Objective: To assess the predictive value of previously reported clinical and demographic predictors for levodopa-related adverse drug reactions in the Dutch multicenter Profiling Parkinson’s disease (ProPark) cohort.
Background: Levodopa-related Adverse Drug Reactions (ADRs) are common in Parkinson’s Disease (PD). However, the occurrence of ADRs shows considerable inter-individual variability and is challenging to predict for clinicians. Clinical and demographic predictors for these ADRs have been reported, but results are inconsistent and external validation in a large independent cohort is lacking. Moreover, the extent to which these predictors explain the variability in occurrence of ADRs remains largely unexplored.
Method: The baseline data of 466 PD patients using levodopa from the ProPark cohort were analysed. Logistic regression models were constructed for four levodopa-related ADRs: dyskinesia, motor fluctuations, orthostatic hypotension, and excessive daytime sleepiness. Models including previously reported clinical and demographic characteristics were evaluated with Tjur’s R2 as a measure of predictive value.
Results: The predictors of all ADRs explained limited variance across the models (Tjur’s R² 0.09-0.14). Younger age, lower BMI, and longer disease duration were associated with dyskinesia. Female sex and a higher Levodopa Equivalent Daily Dose (LEDD) were associated with motor fluctuations. Older age, REM-sleep behaviour disorder and cardiovascular autonomic dysfunction were associated with orthostatic hypotension. Older age, a higher LEDD, depressive symptoms, and autonomic dysfunction were associated with excessive daytime sleepiness.
Conclusion: Previously reported clinical and demographic predictors explain only a limited proportion of variability in ADR occurrence. Important determinants of ADR susceptibility remain unaccounted for. Future research should explore additional biological and disease-related factors, including pharmacogenomic variation, and digital biomarkers capturing real-world motor and autonomic fluctuations.
To cite this abstract in AMA style:
L. Helling, R. Weijer, J. Swen, S. Böhringer, J. van Hilten, D. Hepp. External Validation of Reported Clinical Predictors of Levodopa-Related Adverse Drug Reactions in Parkinson’s Disease [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/external-validation-of-reported-clinical-predictors-of-levodopa-related-adverse-drug-reactions-in-parkinsons-disease/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/external-validation-of-reported-clinical-predictors-of-levodopa-related-adverse-drug-reactions-in-parkinsons-disease/