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

Female sex is an independent fall risk factor in Parkinson's disease (PD), yet sex-specific fall patterns remain unclear.

To compare sex-specific fall risk and outcomes across PD, prodromal alpha-synucleinopathy (PAS), and healthy controls (HC); estimate fall frequency across PD progression; and assess how sex modifies fall risk and outcomes.

Fall outcomes were analyzed in the Parkinson's Progression Markers Initiative. Yearly rates of rare and frequent falls were estimated by time since diagnosis. PD participants were classified as never, rare, or frequent fallers. Clinical measures included motor, cognitive, behavioral, sleep, and autonomic domains. Outcomes included injuries and healthcare utilization. Regression models adjusted for age, sex, and disease duration with Benjamini-Hochberg correction.

Among 3100 participants (937 PD, 1926 PAS, 237 HC; 6977 visits), 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). In PD and PAS, females had higher odds of injuries (OR 1.50, 95% CI 1.20-1.88) and fractures (OR 1.62, 95% CI 1.15-2.29), including hip (OR 2.30, 95% CI 1.09-4.91) and upper-extremity fractures (OR 2.67, 95% CI 1.51-4.85). Within PD, falls increased with disease duration and were higher in females (7 years: 42% vs. 32%; 14 years: 88% vs. 61%) despite milder clinical profiles. Across the Neuronal Synuclein Disease-Integrated Staging System (NSD-ISS) stages, fall occurrence was higher in females.

Falls increase with disease duration and NSD-ISS stage. Female PD participants are at greater risk despite milder symptoms, supporting sex-specific prevention strategies.