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July 29, 2014; 83 (5) Article

Low clinical diagnostic accuracy of early vs advanced Parkinson disease

Clinicopathologic study

Charles H. Adler, Thomas G. Beach, Joseph G. Hentz, Holly A. Shill, John N. Caviness, Erika Driver-Dunckley, Marwan N. Sabbagh, Lucia I. Sue, Sandra A. Jacobson, Christine M. Belden, Brittany N. Dugger
First published June 27, 2014, DOI: https://doi.org/10.1212/WNL.0000000000000641
Charles H. Adler
From the Parkinson's Disease and Movement Disorders Center, Department of Neurology (C.H.A., J.N.C., E.D.-D.), and Department of Biostatistics (J.G.H.), Mayo Clinic, Scottsdale; Civin Laboratory for Neuropathology (T.G.B., L.I.S., B.N.D.) and Cleo Roberts Center (H.A.S., M.N.S., S.A.J., C.M.B.), Banner Sun Health Research Institute, Sun City, AZ; and University of Arizona College of Medicine (H.A.S., M.N.S., S.A.J.), Phoenix.
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Thomas G. Beach
From the Parkinson's Disease and Movement Disorders Center, Department of Neurology (C.H.A., J.N.C., E.D.-D.), and Department of Biostatistics (J.G.H.), Mayo Clinic, Scottsdale; Civin Laboratory for Neuropathology (T.G.B., L.I.S., B.N.D.) and Cleo Roberts Center (H.A.S., M.N.S., S.A.J., C.M.B.), Banner Sun Health Research Institute, Sun City, AZ; and University of Arizona College of Medicine (H.A.S., M.N.S., S.A.J.), Phoenix.
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Joseph G. Hentz
From the Parkinson's Disease and Movement Disorders Center, Department of Neurology (C.H.A., J.N.C., E.D.-D.), and Department of Biostatistics (J.G.H.), Mayo Clinic, Scottsdale; Civin Laboratory for Neuropathology (T.G.B., L.I.S., B.N.D.) and Cleo Roberts Center (H.A.S., M.N.S., S.A.J., C.M.B.), Banner Sun Health Research Institute, Sun City, AZ; and University of Arizona College of Medicine (H.A.S., M.N.S., S.A.J.), Phoenix.
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Holly A. Shill
From the Parkinson's Disease and Movement Disorders Center, Department of Neurology (C.H.A., J.N.C., E.D.-D.), and Department of Biostatistics (J.G.H.), Mayo Clinic, Scottsdale; Civin Laboratory for Neuropathology (T.G.B., L.I.S., B.N.D.) and Cleo Roberts Center (H.A.S., M.N.S., S.A.J., C.M.B.), Banner Sun Health Research Institute, Sun City, AZ; and University of Arizona College of Medicine (H.A.S., M.N.S., S.A.J.), Phoenix.
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John N. Caviness
From the Parkinson's Disease and Movement Disorders Center, Department of Neurology (C.H.A., J.N.C., E.D.-D.), and Department of Biostatistics (J.G.H.), Mayo Clinic, Scottsdale; Civin Laboratory for Neuropathology (T.G.B., L.I.S., B.N.D.) and Cleo Roberts Center (H.A.S., M.N.S., S.A.J., C.M.B.), Banner Sun Health Research Institute, Sun City, AZ; and University of Arizona College of Medicine (H.A.S., M.N.S., S.A.J.), Phoenix.
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Erika Driver-Dunckley
From the Parkinson's Disease and Movement Disorders Center, Department of Neurology (C.H.A., J.N.C., E.D.-D.), and Department of Biostatistics (J.G.H.), Mayo Clinic, Scottsdale; Civin Laboratory for Neuropathology (T.G.B., L.I.S., B.N.D.) and Cleo Roberts Center (H.A.S., M.N.S., S.A.J., C.M.B.), Banner Sun Health Research Institute, Sun City, AZ; and University of Arizona College of Medicine (H.A.S., M.N.S., S.A.J.), Phoenix.
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Marwan N. Sabbagh
From the Parkinson's Disease and Movement Disorders Center, Department of Neurology (C.H.A., J.N.C., E.D.-D.), and Department of Biostatistics (J.G.H.), Mayo Clinic, Scottsdale; Civin Laboratory for Neuropathology (T.G.B., L.I.S., B.N.D.) and Cleo Roberts Center (H.A.S., M.N.S., S.A.J., C.M.B.), Banner Sun Health Research Institute, Sun City, AZ; and University of Arizona College of Medicine (H.A.S., M.N.S., S.A.J.), Phoenix.
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Lucia I. Sue
From the Parkinson's Disease and Movement Disorders Center, Department of Neurology (C.H.A., J.N.C., E.D.-D.), and Department of Biostatistics (J.G.H.), Mayo Clinic, Scottsdale; Civin Laboratory for Neuropathology (T.G.B., L.I.S., B.N.D.) and Cleo Roberts Center (H.A.S., M.N.S., S.A.J., C.M.B.), Banner Sun Health Research Institute, Sun City, AZ; and University of Arizona College of Medicine (H.A.S., M.N.S., S.A.J.), Phoenix.
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Sandra A. Jacobson
From the Parkinson's Disease and Movement Disorders Center, Department of Neurology (C.H.A., J.N.C., E.D.-D.), and Department of Biostatistics (J.G.H.), Mayo Clinic, Scottsdale; Civin Laboratory for Neuropathology (T.G.B., L.I.S., B.N.D.) and Cleo Roberts Center (H.A.S., M.N.S., S.A.J., C.M.B.), Banner Sun Health Research Institute, Sun City, AZ; and University of Arizona College of Medicine (H.A.S., M.N.S., S.A.J.), Phoenix.
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Christine M. Belden
From the Parkinson's Disease and Movement Disorders Center, Department of Neurology (C.H.A., J.N.C., E.D.-D.), and Department of Biostatistics (J.G.H.), Mayo Clinic, Scottsdale; Civin Laboratory for Neuropathology (T.G.B., L.I.S., B.N.D.) and Cleo Roberts Center (H.A.S., M.N.S., S.A.J., C.M.B.), Banner Sun Health Research Institute, Sun City, AZ; and University of Arizona College of Medicine (H.A.S., M.N.S., S.A.J.), Phoenix.
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Brittany N. Dugger
From the Parkinson's Disease and Movement Disorders Center, Department of Neurology (C.H.A., J.N.C., E.D.-D.), and Department of Biostatistics (J.G.H.), Mayo Clinic, Scottsdale; Civin Laboratory for Neuropathology (T.G.B., L.I.S., B.N.D.) and Cleo Roberts Center (H.A.S., M.N.S., S.A.J., C.M.B.), Banner Sun Health Research Institute, Sun City, AZ; and University of Arizona College of Medicine (H.A.S., M.N.S., S.A.J.), Phoenix.
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Citation
Low clinical diagnostic accuracy of early vs advanced Parkinson disease
Clinicopathologic study
Charles H. Adler, Thomas G. Beach, Joseph G. Hentz, Holly A. Shill, John N. Caviness, Erika Driver-Dunckley, Marwan N. Sabbagh, Lucia I. Sue, Sandra A. Jacobson, Christine M. Belden, Brittany N. Dugger
Neurology Jul 2014, 83 (5) 406-412; DOI: 10.1212/WNL.0000000000000641

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Abstract

Objectives: Determine 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 were used to determine the predictive value of a clinical PD diagnosis, using 2 clinical diagnostic confidence levels, PossPD (never treated or not clearly responsive) and ProbPD (responsive to medications). Neuropathologic diagnosis was the gold standard.

Results: Based on first visit, 9 of 34 (26%) PossPD cases had neuropathologically confirmed PD while 80 of 97 (82%) ProbPD cases had confirmed PD. PD was confirmed in 8 of 15 (53%) ProbPD cases with <5 years of disease duration and 72 of 82 (88%) with ≥5 years of disease duration. Using final diagnosis at time of death, 91 of 107 (85%) ProbPD cases had confirmed PD. Clinical variables that improved diagnostic accuracy were medication response, motor fluctuations, dyskinesias, and hyposmia.

Conclusions: Using neuropathologic findings of PD as the gold standard, this study establishes the novel findings of only 26% accuracy for a clinical diagnosis of PD in untreated or not clearly responsive subjects, 53% accuracy in early PD responsive to medication (<5 years' duration), and >85% diagnostic accuracy of longer duration, medication-responsive PD. Caution is needed when interpreting clinical studies of PD, especially studies of early disease that do not have autopsy confirmation. The need for a tissue or other diagnostic biomarker is reinforced.

Classification of evidence: This study provides Class II evidence that a clinical diagnosis of PD identifies patients who will have pathologically confirmed PD with a sensitivity of 88% and specificity of 68%.

GLOSSARY

AZSAND=
Arizona Study of Aging and Neurodegenerative Disorders;
MSA=
multiple system atrophy;
NPV=
negative predictive value;
ParkNOS=
parkinsonism not otherwise specified;
PD=
Parkinson disease;
PossPD=
possible PD;
PPV=
positive predictive value;
ProbPD=
probable PD;
PSP=
progressive supranuclear palsy;
UPDRS=
Unified Parkinson's Disease Rating Scale;
UPSIT=
University of Pennsylvania Smell Identification Test

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 386

  • Received November 19, 2013.
  • Accepted in final form March 10, 2014.
  • © 2014 American Academy of Neurology
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