Cortical lesions impact cognitive decline in multiple sclerosis via volume loss of nonlesional cortex
Abstract Objective To 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. Methods In this longitudinal study, 230 people with multiple sclerosis and 60 health...
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| Format: | Article |
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Wiley
2025-01-01
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| Series: | Annals of Clinical and Translational Neurology |
| Online Access: | https://doi.org/10.1002/acn3.52261 |
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| author | Eva A. Krijnen Maureen vanDam Albulena Bajrami Piet M. Bouman Samantha Noteboom Frederik Barkhof Bernard M.J. Uitdehaag Martijn D. Steenwijk Eric C. Klawiter Ismail Koubiyr Menno M. Schoonheim |
| author_facet | Eva A. Krijnen Maureen vanDam Albulena Bajrami Piet M. Bouman Samantha Noteboom Frederik Barkhof Bernard M.J. Uitdehaag Martijn D. Steenwijk Eric C. Klawiter Ismail Koubiyr Menno M. Schoonheim |
| author_sort | Eva A. Krijnen |
| collection | DOAJ |
| description | Abstract Objective To 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. Methods In 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. Results Prevalence 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. Interpretation Multiple 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. |
| format | Article |
| id | doaj-art-cc90a1c3e7644d11b04f024555912f27 |
| institution | Kabale University |
| issn | 2328-9503 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
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| series | Annals of Clinical and Translational Neurology |
| spelling | doaj-art-cc90a1c3e7644d11b04f024555912f272025-01-21T05:41:42ZengWileyAnnals of Clinical and Translational Neurology2328-95032025-01-0112112113610.1002/acn3.52261Cortical lesions impact cognitive decline in multiple sclerosis via volume loss of nonlesional cortexEva A. Krijnen0Maureen vanDam1Albulena Bajrami2Piet M. Bouman3Samantha Noteboom4Frederik Barkhof5Bernard M.J. Uitdehaag6Martijn D. Steenwijk7Eric C. Klawiter8Ismail Koubiyr9Menno M. Schoonheim10MS Center Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam The NetherlandsMS Center Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam The NetherlandsMS Center Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam The NetherlandsMS Center Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam The NetherlandsMS Center Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam The NetherlandsMS Center Amsterdam, Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam The NetherlandsMS Center Amsterdam, Department of Neurology, Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam The NetherlandsMS Center Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam The NetherlandsDepartment of Neurology Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USAMS Center Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam The NetherlandsMS Center Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam The NetherlandsAbstract Objective To 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. Methods In 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. Results Prevalence 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. Interpretation Multiple 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.https://doi.org/10.1002/acn3.52261 |
| spellingShingle | Eva A. Krijnen Maureen vanDam Albulena Bajrami Piet M. Bouman Samantha Noteboom Frederik Barkhof Bernard M.J. Uitdehaag Martijn D. Steenwijk Eric C. Klawiter Ismail Koubiyr Menno M. Schoonheim Cortical lesions impact cognitive decline in multiple sclerosis via volume loss of nonlesional cortex Annals of Clinical and Translational Neurology |
| title | Cortical lesions impact cognitive decline in multiple sclerosis via volume loss of nonlesional cortex |
| title_full | Cortical lesions impact cognitive decline in multiple sclerosis via volume loss of nonlesional cortex |
| title_fullStr | Cortical lesions impact cognitive decline in multiple sclerosis via volume loss of nonlesional cortex |
| title_full_unstemmed | Cortical lesions impact cognitive decline in multiple sclerosis via volume loss of nonlesional cortex |
| title_short | Cortical lesions impact cognitive decline in multiple sclerosis via volume loss of nonlesional cortex |
| title_sort | cortical lesions impact cognitive decline in multiple sclerosis via volume loss of nonlesional cortex |
| url | https://doi.org/10.1002/acn3.52261 |
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