The association between cognition and motor performance is beyond structural damage in relapsing–remitting multiple sclerosis

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Previous studies demonstrated an association between motor and cognitive performance in multiple sclerosis (MS). However, disease-related brain damage might represent a common substrate to both phenomena, which was not considered before. Aim of this study is to investigate whether the association between cognition and motor function is beyond structural damage in patients with MS. Eighty-one healthy controls and 106 relapsing-remitting (RR) MS patients underwent a 3.0T MRI with quantification of T2-lesion volumes, T1-lesion volumes and normalized brain volumes. A functional examination [Nine-Hole Peg Test (9-HPT), Timed 25-Foot Walk test (T25FW) and Expanded Disability Status Scale] and a neuropsychological evaluation (Brief Repeatable Battery of Neuropsychological Tests) were also administered. Association between demographic, clinical, cognitive, MRI and functional measures were analysed with univariate analyses and hierarchical linear regression. In RRMS patients, Spatial Recall Test and Symbol Digit Modalities Test were positively correlated with 9-HPT (p < 0.001) and T25FW (p ≤ 0.035); Paced Auditory Serial Addition Test (PASAT) correlated with 9-HPT (p ≤ 0.009). 9-HPT and T25FW were significantly associated with normalized brain volumes (p ≤ 0.016), T2- and T1-lesion volumes (p ≤ 0.009). Hierarchical regression models selected age and normalized deep gray matter volume as predictors of T25FW (adjusted-R2 = 0.109). Younger age, female sex, higher normalized gray matter volume and higher PASAT 2″ scores predicted higher 9-HPT scores (adjusted-R2 = 0.337). In RRMS patients, deficit in information processing speed and executive function may contribute to hand motor dysfunction beyond the effect of structural disease-related burden, supporting the integration of motor and cognitive assessment in clinical settings.