Low clinical diagnostic accuracy of early vs advanced Parkinson disease: Clinicopathologic study

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%.