Four‐Year Cognitive Outcomes in Multiple Sclerosis: Associations With Lesion Myelin Integrity
5 affiliations
- 1Department of Neurology Weill Cornell Medicine New York New York USA
- 2Department of Psychiatry Weill Cornell Medicine New York New York USA
- 3Mathematics and Statistics Cleveland State University Cleveland Ohio USA
- 4Department of Radiology Weill Cornell Medicine New York New York USA
- 5Feil Family Brain and Mind Institute Weill Cornell Medicine New York New York USA
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.
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BibTeX
@article{pliskabloch2026fouryear,
title = {{Four‐Year Cognitive Outcomes in Multiple Sclerosis: Associations With Lesion Myelin Integrity}},
author = {Iliana Pliska‐Bloch and Hannah Schwartz and Kimberly H. Markowitz and Abhishek Jaywant and Christopher D. Hildenbrand and Jai Perumal and Ulrike W. Kaunzner and Thanh D. Nguyen and Sandra Hurtado Rúa and Susan A. Gauthier},
journal = {Annals of Clinical and Translational Neurology},
year = {2026},
month = nov,
doi = {10.1002/acn3.70577},
url = {https://doi.org/10.1002/acn3.70577},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Four‐Year Cognitive Outcomes in Multiple Sclerosis: Associations With Lesion Myelin Integrity
AU - Iliana Pliska‐Bloch
AU - Hannah Schwartz
AU - Kimberly H. Markowitz
AU - Abhishek Jaywant
AU - Christopher D. Hildenbrand
AU - Jai Perumal
AU - Ulrike W. Kaunzner
AU - Thanh D. Nguyen
AU - Sandra Hurtado Rúa
AU - Susan A. Gauthier
PY - 2026
DA - 2026/11/04
JO - Annals of Clinical and Translational Neurology
DO - 10.1002/acn3.70577
UR - https://doi.org/10.1002/acn3.70577
AB - 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.
SN - 2328-9503
ER -