title: Metabolite ratios in the posterior cingulate cortex do not track cognitive decline in Parkinson's disease in a clinical setting.
abstract: BACKGROUND
  Parkinson's Disease (PD) is classified as a motor disorder, but most patients develop cognitive impairment, and eventual dementia (PDD). Predictive neurobiomarkers may be useful in the identification of those patients at imminent risk of PDD. Given the compromised cerebral integrity in PDD, we investigated whether brain metabolites track disease progression over time.
  
  
  METHODS
  Proton Magnetic Resonance Spectroscopy (MRS) was used to identify brain metabolic changes associated with cognitive impairment and dementia in PD. Forty-nine healthy participants and 130 PD patients underwent serial single voxel proton MRS and neuropsychological testing. At baseline patients were classified as either having normal cognitive status (PDN, n = 77), mild cognitive impairment (PDMCI, n = 33), or dementia (PDD, n = 20). Posterior cingulate cortex (PCC) was examined to quantify N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and myo-inositol (mI). A hierarchical Bayesian model was used to assess whether cognitive ability and other covariates were related to baseline MRS values and changes in MRS over time.
  
  
  RESULTS
  At baseline, relative to controls, PDD had significantly decreased NAA/Cr and increased Cho/Cr. However, these differences did not remain significant after accounting for age, sex, and MDS-UPDRS III. At follow-up, no significant changes in MRS metabolite ratios were detected, with no relationship found between MRS measures and change in cognitive status.
  
  
  CONCLUSIONS
  Unlike Alzheimer's disease, single voxel MR spectroscopy of the PCC failed to show any significant association with cognitive status at baseline or over time. This suggests that MRS of PCC is not a clinically useful biomarker for tracking or predicting cognitive impairment in Parkinson's disease.
authors.affiliation: New Zealand Brain Research Institute, Christchurch, New Zealand; Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Almuqbel
authors.affiliation: New Zealand Brain Research Institute, Christchurch, New Zealand; Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Tracy R
authors.initials: TR
authors.lastname: Melzer
authors.affiliation: New Zealand Brain Research Institute, Christchurch, New Zealand.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Myall
authors.affiliation: New Zealand Brain Research Institute, Christchurch, New Zealand; Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Michael R
authors.initials: MR
authors.lastname: MacAskill
authors.affiliation: New Zealand Brain Research Institute, Christchurch, New Zealand; Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Toni L
authors.initials: TL
authors.lastname: Pitcher
authors.affiliation: New Zealand Brain Research Institute, Christchurch, New Zealand; Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Leslie
authors.initials: L
authors.lastname: Livingston
authors.affiliation: New Zealand Brain Research Institute, Christchurch, New Zealand; Department of Psychology, University of Canterbury, New Zealand.
authors.forename: Kyla-Louise
authors.initials: KL
authors.lastname: Wood
authors.affiliation: New Zealand Brain Research Institute, Christchurch, New Zealand; Christchurch Radiology Group, Christchurch, New Zealand.
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Keenan
authors.affiliation: New Zealand Brain Research Institute, Christchurch, New Zealand; Department of Medicine, University of Otago, Christchurch, New Zealand; Department of Psychology, University of Canterbury, New Zealand.
authors.forename: John C
authors.initials: JC
authors.lastname: Dalrymple-Alford
authors.affiliation: New Zealand Brain Research Institute, Christchurch, New Zealand; Department of Medicine, University of Otago, Christchurch, New Zealand; Department of Neurology, Christchurch Hospital, Christchurch, New Zealand. Electronic address: Tim.Anderson@cdhb.health.nz.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Anderson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001499:Bayes Theorem; D016022:Case-Control Studies; D002794:Choline / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000378:metabolism* / Q000523:psychology; D003401:Creatine / Q000378:metabolism; D003704:Dementia / Q000378:metabolism* / Q000523:psychology; D018450:Disease Progression; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D007294:Inositol / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000378:metabolism* / Q000523:psychology; D054063:Superior Sagittal Sinus
chemical_list: D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline
keywords: Longitudinal; MCI (mild cognitive impairment); Magnetic Resonance Spectroscopy (MRS); Neurobiomarker; Parkinson's Disease (PD)