title: Neurodegeneration across stages of cognitive decline in Parkinson disease.
abstract: OBJECTIVE
  To assess regions and patterns of brain atrophy in patients with Parkinson disease (PD) with normal cognition (PD-NC), mild cognitive impairment (PD-MCI), and dementia-level cognitive deficits (PDD).
  
  
  METHODS
  Images were quantified using a region-of-interest approach and voxel-based morphometry analysis. We used a high-dimensional pattern classification approach to delineate brain regions that collectively formed the Spatial Pattern of Abnormalities for Recognition of PDD.
  
  
  METHODS
  The Parkinson's Disease and Movement Disorders Center at the University of Pennsylvania.
  
  
  METHODS
  Eighty-four PD patients (61 PD-NC, 12 PD-MCI, and 11 PDD) and 23 healthy control subjects (HCs) underwent magnetic resonance imaging of the brain.
  
  
  RESULTS
  The PD-NC patients did not demonstrate significant brain atrophy compared with HCs. Compared with PD-NC patients, PD-MCI patients had hippocampal atrophy (β = -0.37; P = .001), and PDD patients demonstrated hippocampal (β = -0.32; P = .004) and additional medial temporal lobe atrophy (β = -0.36; P = .003). The PD-MCI patients had a different pattern of atrophy compared with PD-NC patients (P = .04) and a similar pattern to that of PDD patients (P = .81), characterized by hippocampal, prefrontal cortex gray and white matter, occipital lobe gray and white matter, and parietal lobe white matter atrophy. In nondemented PD patients, there was a correlation between memory-encoding performance and hippocampal volume.
  
  
  CONCLUSIONS
  Hippocampal atrophy is a biomarker of initial cognitive decline in PD, including impaired memory encoding and storage, suggesting heterogeneity in the neural substrate of memory impairment. Use of a pattern classification approach may allow identification of diffuse regions of cortical gray and white matter atrophy early in the course of cognitive decline.
authors.affiliation: Department of Psychiatry, University of Pennsylvania, 3615 Chestnut St, Ste 330, Philadelphia, PA 19104, USA. daniel.weintraub@uphs.upenn.edu
authors.forename: Daniel
authors.initials: D
authors.lastname: Weintraub
authors.forename: Jimit
authors.initials: J
authors.lastname: Doshi
authors.forename: Deepthi
authors.initials: D
authors.lastname: Koka
authors.forename: Christos
authors.initials: C
authors.lastname: Davatzikos
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Siderowf
authors.forename: John E
authors.initials: JE
authors.lastname: Duda
authors.forename: David A
authors.initials: DA
authors.lastname: Wolk
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Moberg
authors.forename: Sharon X
authors.initials: SX
authors.lastname: Xie
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Clark
mesh_terms: D000368:Aged; D015415:Biomarkers; D003072:Cognition Disorders / Q000145:classification / Q000175:diagnosis; D060825:Cognitive Dysfunction / Q000473:pathology / Q000523:psychology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D019636:Neurodegenerative Diseases / Q000175:diagnosis*; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000175:diagnosis* / Q000473:pathology / Q000523:psychology
chemical_list: D015415:Biomarkers