title: Stage-dependent loss of cortical gyrification as Parkinson disease "unfolds".
abstract: OBJECTIVE
  Nigrostriatal terminal losses are known to progress most rapidly in early-stage Parkinson disease (PD) and then plateau, whereas cortical pathology continues and may provide a better marker of PD progression in later stages. We investigated cortical gyrification indices in patients with different durations of PD, since cortical folding may capture complex processes involving transverse forces of neuronal sheets or underlying axonal connectivity.
  
  
  METHODS
  Longitudinal cohort structural MRI were obtained at baseline, 18 months, and 36 months from 70 patients with PD without dementia and 70 control participants. Cortical local gyrification index (LGI) was compared between controls and PD subgroups based upon duration of illness (DOI, <1 year [PDE, n = 17], 1-5 years [PDM, n = 19], >5 years [PDL, n = 24]) and adjusted using false discovery rate. Associations between LGI and clinical measurements were assessed using multiple linear regression. Areas having significantly reduced LGI also were analyzed using baseline data from a newly established cohort (PD n = 87, control n = 66) to validate our findings.
  
  
  RESULTS
  In the longitudinal cohort, PDL had significantly reduced overall gyrification, and bilaterally in the inferior parietal, postcentral, precentral, superior frontal, and supramarginal areas, compared to controls (p < 0.05). Longitudinally, loss of gyrification was accelerated in PDM participants, compared to controls. LGI showed robust correlations with DOI and also was correlated with PD-related clinical measurements. Similar results were obtained in the validation sample.
  
  
  CONCLUSIONS
  Loss of cortical gyrification may be accelerated within the first few years after PD diagnosis, and become particularly prominent in later stages. Thus, it may provide a metric for monitoring progression in vivo.
authors.affiliation: From the Departments of Neurology (N.W.S., L.Z., E.-Y.L., G.D., M.M.L., X.H.), Public Health Sciences (M.W.), Pharmacology (M.M.L., X.H.), Radiology (X.H.), Neurosurgery (X.H.), and Kinesiology (X.H.), Pennsylvania State University-Milton S. Hershey Medical Center; and Departments of Computer Science and Psychiatry (M.S.), University of North Carolina, Chapel Hill.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Sterling
authors.affiliation: From the Departments of Neurology (N.W.S., L.Z., E.-Y.L., G.D., M.M.L., X.H.), Public Health Sciences (M.W.), Pharmacology (M.M.L., X.H.), Radiology (X.H.), Neurosurgery (X.H.), and Kinesiology (X.H.), Pennsylvania State University-Milton S. Hershey Medical Center; and Departments of Computer Science and Psychiatry (M.S.), University of North Carolina, Chapel Hill.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: From the Departments of Neurology (N.W.S., L.Z., E.-Y.L., G.D., M.M.L., X.H.), Public Health Sciences (M.W.), Pharmacology (M.M.L., X.H.), Radiology (X.H.), Neurosurgery (X.H.), and Kinesiology (X.H.), Pennsylvania State University-Milton S. Hershey Medical Center; and Departments of Computer Science and Psychiatry (M.S.), University of North Carolina, Chapel Hill.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: From the Departments of Neurology (N.W.S., L.Z., E.-Y.L., G.D., M.M.L., X.H.), Public Health Sciences (M.W.), Pharmacology (M.M.L., X.H.), Radiology (X.H.), Neurosurgery (X.H.), and Kinesiology (X.H.), Pennsylvania State University-Milton S. Hershey Medical Center; and Departments of Computer Science and Psychiatry (M.S.), University of North Carolina, Chapel Hill.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Lee
authors.affiliation: From the Departments of Neurology (N.W.S., L.Z., E.-Y.L., G.D., M.M.L., X.H.), Public Health Sciences (M.W.), Pharmacology (M.M.L., X.H.), Radiology (X.H.), Neurosurgery (X.H.), and Kinesiology (X.H.), Pennsylvania State University-Milton S. Hershey Medical Center; and Departments of Computer Science and Psychiatry (M.S.), University of North Carolina, Chapel Hill.
authors.forename: Guangwei
authors.initials: G
authors.lastname: Du
authors.affiliation: From the Departments of Neurology (N.W.S., L.Z., E.-Y.L., G.D., M.M.L., X.H.), Public Health Sciences (M.W.), Pharmacology (M.M.L., X.H.), Radiology (X.H.), Neurosurgery (X.H.), and Kinesiology (X.H.), Pennsylvania State University-Milton S. Hershey Medical Center; and Departments of Computer Science and Psychiatry (M.S.), University of North Carolina, Chapel Hill.
authors.forename: Mechelle M
authors.initials: MM
authors.lastname: Lewis
authors.affiliation: From the Departments of Neurology (N.W.S., L.Z., E.-Y.L., G.D., M.M.L., X.H.), Public Health Sciences (M.W.), Pharmacology (M.M.L., X.H.), Radiology (X.H.), Neurosurgery (X.H.), and Kinesiology (X.H.), Pennsylvania State University-Milton S. Hershey Medical Center; and Departments of Computer Science and Psychiatry (M.S.), University of North Carolina, Chapel Hill.
authors.forename: Martin
authors.initials: M
authors.lastname: Styner
authors.affiliation: From the Departments of Neurology (N.W.S., L.Z., E.-Y.L., G.D., M.M.L., X.H.), Public Health Sciences (M.W.), Pharmacology (M.M.L., X.H.), Radiology (X.H.), Neurosurgery (X.H.), and Kinesiology (X.H.), Pennsylvania State University-Milton S. Hershey Medical Center; and Departments of Computer Science and Psychiatry (M.S.), University of North Carolina, Chapel Hill. xuemei@psu.edu.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Huang
mesh_terms: D000368:Aged; D002540:Cerebral Cortex / Q000473:pathology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis* / Q000453:epidemiology