Low Diagnostic Accuracy of a Clinical Diagnosis of Early Parkinson’s Disease: Findings of the Arizona Parkinson’s Disease Consortium (S37.001)

Objective: Determine the diagnostic accuracy of a clinical neurologic examination diagnosis of Parkinson’s disease (PD) using neuropathological diagnosis as the gold standard. Background: The accuracy of a clinical diagnosis of PD has significant impact on clinical care, clinical trials, and epidemiological/genetic/biomarker research studies. Design/Methods: Data from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND), an ongoing longitudinal clinical-neuropathological study, was used to determine the predictive value of an antemortem PD diagnosis, using two clinical diagnostic confidence levels, probable PD (ProbPD-responsive to dopaminergic medications) and possible PD (PossPD-never treated or not clearly responsive) and two diagnostic time points, first visit and final (postmortem) conference. For all calculations, the neuropathological diagnosis was used as the gold standard. Results: At first visit of ProbPD with a disease duration less than 5 yrs, PD was neuropathologically confirmed in only 8/15 (53%) cases. In comparison, in ProbPD with a disease duration of at least 5 yrs at first visit, PD was neuropathologically confirmed in 72/82 (88%) cases. As a whole, of 97 subjects with ProbPD at the first visit 80 (82%) had neuropathologically confirmed PD. Of ProbPD at the final visit, 91/107 (85%) had neuropathologically confirmed PD. The clinical variables that improved diagnostic accuracy were medication response, motor fluctuations, dyskinesias and hyposmia. Of PossPD cases at first visit only 9/34 (26%) followed to autopsy had neuropathologically confirmed PD. Conclusions: This study extends previous work on the diagnostic accuracy of a clinical diagnosis of PD and includes novel findings of less than 60% accuracy with shorter duration of disease and only 26% accuracy in untreated or not clearly responsive subjects. Therefore, caution is needed when interpreting clinical studies of PD that do not have autopsy confirmation and reinforce the need for a tissue or other diagnostic biomarker Study Supported by: NINDS, NIA, Arizona Biomedical Research Commission, Michael J. Fox Foundation for Parkinson’s Research, and Mayo Clinic Foundation. Disclosure: Dr. Adler has received personal compensation for activities with Merz, Impax, Teva Neuroscience, and Novartis. Dr. Adler has received research support from Avid Radiopharmaceuticals. Dr. Beach has received personal compensation for activities with GE Healthcare as a consultant. Dr. Beach has received research support from Avid Radiopharmaceuticals and GE Healthcare. Dr. Hentz has received research support from Forest Laboratories Inc., Eisai Inc., Caridian, and Millennium. Dr. Shill has received research support from Schering-Plough/Merck, Avid Radiopharmaceuticals, UCB Biosciences, and Adamas Pharmaceuticals. Dr. Caviness has received research support from Amarin Pharmaceuticals. Dr. Driver-Dunckley received research support from Allon Therapeutics, Chelsea Therapeutics, EMD Serono, and Ipsen. Dr. Sabbagh has received personal compensation for activities with Amerisciences, Pfizer Inc., Eisai Inc., Eli Lilly & Co., Avid Pharmaceuticals, Bristol-Myers Squibb Co., and Allon. Dr. Sabbagh has received royalty payments from Amerisciences and Wiley. Dr. Sabbagh has received research support from Avid, Baxter, Bayer Pharmaceuticals Inc., Bristol-Myers Squibb Co., Celgene, Eisai Inc., Elan Corp., Eli Lilly & Co., General Electric, Genentech Inc., Janssen/Wyeth Pharmaceuticals, and Pfizer Inc. Dr. Sue has nothing to disclose. Dr. Jacobson has received research support from Avid, Baxter, Bayer Pharmaceuticals Corporation, Bristol-Meyers Squibb Company, Celgene, Eisai Inc, Elan Corporation, Eli Lilly & Company, General Electric, Genentech Inc, Janssen Pharmaceutica, and Pfizer Inc. Dr. Belden has received research support from Celgene, Genentech Inc., Avid Radiopharmaceuticals, Eli Lilly & Company, GE Healthcare, Wyeth Pharmaceuticals, Bayer Pharmaceuticals Corporation, and Pfizer Inc. Dr. Dugger has nothing to disclose.