ArticleAnnals of clinical and translational neurology2025
Cortical lesions impact cognitive decline in multiple sclerosis via volume loss of nonlesional cortex.
Article in Annals of clinical and translational neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Evaluation of cortical pathology in primary-progressive multiple sclerosis: a post hoc analysis of the SPRINT-MS trial.BMJ neurology open · 2026Article
- Soma and neurite density abnormalities of paramagnetic rim lesions and core-sign lesions in multiple sclerosis.Journal of neurology · 2025Article
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Authors and funding
11 authors.
Funding
Abstract
objectiveTo assess the interrelationship between cortical lesions and cortical thinning and volume loss in people with multiple sclerosis within cortical networks, and how this relates to future cognition.
methodsIn this longitudinal study, 230 people with multiple sclerosis and 60 healthy controls underwent 3 Tesla MRI at baseline and neuropsychological assessment at baseline and 5-year follow-up. Cortical regions (N = 212) were divided into seven functional networks. Regions were defined as either lesional or normal-appearing cortex based on presence of a cortical lesion on artificial intelligence-generated double inversion-recovery scans. Cortical volume and thickness were determined within lesional or normal-appearing cortex.
resultsPrevalence of at least one cortical lesion was highest in the limbic (73%) followed by the default mode network (70.9%). Multiple sclerosis-related cortical thinning was more pronounced in lesional (mean Z-score = 0.70 ± 0.84) compared to normal-appearing cortex (-0.45 ± 0.60; P < 0.001) in all, except sensorimotor, networks. Cognitive dysfunction, particularly of verbal memory, visuospatial memory, and inhibition, at follow-up was best predicted by baseline network volume of normal-appearing cortex of the default mode network [B (95% CI) = 0.31 (0.18; 0.43), P < 0.001]. Mediation analysis showed that the effect of cortical lesions on future cognition was mediated by volume loss of the normal-appearing instead of lesional cortex, independent of white matter lesion volume.
interpretationMultiple sclerosis-related cortical thinning was worse in lesional compared to normal-appearing cortex, while volume loss of normal-appearing cortex was most predictive of subsequent cognitive decline, particularly in the default mode network. Mediation analyses indicate that cortical lesions impact cognitive decline plausibly by inducing atrophy, rather than through a direct effect.
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