title: Glutathione relates to neuropsychological functioning in mild cognitive impairment.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Ageing Brain Centre , Brain & Mind Research Institute, The University of Sydney, Camperdown, Australia; Clinical Research Unit, Brain & Mind Research Institute, The University of Sydney, Camperdown, Australia.
authors.forename: Shantel L
authors.initials: SL
authors.lastname: Duffy
authors.affiliation: Clinical Research Unit, Brain & Mind Research Institute, The University of Sydney, Camperdown, Australia.
authors.forename: Jim
authors.initials: J
authors.lastname: Lagopoulos
authors.affiliation: Ageing Brain Centre , Brain & Mind Research Institute, The University of Sydney, Camperdown, Australia; Clinical Research Unit, Brain & Mind Research Institute, The University of Sydney, Camperdown, Australia.
authors.forename: Ian B
authors.initials: IB
authors.lastname: Hickie
authors.affiliation: Ageing Brain Centre , Brain & Mind Research Institute, The University of Sydney, Camperdown, Australia; Clinical Research Unit, Brain & Mind Research Institute, The University of Sydney, Camperdown, Australia.
authors.forename: Keri
authors.initials: K
authors.lastname: Diamond
authors.affiliation: Ken Parker Research Laboratories, Brain & Mind Research Institute, The University of Sydney, Camperdown, Australia.
authors.forename: Manuel B
authors.initials: MB
authors.lastname: Graeber
authors.affiliation: Ageing Brain Centre , Brain & Mind Research Institute, The University of Sydney, Camperdown, Australia; Clinical Research Unit, Brain & Mind Research Institute, The University of Sydney, Camperdown, Australia.
authors.forename: Simon J G
authors.initials: SJ
authors.lastname: Lewis
authors.affiliation: Ageing Brain Centre , Brain & Mind Research Institute, The University of Sydney, Camperdown, Australia; Clinical Research Unit, Brain & Mind Research Institute, The University of Sydney, Camperdown, Australia. Electronic address: sharon.naismith@sydney.edu.au.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Naismith
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000378:metabolism* / Q000503:physiopathology*; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008569:Memory Disorders / Q000209:etiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D011522:Protons; D011569:Psychiatric Status Rating Scales; D011877:Radionuclide Imaging; D014706:Verbal Learning / Q000502:physiology
chemical_list: D011522:Protons; D005978:Glutathione
keywords: Cingulate; Glutathione; Memory; Mild cognitive impairment; Spectroscopy