Abstract
INTRODUCTION: Individuals with Down syndrome (DS) face a significant risk of neurodegeneration, and gait variability may serve as a clinical biomarker of neurological health. This longitudinal parent substudy aimed to explore relationships between gait, white matter (WM) integrity, and cognitive function in DS. METHODS: The associations were investigated between magnetic resonance imaging diffusion tensor imaging (DTI), cognition, and self-paced gait data from 22 DS participants (mean age ± SD 37 ± 7.5 years). RESULTS: DTI measures, such as lower fractional anisotropy (FA) and higher mean diffusivity, were correlated with greater step time variability but not normalized velocities. Lower cognitive scores on the Vineland Adaptive Behavior Composite, Dementia Questionnaire for People with Learning Disabilities, and Motor Skill subscale were correlated with FA. DISCUSSION: Gait variability correlates with WM integrity and cognitive function in DS, suggesting that gait and DTI measures may serve as clinical markers of neurological decline. HIGHLIGHTS: Gait variability linked to white matter integrity in individuals with Down syndrome (DS). Lower fractional anisotropy and higher mean diffusivity are associated with increased step time variability in DS. Cognitive decline is tied to white matter changes in motor-related brain regions. Gait analysis alongside diffusion tensor imaging may aid in screening for cognitive impairment in DS.