Clinical correlates of global and axial levodopa response in Parkinson's disease.

Abstract

Background: Levodopa response (LDR) is central to the clinical assessment of Parkinson's disease (PD), yet the factors influencing axial motor responsiveness remain insufficiently explored.

Objective: To identify clinical determinants of overall LDR and the levodopa response of axial symptoms (LDR-axial).

Methods: Consecutive PD patients evaluated between January and August 2024 were included. MDS-UPDRS-3 was administered in defined "off" and suprathreshold "on" states. LDR and LDR-axial were calculated as proportional score changes. Motor, non-motor, and cognitive variables were analyzed using multiple regression models.

Results: Forty-five patients (mean age 61.9 ± 8.6 years) were enrolled. The mean LDR was 0.36 ± 0.14, and the median LDR-axial was 0.27. Group comparisons did not reveal significant differences. In regression analyses, the Non-Motor Symptoms Scale (NMSS) was the only independent predictor of overall LDR (β = -0.407). For LDR-axial, semantic fluency emerged as the sole significant predictor (β = 0.332), and patients with limited axial improvement had significantly lower semantic fluency scores.

Conclusions: Higher non-motor symptom burden is associated with reduced dopaminergic motor responsiveness. Semantic fluency correlates with LDR-axial, suggesting a potential cognitive marker linked to nondopaminergic mechanisms underlying axial symptom resistance. These findings warrant further investigation in larger cohorts.