Speech abnormalities in Parkinson's disease (PD) are heterogeneous and often considered resistant to levodopa. However, human hearing may miss subtle treatment-related speech changes. Digital speech biomarkers offer a sensitive alternative to measure such changes objectively. Speech was recorded in 51 PD patients during ON and OFF medication states and compared to 43 healthy controls matched for language and gender. Acute levodopa effects were significant in prosodic (F0 standard deviation, p = 0.03, effect size = 0.47), respiratory (intensity slope, p = 0.02, effect size = 0.49), and spectral domains (LTAS mean, p = 0.01, effect size = 0.35). Stepwise backward regression identified 8 biomarkers reflecting hypokinetic symptoms, 6 for dyskinetic symptoms, and 7 for medication-state transitions. Hypokinetic compound score correlated strongly with MDS-UPDRS-III changes (r = 0.70; MAE = 6.06/92), and the dyskinetic compound score with dyskinesia ratings (r = 0.50; MAE = 1.81/12). Medication-state transitions were detected with AUC = 0.86. This study highlights the potential of digital speech biomarkers to objectively measure levodopa-induced changes in PD symptoms and medication states.

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