Poster #92: Arjun Paunikar

Genetic, Biochemical, and Clinical Predictors of Accelerated Progression in Parkinson's Disease: A Systematic Review and Meta-Analysis

Samhitha Sivakumar, ATLAS Research Group Rhea Jha, ATLAS Research Group Soham Gupta, ATLAS Research Group Arjun Paunikar, ATLAS Research Group Janvi Garg, BS (Biology and Mathematics, Baylor University), ATLAS Research Group, Columbia University

Parkinson's disease (PD) follows a heterogeneous clinical trajectory, and patient-level predictors of accelerated neurodegenerative progression under dopaminergic therapy remain poorly characterized. We conducted a systematic review and meta-analysis following PRISMA guidelines to identify genetic, biochemical, and clinical risk factors most consistently associated with faster motor and cognitive decline. Bibliographic databases were searched for studies published between 2008–2025, with title/abstract screening in Rayyan. Eligible studies included prospective and retrospective cohorts and multicenter registries (PPMI, PRECEPT, PROPARK, CamPaIGN) reporting hazard ratios (HR), odds ratios (OR), or equivalent estimates for progression outcomes (annual UPDRS worsening, dyskinesia onset, DAT-SPECT decline). Pooled estimates were calculated using DerSimonian-Laird random-effects models. Forty-nine studies comprising 8,647 patients (median N = 259; range 96–1,436) were included. The overall pooled HR for adverse progression was 1.42 (95% CI 1.28–1.58; p = 3.06×10⁻¹¹; I² = 87.3%). Levodopa-induced dyskinesia was the strongest predictor of cognitive decline (pooled HR/OR = 3.92; 95% CI 2.66–5.77; I² = 0.0%). GBA mutation carriers showed markedly faster progression (HR = 2.15; 95% CI 1.65–2.79). Female sex was linked to more than double the risk of motor complications (HR/OR = 2.36; I² = 0.0%). Elevated serum urate was the most consistent protective factor (HR = 0.46; 95% CI 0.35–0.60), especially in men. MAPT H1/H1 homozygosity strongly predicted dementia (OR = 12.10), and poorly controlled type 2 diabetes contributed to motor deterioration (HR ≈ 2.07). Levodopa-induced dyskinesia and GBA status represent the most consistent early risk-stratification targets, while elevated serum urate is the most reproducible protective biomarker. These findings support precision stratification approaches in dopaminergic therapy trials and disease-modification research.