title: Cortical Implications of Advancing Age and Disease Duration in Parkinson's Disease Patients with Postural Instability and Gait Dysfunction.
abstract: Parkinson's Disease patients with predominant gait dysfunction appear to have reduced cortical thickness compared to other motor phenotypes. The extent to which advancing age or disease duration impact the pattern of these distinctions is unclear.
  
  
  
  We examine if PD patients with predominant signs of postural instability and gait dysfunction are distinguished by distinct patterns of cerebral atrophy, and how these differences are influenced by age and disease duration.
  
  
  
  The Unified Parkinson's Disease Rating Score (UPDRS) was administered to 196 PD patients (age = 61.4±8.9yrs) in the Off and On dopamine state. All completed a structural T1-weighted brain MRI. We defined 3 motor phenotypes: tremor dominant, akinetic-rigid, and postural instability with gait disorder. General linear modeling quantified cortical thickness in relation to disease duration, and motor improvement after dopaminergic therapy. Cortical thickness and subcortical volumes were compared between the three motor subtypes, after controlling for disease duration and age.
  
  
  
  We identified 177/196 patients who met criteria for a motor subtype. When corrected for disease duration, postural-instability patients had marked cortical thinning of the bilateral frontal-temporal and posterior cortical regions (cuneus/precuneus). After regressing for age, reduced frontal thickness was evident in patients with gait dysfunction. Widespread cortical thinning was associated with increasing disease duration and reduced motor improvement to dopaminergic therapy.
  
  
  
  Results emphasize that the profile of motor signs, especially prominent gait manifestations, relate to cortical thinning in distinct regions. Unique patterns of atrophy appear to be driven by advancing pathology related to age and disease duration.
authors.affiliation: School of Medicine, University of Virginia, Charlottesville, VA, USA.
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Herb
authors.affiliation: Department of Radiology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Rane
authors.affiliation: Department of Neurology, Vanderbilt University, Nashville, TN, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Isaacs
authors.affiliation: Department of Neurology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Nelleke
authors.initials: N
authors.lastname: Van Wouwe
authors.affiliation: Department of Neurology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Olivia C
authors.initials: OC
authors.lastname: Roman
authors.affiliation: Department of Radiology, Vanderbilt University, Nashville, TN, USA.|Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
authors.forename: Bennett A
authors.initials: BA
authors.lastname: Landman
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
authors.forename: Benoit M
authors.initials: BM
authors.lastname: Dawant
authors.affiliation: Department of Neurology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Hedera
authors.affiliation: Department of Psychology, Vanderbilt University, Nashville, TN, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Zald
authors.affiliation: Department of Neurosurgery, Vanderbilt University, Nashville, TN, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Neimat
authors.affiliation: Department of Neurology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Wylie
authors.affiliation: Department of Radiology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Manus J
authors.initials: MJ
authors.lastname: Donahue
authors.affiliation: Department of Neurology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Claassen
mesh_terms: D000367:Age Factors; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D020233:Gait Disorders, Neurologic / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D010641:Phenotype; D004856:Postural Balance; D012189:Retrospective Studies
keywords: MRI; PIGD; Parkinson’s disease; gait disorders; motor phenotypes; tremor dominant