title: Gray and white matter imaging: A biomarker for cognitive impairment in early Parkinson's disease?
abstract: BACKGROUND
  The aim of this work was to investigate the cortical and white matter changes that underlie cognitive impairment in patients with incident Parkinson's disease (PD) disease using voxel-based morphometry and diffusion tensor imaging.
  
  
  METHODS
  Newly diagnosed nondemented PD (n = 125) and control subjects (n = 50) were recruited from the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation in Parkinson's Disease Study and completed cognitive assessments and 3T structural and diffusion tensor MR imaging. Voxel-based morphometry was performed to investigate the relationship between gray matter volume and cognitive ability. Microstructural white matter changes were assessed with diffusion tensor imaging measures of fractional anisotropy and mean diffusivity using tract-based spatial statistics.
  
  
  RESULTS
  Increased mean diffusivity was observed bilaterally in subjects with PD, relative to controls (P = 0.019). Increased mean diffusivity was associated with performance on the semantic fluency and Tower of London tasks in frontal and parietal white matter tracts, including the cingulum, superior longitudinal fasciculus, inferior longitudinal fasciculus, and inferior fronto-occipital fasciculus. There was no difference in total gray matter volume between groups; however, bilateral reductions in frontal and parietal gray matter volume were associated with reduced performance on measures of executive function in PD subjects.
  
  
  CONCLUSIONS
  At the earliest stages of PD, regionally specific increases in central white matter mean diffusivity are present and suggest early axonal damage. Such changes are not accompanied by significant gray matter volume loss and are consistent with proposed models of pathological progression of the disease. Structural MRI, especially diffusion tensor imaging analysis, offers potential as a noninvasive biomarker reflecting cognitive impairment in PD.
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle, United Kingdom.|Medicine of the Elderly, Western General Hospital, Edinburgh, United Kingdom.
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Duncan
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle, United Kingdom.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Firbank
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle, United Kingdom.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Yarnall
authors.affiliation: School of Medicine and Griffith Health Institute, Griffith University, Gold Coast, Australia.
authors.forename: Tien K
authors.initials: TK
authors.lastname: Khoo
authors.affiliation: Aarhus University, Aarhus, Denmark and Imperial College, London, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.affiliation: John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Barker
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Burn
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle, United Kingdom.|Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: John T
authors.initials: JT
authors.lastname: O'Brien
mesh_terms: D000368:Aged; D001931:Brain Mapping; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology*; D015331:Cohort Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications*; D012720:Severity of Illness Index; D066127:White Matter / Q000473:pathology*
keywords: DWI; MCI (mild cognitive impairment); Parkinson's disease with dementia; Parkinson's disease/parkinsonism; magnetic resonance imaging