Khalil, Rana M.Shulman, Lisa M.Gruber-Baldini, Ann L.Hausdorff, Jeffrey M.von Coelln, RainerCummings, Michael P.Parkinson's Disease (PD) and other forms of parkinsonism share characteristic motor symptoms, including tremor, bradykinesia, and rigidity. This overlap in the clinical presentation creates a diagnostic challenge, underscoring the need for objective differentiation tools. In this study, we analyzed wearable sensor data collected during mobility testing from 260 PD participants and 18 participants with etiologically diverse forms of parkinsonism. Our findings illustrate that machine learning-based analysis of data from a single wearable sensor can effectively distinguish idiopathic PD from non-PD parkinsonism with a balanced accuracy of 83.5%, comparable to expert diagnosis. Moreover, we found that diagnostic performance can be improved through severity-based partitioning of participants, achieving a balanced accuracy of 95.9%, 91.2% and 100% for mild, moderate and severe cases, respectively. Beyond its diagnostic implications, our results suggest the possibility of streamlining the testing protocol by using the Timed Up and Go test as a single mobility task. Furthermore, we present a detailed analysis of several case studies of challenging scenarios commonly encountered in clinical practice, including diagnostic uncertainty at the initial visit, and changes in clinical diagnosis at a subsequent visit. Together, these findings demonstrate the potential of applying machine learning on sensor-based measures of mobility to distinguish between PD and other forms of parkinsonism.en-USDataset