Identification of responsive motor symptom assessment items reflecting plasma levodopa changes in individuals with Parkinson’s disease

• Levodopa challenge tested along with plasma concentration monitoring. • Selected MDS-UPDRS motor items evaluated for dopaminergic responsiveness. • Rigidity showed consistent responsiveness, regardless of tremor status. • Rigidity may therefore serve as a robust clinical marker of levodopa effect in PD. Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms, including tremors, rigidity, and bradykinesia. Although levodopa remains the gold standard treatment, clinical practice highly depends on subjective patient reporting to assess medication effectiveness, which can be unreliable owing to cognitive decline and motivational factors. We aimed to identify motor symptom assessment variables within the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) framework that reliably reflect plasma levodopa concentration changes in individuals with PD. Forty-seven participants with PD underwent standardized levodopa challenge testing with concurrent plasma concentration monitoring. Motor symptoms were evaluated using a simplified assessment protocol based on selected MDS-UPDRS variables. Subgroup analysis by baseline tremor status revealed that rigidity demonstrated the most consistent responsiveness across all patient groups, showing large effect sizes (ES) regardless of baseline characteristics (overall ES: 0.65, 57.4% improvement; baseline tremor-absent ES: 0.66, 56.8% improvement; baseline tremor-present ES: 0.62, 60.0% improvement), whereas tremor and bradykinesia effectiveness varied considerably by subgroup. Rigidity assessment within the MDS-UPDRS framework may serve as a robust clinical indicator for monitoring dopaminergic responsiveness, and thereby provide a practical tool to complement subjective patient reporting to enable individualized PD management.