Objective: To systematically evaluate clinical, biomarker, and treatment-related predictors of LID in patients with PD.

Background: Levodopa-induced dyskinesia (LID) is a common complication of long-term levodopa therapy in Parkinson’s disease (PD) and remains a major challenge in disease management. Identifying predictors of LID may help individualizing treatment strategies and improve long-term outcomes. While genetic determinants have been previously explored in meta-analyses, a comprehensive synthesis of non-genetic predictors remains limited.

Method: A systematic review and meta-analysis of observational studies investigating predictors of LID in PD was conducted. A comprehensive search of PubMed, Scopus, and Web of Science was performed from database inception to March 2026. Pooled effect estimates were calculated using inverse variance methods with fixed- or random-effects models according to heterogeneity. Odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs) were synthesized.

Results: A total of 41 studies involving 12,111 participants were included. Earlier age at PD onset was significantly associated with increased LID risk (OR 1.04, 95% CI 1.02–1.05). Female sex was a significant predictor (OR 1.37, 95% CI 1.22–1.53). Greater disease severity was associated with higher LID risk, including higher Hoehn and Yahr stage (OR 1.42, 95% CI 1.25–1.61) and higher UPDRS III scores (OR 1.04, 95% CI 1.02–1.06). The postural instability gait disorder (PIGD) subtype showed a strong association with LID development (HR 2.43, 95% CI 1.79–3.30), whereas tremor-dominant PD (OR 0.32, 95% CI 0.24–0.43) and mixed subtype (OR 0.49, 95% CI 0.32–0.77) were associated with lower risk. Reduced dopamine transporter availability in the posterior putamen was also associated with LID (HR 0.66, 95% CI 0.55–0.79). Higher uric acid levels (OR 1.42, 95% CI 1.15–1.76) and use of COMT inhibitors (OR 1.91, 95% CI 1.00–3.63) were additional predictors. Other variables including levodopa duration and dopamine agonist use were not significantly associated with LID.

Conclusion: Younger age at onset, female sex, greater disease severity, the PIGD phenotype, and reduced striatal dopaminergic availability are key predictors of LID in PD. These findings may help identify high-risk patients and support individualized therapeutic strategies aimed at delaying dyskinesia development.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/predictors-of-levodopa-induced-dyskinesia-in-parkinsons-disease-a-systematic-review-and-meta-analysis/