biostudies-literatureBenesh ATel Aviv University Center for AI and Data ScienceBiogenIsrael Science Foundation46https://www.ebi.ac.uk/biostudies/studies/S-EPMC12910052biostudies-literatureUnknown12(1)Parkinson's disease (PD) is a highly heterogeneous condition with symptoms spanning motor and non-motor domains. Clinical scales like the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) are standard in clinical trials where disease progression is monitored. They rely on summing item values, assuming uniform item importance and score increments. Here, we propose a novel data-driven approach to optimize weights for such scales-so that total scores better reflect the underlying disease severity. In a retrospective observational analysis of longitudinal cohort data from the Parkinson's Progression Markers Initiative (PPMI), our methods identified which items (and value increments) most strongly indicate PD progression, down-weighting or excluding less informative items. The learned weights substantially improve the monotonic relationship between total scores and clinical progression. We validated our weights using both held-out PPMI data and an independent dataset (BeaT-PD), demonstrating their robustness. Applying such weights in clinical trials may increase power and reduce the required sample size¹.NPJ Parkinson's diseaseOptimizing Parkinson's disease progression scales using computational methods.PMC129100522206/22Mirelman ABenesh AShamir RAlcalay RNfalseOptimizing Parkinson's disease progression scales using computational methods.Parkinson's disease (PD) is a highly heterogeneous condition with symptoms spanning motor and non-motor domains. Clinical scales like the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) are standard in clinical trials where disease progression is monitored. They rely on summing item values, assuming uniform item importance and score increments. Here, we propose a novel data-driven approach to optimize weights for such scales-so that total scores better reflect the underlying disease severity. In a retrospective observational analysis of longitudinal cohort data from the Parkinson's Progression Markers Initiative (PPMI), our methods identified which items (and value increments) most strongly indicate PD progression, down-weighting or excluding less informative items. The learned weights substantially improve the monotonic relationship between total scores and clinical progression. We validated our weights using both held-out PPMI data and an independent dataset (BeaT-PD), demonstrating their robustness. Applying such weights in clinical trials may increase power and reduce the required sample size¹.2026-01-01T00:00:00Z2026 Jan2026-07-09T13:20:01.19Z2026-07-09T13:10:10.775ZS-EPMC129100524157768210.1038/s41531-026-01259-1