Fall Frequency, Risk Factors, and Outcomes in Parkinson’s Disease: A Cross-Sectional Analysis

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ABSTRACT Background Falls are a major source of morbidity in Parkinson’s disease (PD), yet their evolution over time remains unclear. Objectives To compare fall risk and outcomes among PD, prodromal alpha-synucleinopathy, (PAS) and healthy controls (HC); estimate fall frequency across PD progression; and characterize clinical features of PD faller subgroups. Methods We analyzed fall-related outcomes in the Parkinson’s Progression Markers Initiative. Yearly rates of rare and frequent falls were estimated by time since diagnosis. Unique PD participants were grouped as never, rare, or frequent fallers. Clinical variables included motor, cognitive, behavioral, sleep, and autonomic measures. Outcomes included injuries and healthcare utilization. Regression models adjusted for age, sex, and disease duration, with Benjamini-Hochberg correction. Results Across 6,977 visits from 3,100 participants (937 PD, 1,926 PAS, 237 HC), PD participants had higher odds of falling than PAS (OR=1.66, 95% CI [1.46–1.87]) and HC (OR=4.03, 95% CI [3.14–5.23]). PD participants were also more likely to report fall-related injuries and healthcare use than PAS (OR=1.70, 1.71) and HC (OR=3.26, 3.81). Falls occurred in 15.5% of visits at diagnosis and 69.2% after 14 years, increasing across Neuronal Synuclein Disease-Integrated Staging System (NSD-ISS) stages. Frequent fallers had longer disease duration, higher NSD-ISS, and worse clinical profiles. Women were more likely to fall than men (46.1% vs 34.9%, p=0.002) despite milder symptoms. Conclusion Falls and related morbidity increase with disease duration and NSD-ISS. Risk reflects sex and motor and non-motor factors, supporting a multifactorial model. Fall frequency may represent a practical marker of progression and guide prevention strategies in PD.

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