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BackgroundWe previously created the PREDIGT Score as an algorithm to predict the incidence of Parkinson disease. The model rests on a hypothesis-driven formula, [PR=(E+D+I)xGxT], that uses numerical values for five categories known to modulate Parkinson’s risk (PR): environmental exposure (E); DNA variants (D); evidence of gene-environment interactions (I); gender (G); and time (T). Notably, the formula does not rely on motor examination results.MethodsTo evaluate the PREDIGT Score, we tested it in two established case-control cohorts: ‘De Novo Parkinson Study’ (DeNoPa) and ‘Parkinson’s Progression Marker Initiative’ (PPMI). Using baseline data from 589 patients and 309 controls enrolled in the DeNoPa and PPMI cohorts, we evaluated the PREDIGT Score’s discriminative performance in distinguishing Parkinson’s patients from healthy controls by area-under-the-curve (AUC) analyses.FindingsWhen examining cohorts separately and using all available variables in each cohort to calculate the PREDIGT Score, AUCs were 0.83 (95% CI 0.77-0.89) for DeNoPa and 0.87 (95% CI 0.84-0.9) for PPMI, respectively, in distinguishing Parkinson disease patients from healthy individuals. When combining DeNoPa and PPMI data sets by using eleven variables that had been collected in both cohorts, the PREDIGT Score discriminated patients from controls with an AUC of 0.84 (95% CI 0.81-0.87). The mean score of Parkinson disease patients was significantly higher than that of control individuals at 108.48 (+52.08) and 47.33 (+34.1), respectively (p < 0.0001).InterpretationOur results demonstrate a robust performance of the original PREDIGT Score in distinguishing patients diagnosed with Parkinson disease from neurologically healthy subjects without reliance on motor examination data. In future efforts, the predictive performance of the algorithm will be studied in longitudinal cohorts of at-risk persons.FundingParkinson Canada, Michael J. Fox Foundation, Department of Medicine (The Ottawa Hospital), Uttra & Subash Bhargava Family, Paracelsus-Elena-Klinik Kassel, Parkinson Fond Deutschland, and Deutsche Parkinson Vereinigung.