Distinct temporal dynamics of motor and neuropsychiatric responses to levodopa in Parkinson’s disease
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Background
Neuropsychiatric fluctuations in Parkinson’s disease (PD) often accompany motor fluctuations, but their temporal relationship during the acute levodopa response remains unclear.
Objectives
To determine whether motor and neuropsychiatric responses occur synchronously during the OFF-to-ON transition.
Methods
Nineteen fluctuating PD patients underwent a high-resolution levodopa challenge with repeated assessments every 10 minutes for 70 minutes after levodopa administration. Motor symptoms (akinesia, rigidity) and neuropsychiatric fluctuations were quantified. Transition times (t25%-t50%-t75%-t100%) and response profiles were analyzed using correlation and clustering approaches.
Results
Motor and neuropsychiatric transition times were not correlated at any threshold (all FDR-corrected p>0.05; Bayes factors <1), supporting temporal dissociation. Among 18 patients with complete data, clustering revealed synchronous (6/18), neuropsychiatric-preceding (7/18), and motor-preceding (3/18) profiles.
Conclusion
Motor and neuropsychiatric responses to levodopa during PD fluctuations are partly independent and follow heterogeneous, patient-specific temporal profiles, supporting the search for distinct biomarkers and future individualized adaptative therapies.
