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Cognitive reserve in multiple sclerosis
Open accessAbstract
Cognitive impairment is common among persons with multiple sclerosis (MS), but some patients are able to withstand considerable disease burden (e.g. white matter lesions, cerebral atrophy) without cognitive impairment (cognitive inefficiency, memory decline). What protects these patients from cognitive impairment? We review the literature on cognitive reserve in MS, which shows that heritable (larger maximal lifetime brain growth) and environmental (greater intellectual enrichment) factors attenuate the negative effect of disease burden on cognitive status. That is, persons with larger maximal lifetime brain growth, greater vocabulary knowledge, and/or greater early life participation in cognitive leisure activities (e.g. reading, hobbies) are better able to cope with MS disease without cognitive impairment. We review evidence that benefits of intellectual enrichment on cognitive status may stem from more efficient patterns of brain function. We discuss clinical implications and highlight important unanswered questions for future research on reserve against cognitive impairment in MS.
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“This finding is somewhat consistent with previous findings supporting the cognitive reserve hypothesis, that higher education mitigates cognitive problems associated with MS73–75.”
From Ecological momentary assessment of pain, fatigue, depressive, and cognitive symptoms reveals significant daily variability in multiple sclerosis (2017) · cites this paper as [74]
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Tazza, F., Schiavi, S., Leveraro, E., Cellerino, M., Boffa, G., Ballerini, S., Dighero, M., Uccelli, A., Sbragia, E., Aluan, K., et al. (2023) · Multiple Sclerosis Journal · doi:10.1177/13524585231217918 · Cited by 7
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Freedman, D., Campbell, K., & Feinstein, A. (2025) · Multiple Sclerosis Journal · doi:10.1177/13524585251383381 · Cited by 6
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Santos, T., Pinheiro, J., & Barros, P. (2015) · European Neurological Review · doi:10.17925/enr.2015.10.02.157 · Cited by 6
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ResultEmotionserkennung, Theory of Mind und Empathie bei Multipler Sklerose
Ayache, S. S., Chalah, M. A., Kümpfel, T., Padberg, F., Lefaucheur, J., & Palm, U. (2017) · Fortschritte der Neurologie · Psychiatrie · doi:10.1055/s-0043-118846 · Cited by 5
Multiparity in women with multiple sclerosis causes less long-term disability: Yes
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BackgroundCompensatory mechanisms amidst demyelinating disorders: insights into cognitive preservation
Dahhan, N. Z. A., Tseng, J., de Medeiros, C. B., Narayanan, S., Arnold, D. L., Coe, B. C., Munoz, D. P., Yeh, E. A., & Mabbott, D. (2024) · Brain Communications · doi:10.1093/braincomms/fcae353 · Cited by 6
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“Therefore, randomized controlled trials (RCTs) conducted with better methodology are clearly needed to ascertain the utility of cognitive rehabilitation in MS.”
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Santivasci, C. A., Mirmosayyeb, O., Jaworski, M. G., Balconi, J., Woodbeck, M., Bergsland, N., Zivadinov, R., Dwyer, M. G., Weinstock‐Guttman, B., & Benedict, R. H. B. (2025) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2025.106559 · Cited by 3
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“…“clinical–radiological paradox” describes the imperfect correlation between radiological findings and clinical symptoms (Rocca et al., 2015; Sumowski and Leavitt, 2013), cognitive dysfunction is frequently observed in MS subjects, affecting multiple domains such as attention, information…”
French consensus procedure for neuropsychological assessment in multiple sclerosis
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Dementia in Multiple Sclerosis
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Self-citationRegular monitoring of cognitive functions in multiple sclerosis
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Lesion‐Based Disconnectome Explains Cognitive Outcomes in Multiple Sclerosis
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“…the accumulation of cognitive reserve (Sumowski et al., 2009 ), which can be achieved through stimulating experiences such as the engagement in cognitive leisure activities, and educational and occupational attainment (Benedict et al., 2010 ; Sumowski et al., 2010 ; Sumowski & Leavitt, 2013 ).”
Neuropsychological Functions and Cognitive Neurorehabilitation in Multiple Sclerosis
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“One possible explanation for this protective mechanism is the brain reserve hypothesis and the cognitive reserve theory [36].”
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“PwMS with a high cognitive reserve can better cope with MS disease (Sumowski & Leavitt, 2013).”
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“In MS, years of education and pre-morbid intelligence (estimated based on reading ability, a skill less susceptible to pathology) have been found to be significant predictors of cognitive decline [3].”
BackgroundThe public health environment and brain function
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“…despite the presence of neuropathological changes associated with dementia (Stern 2012), Alzheimer’s disease (Scarmeas et al. 2003), Parkinson’s disease (Hindle et al. 2014), multiple sclerosis (Benedict et al. 2010; Sumowski and Leavitt 2013), and traumatic brain injury (Kesler et al. 2003).”
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“Nearly half of the pwMS experience cognitive impairment or thinking problems in higher levels of brain functions (Sumowski & Leavitt, 2013 ; Macías Islas & Ciampi, 2019).”
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“…time, a high CR seems to be associated with greater efficiency in brain functioning in PwMS, mainly in terms of the functional connectivity preserved despite the atrophy of the grey matter [17] and lower intensity of the activation of some areas, including the dorsolateral prefrontal cortex [8].”
BackgroundPediatric multiple sclerosis and acute disseminated encephalomyelitis
O’Neill, K. A., Fernandez-Carbonell, C., Maletić‐Savatić, M., & Krupp, L. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23947-2.00073-4
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Pavlovic, J., Sretenović, I., & Nedović, G. M. (2025) · Journal Human Research in Rehabilitation · doi:10.21554/hrr.042510
“An growing number of research have led to MS being seen through the lens of the CR theory, demonstrating that a higher CR reduces the deleterious impact of disease load on the cognitive status of patients with MS (Sumowski & Leavitt, 2013).”
Brissart, H., Joly, H., Castro, C., & Lenne, B. (2025) · Sclerosis · doi:10.3390/sclerosis3020014
“These techniques are developed on the hypothesis of an increase in brain plasticity capacities and the exploitation of cognitive reserve in these patients, to counter the long-term effects of the evolution of the pathophysiological process inherent in MS [22].”
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“As noted by Sumowski and Leavitt (2013), previous research in MS has found only a modest association between disease burden (e.g., lesion volume, cerebral atrophy) and level of cognitive impairment (Benedict, Bruce, et al., 2006; Deloire et al., 2011; Sumowski, 2015; Sumowski & Leavitt, 2013).”
InfluentialBroche‐Pérez, Y., Jiménez-Morales, R. M., Monasterio-Ramos, L. O., & Bauer, J. J. (2025) · Neurología (English Edition) · doi:10.1016/j.nrleng.2025.09.009
Functional Connectivity Alterations and Cognitive Impairment in Multiple Sclerosis
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COGNITIVE FUNCTIONS, POSTURAL CONTROL AND GAIT IN MULTIPLE SCLEROSIS: REVİEW
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Cognitive reserve and its contribution to predicting cognitive performance in multiple sclerosis
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“The reserve theory was developed to explain this variability, suggesting that genetic and environmental factors accumulated throughout an individual’s life can modulate the cognitive outcomes of neurological damage [10, 11].”
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“…effect only against the accrual of neurological disability and of brain atrophy, as previously observed, 61 while other factors like cognitive reserve and its proxies (premorbid intelligence quotient, leisure activities and education) 62 need to be considered while looking at cognitive performance.”
Badie, G., Ouattara, Y., Disseka, P. V., et al. (2026) · Central African Journal of Public Health · doi:10.11648/j.cajph.20261203.13
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Functional and Structural Imaging Features of Cognitive Profiles in Multiple Sclerosis
Jain, K., Valsasina, P., Mistri, D., et al. (2026) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000200669
“33 The second phenotype, MSD-VF, represented the smallest (10”
Mirmosayyeb, O., Panah, M. Y., Firouzabadi, S. R., Mohammadi, I., Alinejadfard, M., Vaheb, S., Shaygannejad, V., & Ghaffary, E. M. (2026) · Neuropsychology Review · doi:10.1007/s11065-026-09706-9
Metadata
- Authors
- Sumowski, J. F., & Leavitt, V. M.
- Affiliations
- Kessler Foundation (US)
- Venue
- Multiple Sclerosis Journal
- Publisher
- SAGE Publications
- Published
- 2013-07-29
- Volume
- 19
- Issue
- 9
- Pages
- 1122-1127
- ISSN
- 1352-4585 (ISSN-L)
- 1477-0970
- OpenAlex
- W2095723566
- Semantic Scholar
- 432cbdd4a7e844d9d6371ed10495dc761a5a0d88
- Cited by
- 185
- References
- 35
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 12 · 2023: 17 · 2022: 13 · 2021: 12 · 2020: 15 · 2019: 13 · 2018: 11 · 2017: 17 · 2016: 17 · 2015: 19 · 2014: 11 · 2013: 1
- FWCI
- 2.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Multiple Sclerosis Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Oncology › Cancer-related cognitive impairment studies
- Keywords
- cognitive reserve, multiple sclerosis, cognitive impairment, vocabulary, disease burden, white matter lesions, brain atrophy
- MeSH terms
- Cognition Disorders, Humans, Multiple Sclerosis, Cognitive Reserve
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