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August 2021; 11 (4) Research

Clinical Diagnostic Accuracy of Early/Advanced Parkinson Disease

An Updated Clinicopathologic Study

Charles H. Adler, Thomas G. Beach, Nan Zhang, Holly A. Shill, Erika Driver-Dunckley, Shyamal H. Mehta, Alireza Atri, John N. Caviness, Geidy Serrano, David R. Shprecher, Lucia I. Sue, Christine M. Belden
First published October 30, 2020, DOI: https://doi.org/10.1212/CPJ.0000000000001016
Charles H. Adler
Parkinson's Disease and Movement Disorders Center (CHA, EDD, SHM), Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Civin Laboratory for Neuropathology (TGB, GS, LIS), Banner Sun Health Research Institute, Sun City, AZ; Department of Biostatistics (NZ), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Barrow Neurologic Institute (HAS), Phoenix, AZ; Cleo Roberts Center (AA, DRS, CMB), Banner Sun Health Research Institute, Sun City, AZ; and Center for Brain/Mind Medicine (AA), Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
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Thomas G. Beach
Parkinson's Disease and Movement Disorders Center (CHA, EDD, SHM), Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Civin Laboratory for Neuropathology (TGB, GS, LIS), Banner Sun Health Research Institute, Sun City, AZ; Department of Biostatistics (NZ), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Barrow Neurologic Institute (HAS), Phoenix, AZ; Cleo Roberts Center (AA, DRS, CMB), Banner Sun Health Research Institute, Sun City, AZ; and Center for Brain/Mind Medicine (AA), Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
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Nan Zhang
Parkinson's Disease and Movement Disorders Center (CHA, EDD, SHM), Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Civin Laboratory for Neuropathology (TGB, GS, LIS), Banner Sun Health Research Institute, Sun City, AZ; Department of Biostatistics (NZ), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Barrow Neurologic Institute (HAS), Phoenix, AZ; Cleo Roberts Center (AA, DRS, CMB), Banner Sun Health Research Institute, Sun City, AZ; and Center for Brain/Mind Medicine (AA), Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
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Holly A. Shill
Parkinson's Disease and Movement Disorders Center (CHA, EDD, SHM), Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Civin Laboratory for Neuropathology (TGB, GS, LIS), Banner Sun Health Research Institute, Sun City, AZ; Department of Biostatistics (NZ), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Barrow Neurologic Institute (HAS), Phoenix, AZ; Cleo Roberts Center (AA, DRS, CMB), Banner Sun Health Research Institute, Sun City, AZ; and Center for Brain/Mind Medicine (AA), Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
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Erika Driver-Dunckley
Parkinson's Disease and Movement Disorders Center (CHA, EDD, SHM), Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Civin Laboratory for Neuropathology (TGB, GS, LIS), Banner Sun Health Research Institute, Sun City, AZ; Department of Biostatistics (NZ), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Barrow Neurologic Institute (HAS), Phoenix, AZ; Cleo Roberts Center (AA, DRS, CMB), Banner Sun Health Research Institute, Sun City, AZ; and Center for Brain/Mind Medicine (AA), Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
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Shyamal H. Mehta
Parkinson's Disease and Movement Disorders Center (CHA, EDD, SHM), Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Civin Laboratory for Neuropathology (TGB, GS, LIS), Banner Sun Health Research Institute, Sun City, AZ; Department of Biostatistics (NZ), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Barrow Neurologic Institute (HAS), Phoenix, AZ; Cleo Roberts Center (AA, DRS, CMB), Banner Sun Health Research Institute, Sun City, AZ; and Center for Brain/Mind Medicine (AA), Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
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Alireza Atri
Parkinson's Disease and Movement Disorders Center (CHA, EDD, SHM), Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Civin Laboratory for Neuropathology (TGB, GS, LIS), Banner Sun Health Research Institute, Sun City, AZ; Department of Biostatistics (NZ), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Barrow Neurologic Institute (HAS), Phoenix, AZ; Cleo Roberts Center (AA, DRS, CMB), Banner Sun Health Research Institute, Sun City, AZ; and Center for Brain/Mind Medicine (AA), Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
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John N. Caviness
Parkinson's Disease and Movement Disorders Center (CHA, EDD, SHM), Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Civin Laboratory for Neuropathology (TGB, GS, LIS), Banner Sun Health Research Institute, Sun City, AZ; Department of Biostatistics (NZ), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Barrow Neurologic Institute (HAS), Phoenix, AZ; Cleo Roberts Center (AA, DRS, CMB), Banner Sun Health Research Institute, Sun City, AZ; and Center for Brain/Mind Medicine (AA), Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
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Geidy Serrano
Parkinson's Disease and Movement Disorders Center (CHA, EDD, SHM), Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Civin Laboratory for Neuropathology (TGB, GS, LIS), Banner Sun Health Research Institute, Sun City, AZ; Department of Biostatistics (NZ), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Barrow Neurologic Institute (HAS), Phoenix, AZ; Cleo Roberts Center (AA, DRS, CMB), Banner Sun Health Research Institute, Sun City, AZ; and Center for Brain/Mind Medicine (AA), Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
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David R. Shprecher
Parkinson's Disease and Movement Disorders Center (CHA, EDD, SHM), Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Civin Laboratory for Neuropathology (TGB, GS, LIS), Banner Sun Health Research Institute, Sun City, AZ; Department of Biostatistics (NZ), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Barrow Neurologic Institute (HAS), Phoenix, AZ; Cleo Roberts Center (AA, DRS, CMB), Banner Sun Health Research Institute, Sun City, AZ; and Center for Brain/Mind Medicine (AA), Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
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Lucia I. Sue
Parkinson's Disease and Movement Disorders Center (CHA, EDD, SHM), Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Civin Laboratory for Neuropathology (TGB, GS, LIS), Banner Sun Health Research Institute, Sun City, AZ; Department of Biostatistics (NZ), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Barrow Neurologic Institute (HAS), Phoenix, AZ; Cleo Roberts Center (AA, DRS, CMB), Banner Sun Health Research Institute, Sun City, AZ; and Center for Brain/Mind Medicine (AA), Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
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Christine M. Belden
Parkinson's Disease and Movement Disorders Center (CHA, EDD, SHM), Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Civin Laboratory for Neuropathology (TGB, GS, LIS), Banner Sun Health Research Institute, Sun City, AZ; Department of Biostatistics (NZ), Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale; Barrow Neurologic Institute (HAS), Phoenix, AZ; Cleo Roberts Center (AA, DRS, CMB), Banner Sun Health Research Institute, Sun City, AZ; and Center for Brain/Mind Medicine (AA), Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
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Citation
Clinical Diagnostic Accuracy of Early/Advanced Parkinson Disease
An Updated Clinicopathologic Study
Charles H. Adler, Thomas G. Beach, Nan Zhang, Holly A. Shill, Erika Driver-Dunckley, Shyamal H. Mehta, Alireza Atri, John N. Caviness, Geidy Serrano, David R. Shprecher, Lucia I. Sue, Christine M. Belden
Neurol Clin Pract Aug 2021, 11 (4) e414-e421; DOI: 10.1212/CPJ.0000000000001016

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Abstract

Objective To update data for diagnostic accuracy of a clinical diagnosis of Parkinson disease (PD) using neuropathologic diagnosis as the gold standard.

Methods Data from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) were used to determine the predictive value of a clinical PD diagnosis. Two clinical diagnostic confidence levels were used, possible PD (PossPD, never treated or not responsive) and probable PD (ProbPD, 2/3 cardinal clinical signs and responsive to dopaminergic medications). Neuropathologic diagnosis was the gold standard.

Results Based on the first visit to AZSAND, 15/54 (27.8%) PossPD participants and 138/163 (84.7%) ProbPD participants had confirmed PD. PD was confirmed in 24/34 (70.6%) ProbPD with <5 years and 114/128 (89.1%) with ≥5 years disease duration. Using the consensus final clinical diagnosis following death, 161/187 (86.1%) ProbPD had neuropathologically confirmed PD. Diagnostic accuracy for ProbPD improved if included motor fluctuations, dyskinesias, and hyposmia, and hyposmia for PossPD.

Conclusions This updated study confirmed lower clinical diagnostic accuracy for elderly, untreated or poorly responsive PossPD participants and for ProbPD with <5 years of disease duration, even when medication responsive. Caution continues to be needed when interpreting clinical studies of PD, especially studies of early disease, that do not have autopsy confirmation.

Classification of Evidence This study provides Class II evidence that a clinical diagnosis of ProbPD at the first visit identifies participants who will have pathologically confirmed PD with a sensitivity of 82.6% and a specificity of 86.0%.

Footnotes

  • Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.

  • Class of Evidence: NPub.org/coe

  • Received July 22, 2020.
  • Accepted October 1, 2020.
  • © 2021 American Academy of Neurology
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