title: Association of Anterior Cingulate Glutathione with Sleep Apnea in Older Adults At-Risk for Dementia.
abstract: OBJECTIVE
  Sleep disordered breathing (SDB) is common in older adults and is strongly associated with cognitive decline, with increasing evidence suggesting that it may represent a risk factor for dementia. Given that SDB is characterized by intermittent episodes of hypoxemia during sleep, it is possible that cognitive impairment may relate to cerebral oxidative stress. This study aimed to examine the relationship between nocturnal markers of hypoxemia and proton magnetic resonance spectroscopy ((1)H-MRS) markers of oxidative stress within the anterior cingulate cortex (ACC) of the brain.
  
  
  METHODS
  Twenty-four older adults (mean age = 67.9 y) at-risk for dementia were recruited from our Healthy Brain Ageing Research Clinic. At-risk was defined as participants seeking help for assessment and/or intervention for cognitive decline, including those with subjective and/or objective cognitive complaints. This could occur in the context of prior depression or risk factors (e.g., vascular) for dementia. All participants underwent psychiatric, medical and neuropsychological assessment followed by overnight polysomnography. In addition, participants underwent (1)H-MRS to derive levels of ACC metabolite glutathione (GSH) reported as a ratio to creatine (GSH/Cr).
  
  
  RESULTS
  Increased levels of GSH/Cr were associated with lower oxygen desaturation (r = -0.54, P = 0.007) and more severe apnea-hypopnea index scores during rapid eye movement sleep (r = 0.42, P = 0.050). In addition, ACC GSH/Cr correlated with poorer executive functioning (i.e., response inhibition: r = -0.49, P = 0.015; set shifting: r = -0.43, P = 0.037).
  
  
  CONCLUSIONS
  Markers of nocturnal hypoxemia and SDB are associated with cerebral oxidative stress in older people at-risk for dementia, suggesting a potential mechanism by which SDB may contribute to brain degeneration, cognitive decline, and dementia. Further work focused on utilizing this biomarker for the early identification and treatment of this possible modifiable risk factor in older persons is now warranted.
authors: Healthy Brain Ageing Program, The University of Sydney, Camperdown, Australia.|Clinical Research Unit, Brain and Mind Centre, The University of Sydney, Camperdown, Australia.|Charles Perkins Centre, School of Psychology, The University of Sydney, Camperdown, Australia.|National Health and Medical Research Council Centre of Research Excellence 'Neurosleep', The University of Sydney, Camperdown, Australia.
authors: Shantel L
authors: SL
authors: Duffy
authors: Clinical Research Unit, Brain and Mind Centre, The University of Sydney, Camperdown, Australia.|National Health and Medical Research Council Centre of Research Excellence 'Neurosleep', The University of Sydney, Camperdown, Australia.
authors: Jim
authors: J
authors: Lagopoulos
authors: Healthy Brain Ageing Program, The University of Sydney, Camperdown, Australia.|Clinical Research Unit, Brain and Mind Centre, The University of Sydney, Camperdown, Australia.|Charles Perkins Centre, School of Psychology, The University of Sydney, Camperdown, Australia.
authors: Zoe
authors: Z
authors: Terpening
authors: Healthy Brain Ageing Program, The University of Sydney, Camperdown, Australia.|Clinical Research Unit, Brain and Mind Centre, The University of Sydney, Camperdown, Australia.|National Health and Medical Research Council Centre of Research Excellence 'Neurosleep', The University of Sydney, Camperdown, Australia.
authors: Simon J G
authors: SJ
authors: Lewis
authors: Woolcock Institute of Medical Research, Sydney Medical School, The University of Sydney, Camperdown, Australia.|National Health and Medical Research Council Centre of Research Excellence 'Neurosleep', The University of Sydney, Camperdown, Australia.
authors: Ron
authors: R
authors: Grunstein
authors: Healthy Brain Ageing Program, The University of Sydney, Camperdown, Australia.|Clinical Research Unit, Brain and Mind Centre, The University of Sydney, Camperdown, Australia.|Charles Perkins Centre, School of Psychology, The University of Sydney, Camperdown, Australia.
authors: Loren
authors: L
authors: Mowszowski
authors: Healthy Brain Ageing Program, The University of Sydney, Camperdown, Australia.|Clinical Research Unit, Brain and Mind Centre, The University of Sydney, Camperdown, Australia.|Charles Perkins Centre, School of Psychology, The University of Sydney, Camperdown, Australia.|Woolcock Institute of Medical Research, Sydney Medical School, The University of Sydney, Camperdown, Australia.|National Health and Medical Research Council Centre of Research Excellence 'Neurosleep', The University of Sydney, Camperdown, Australia.
authors: Nathan
authors: N
authors: Cross
authors: Clinical Research Unit, Brain and Mind Centre, The University of Sydney, Camperdown, Australia.
authors: Daniel F
authors: DF
authors: Hermens
authors: Healthy Brain Ageing Program, The University of Sydney, Camperdown, Australia.|Clinical Research Unit, Brain and Mind Centre, The University of Sydney, Camperdown, Australia.|National Health and Medical Research Council Centre of Research Excellence 'Neurosleep', The University of Sydney, Camperdown, Australia.
authors: Ian B
authors: IB
authors: Hickie
authors: Healthy Brain Ageing Program, The University of Sydney, Camperdown, Australia.|Clinical Research Unit, Brain and Mind Centre, The University of Sydney, Camperdown, Australia.|Charles Perkins Centre, School of Psychology, The University of Sydney, Camperdown, Australia.|National Health and Medical Research Council Centre of Research Excellence 'Neurosleep', The University of Sydney, Camperdown, Australia.
authors: Sharon L
authors: SL
authors: Naismith
mesh_terms: D000368:Aged; D000375:Aging / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D003072:Cognition Disorders / Q000150:complications / Q000175:diagnosis / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000150:complications / Q000175:diagnosis / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D003704:Dementia / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism; D003863:Depression / Q000150:complications; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000378:metabolism; D008297:Male; D009483:Neuropsychological Tests; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D017286:Polysomnography; D066244:Proton Magnetic Resonance Spectroscopy; D012307:Risk Factors; D012891:Sleep Apnea Syndromes / Q000150:complications* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D005978:Glutathione; D003401:Creatine; D010100:Oxygen
keywords: anterior cingulate cortex; executive function; glutathione; oxidative stress; oxygen desaturation; proton magnetic resonance spectroscopy; sleep apnea