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Four‐Year Cognitive Outcomes in Multiple Sclerosis: Associations With Lesion Myelin Integrity

Year: 2026

Type: article

Abstract: OBJECTIVES: Cognitive impairment is prevalent in patients with multiple sclerosis (MS) but whether lesion myelin integrity influences future cognitive outcomes remains unclear. We investigated the relationship between baseline lesion myelin water fraction (MWF) and cognitive performance 4 years later. METHODS: We conducted a longitudinal study of 118 patients with MS. Cognitive function was evaluated annually for 5 years using the symbol digit modalities test (SDMT), California verbal learning test-II (CVLT-II) immediate recall, and brief visuospatial memory test-revised (BVMT-R). Lesion level MWF maps were the primary variable of interest, while paramagnetic rim lesions (PRLs) and structural imaging measures were included as covariates. We used a functional linear regression model with both scalar and functional covariates, followed by a stepwise variable selection procedure. RESULTS: After adjustment for baseline cognition and clinical covariates, participants with higher baseline lesion-level MWF values in the mid-range of the lesion distribution exhibited better SDMT at 4 years (p = 0.006). Greater heterogeneity in lesion-level MWF was associated with worse visuospatial memory performance on the BVMT-R at Year 4. Conversely, lesion MWF was not associated with CVLT-II performance. Additional covariates in the final models included PRLs and cortical thinning for SDMT, PRLs and disease duration for BVMT-R, and thalamic atrophy for CVLT-II. INTERPRETATION: Lesion myelin integrity was associated with future cognitive performance, particularly in domains of processing speed and visuospatial memory. These findings suggest that lesion demyelination contributes to cognitive outcomes in MS, which may provide a potential focus for future work improving risk stratification for cognitive impairment.

Source: Annals of Clinical and Translational Neurology

DOI: 10.1002/acn3.70577