Multidomain Cognitive Decline and Motor Disability in Multiple Sclerosis: A Retrospective Cohort Study

Background: Multiple sclerosis (MS) is characterized by heterogeneous trajectories of motor and cognitive disability. This study aimed to characterize longitudinal cognitive and motor trajectories across MS phenotypes and to identify baseline predictors of subsequent worsening. Methods: This retrospective cohort included 68 adults with MS followed for approximately six years. Cognitive performance was assessed at baseline (T0) and follow-up (T1) using the Rao's Brief Repeatable Battery (BRB-N) and quantified using the Cognitive Impairment Index (CII). Clinical, demographic, neuropsychological, psychological, and neuroimaging variables were collected. Longitudinal cognitive changes were evaluated using linear mixed-effects models including baseline phenotype, time, and phenotype-by-time interaction. Logistic regression was used to investigate predictors of motor and cognitive worsening. Results: At baseline, 52.9% of patients met criteria for cognitive impairment. During follow-up, 50.0% experienced motor worsening and 77.9% experienced cognitive worsening; 44.1% met the study definition of cognitive progression independent of relapse activity. Memory CII increased significantly over time in the whole cohort (p = 0.003), whereas the phenotype-by-time interaction was not significant for Memory CII (p = 0.546), Executive CII (p = 0.211), or Total CII (p = 0.293). After Holm correction, the increase in Memory CII remained significant in baseline RRMS (+1.59; adjusted p = 0.007), but not in baseline SPMS (+1.40; adjusted p = 0.072) or PPMS (+0.57; adjusted p = 0.467). Eleven patients (32.4% of baseline RRMS) transitioned to SPMS and were retained in the baseline RRMS group for the primary longitudinal analyses. Their mean ΔEDSS was +1.91. Conclusions: Cognitive and motor progression represent partially distinct dimensions of MS evolution. Memory was the cognitive domain showing the clearest longitudinal worsening, particularly among patients classified as RRMS at baseline, while the magnitude of cognitive change did not differ significantly between baseline phenotypes.