ArticleNeurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology2026
Dissociating dopaminergic and nondopaminergic motor loads in Parkinson's disease: clinical correlates, non-motor interactions, and quality-of-life implications.
Article in Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundMotor heterogeneity in Parkinson's disease (PD) reflects the interplay between dopaminergic and nondopaminergic circuits. While dopaminergic therapy restores activity within basal ganglia-cortical motor pathways, residual ON-state motor impairment represents nondopaminergic dysfunction. The determinants of these two components and their relation to quality of life remain incompletely understood.
objectiveTo identify independent clinical correlates of dopaminergic and nondopaminergic motor loads and to assess their combined effects on quality of life in PD.
methodsThis retrospective study included 688 idiopathic PD patients evaluated with MDS-UPDRS (I-IV), NMSS, FOG-Q, FES-I, VHI, HAM-A, HDRS, and PDQ-39. Dopaminergic motor improvement was defined as Δ (MDS-UPDRS III OFF-ON), and residual nondopaminergic severity as ON-state MDS-UPDRS III. Multivariable regression analyses identified independent predictors and quality-of-life determinants.
resultsGreater dopaminergic improvement was associated with longer disease duration (β = 1.60, p = 0.010) and higher FOG-Q scores (β = 2.10, p = 0.001). Among NMSS domains, Sleep/Fatigue correlated positively and Mood/Cognition negatively with dopaminergic responsiveness. Residual nondopaminergic motor load was predicted by older age (β = 0.147, p < 0.001), higher FES-I and VHI scores, and NMSS Mood/Cognition and Sexual domains. In quality-of-life models, both nondopaminergic motor load (β = 0.41, p < 0.001) and total non-motor burden (β = 0.87, p < 0.001) were independent determinants of poorer PDQ-39 outcomes.
conclusionDopaminergic improvement declines with disease progression yet remains modulated by freezing-related responsiveness. Nondopaminergic motor load-shaped by axial, bulbar, and limbic-autonomic features-and overall non-motor burden jointly account for quality-of-life deterioration in PD. Addressing both dopaminergic and nondopaminergic domains is crucial for comprehensive management.
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