glutathione in the cingulate, which in turn relates to neuropsychological performance. This finding may be indicative of an early compensatory or neuroprotective response, and the role of glial cells and glutathione enzymes requires delineation. Longitudinal studies examining the utility of glutathione as a marker for cognitive decline are now required.

Original languageEnglish
Pages (from-to)67-75
Number of pages9
JournalAlzheimer's and Dementia
Issue number1
Publication statusPublished - Jan 2014
Externally publishedYes


  • Cingulate
  • Glutathione
  • Memory
  • Mild cognitive impairment
  • Spectroscopy


Dive into the research topics of 'Glutathione relates to neuropsychological functioning in mild cognitive impairment'. Together they form a unique fingerprint.

Cite this