Background Concern about falling (CAF) is highly prevalent in multiple sclerosis (MS) and is linked to poor motor, cognitive, and psychological functioning. Although CAF has been associated with impairments in these domains, the unique and combined contributions of motor, cognitive, psychological, and neural factors remain unclear. This study used a comprehensive approach to identify behavioral and neural predictors of CAF. Methods Forty-three individuals with MS completed motor, cognitive, and psychological assessments, and underwent a structural magnetic resonance imaging scan. Linear regression models examined domain-specific predictors of CAF, controlling for disease severity. A discriminant function analysis (DFA) evaluated the combined predictive value of all variables in classifying individuals into high versus low CAF groups based on a median split. Results CAF was significantly associated with impairments across all behavioral domains (| r | = .32-.78). Regression models explained 57% to 74% of variance in CAF. Greater physical fatigue (β = .46), slower backward walking speed (β = −.41), slower processing speed (β = −.44), impaired task-switching (β = .32), higher anxiety (β = .38), and avoidance behavior (β = .58) predicted greater CAF. Hippocampal and cerebellar volumes were not significant predictors after accounting for disease severity. DFA classified participants with high accuracy (73.9% low CAF; 65.0% high CAF). Conclusion CAF in MS reflects a complex interplay of physical, cognitive, and emotional factors. While structural brain measures were not independently predictive, the combined influence of motor, cognitive, and psychological factors highlight the need for multidomain assessments and treatments to reduce CAF and its negative consequences in MS.
Takla et al. (2026) studied this question.