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 MS.
“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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“Both scales estimate vocabulary knowledge which is a commonly used indicator of intellectual enrichment [11], a proxy of CR.”
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“Preservation of cognitive function is also depended on intellectual enrichment such as educational achievement and the lifestyle of each individual [67].”
BackgroundSerra, L., Gelfo, F., Petrosini, L., Domenico, C. D., Bozzali, M., & Caltagirone, C. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180609 · Cited by 32 · see citing works
“In particular, in several studies [4, 34-41], cognitive, social and physical activities pursued continuatively and intensely during the entire lifespan have been recognised as factors reducing the risk of AD.”
Social support is linked to mental health, quality of life, and motor function in multiple sclerosis
Kever, A., Buyukturkoglu, K., Riley, C., Jager, P. L. D., & Leavitt, V. M. (2021) · Journal of Neurology · doi:10.1007/s00415-020-10330-7 · Cited by 37 · see citing works
Self-citationSundgren, M., Nikulin, V. V., Maurex, L., Wåhlin, Å., Piehl, F., & Brismar, T. (2014) · Clinical Neurophysiology · doi:10.1016/j.clinph.2014.07.024 · Cited by 33 · see citing works
“High premorbid intelligence has been proposed to be a moderating factor in ageing and AD (see Stern, 2009) and a similar protective effect has been reported in MS (see Sumowski and Leavitt, 2013).”
BackgroundCognition in multiple sclerosis: Between cognitive reserve and brain volume
Fenu, G., Lorefice, L., Arru, M., et al. (2018) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2018.01.011 · Cited by 33 · see citing works
Sumowski, J. F., Rocca, M. A., Leavitt, V. M., et al. (2016) · Multiple Sclerosis Journal · doi:10.1177/1352458516630822 · Cited by 30 · see citing works
“Note that patients endorsed the frequency with which each activity was performed during their early 20s as daily (5), several times per week (4), several times per month (3), several times per year (2), or once per year or less (1).”
BackgroundSelf-citationKrieger, S. C., & Sumowski, J. F. (2017) · Neurologic Clinics · doi:10.1016/j.ncl.2017.08.003 · Cited by 30 · see citing works
Self-citationEffect of cognitive reserve on cognitive function in Parkinson’s disease
Gu, L., & Xu, H. (2022) · Neurological Sciences · doi:10.1007/s10072-022-05985-1 · Cited by 29 · see citing works
“1 3 epidemiological evidence supported the presence of CR: educational level, leisure activities, and occupation level were confirmed to be associated with the risk of cognitive impairment in aging adults [4–6] and clinical changes in some neuropsychological disorders, such as PD [7], multiple sclerosis [8], stroke an…”
BackgroundTauhid, S., Chu, R., Sasané, R., et al. (2015) · Journal of Neurology · doi:10.1007/s00415-015-7853-x · Cited by 28 · see citing works
“Finally, the presence of cognitive reserve [35], which was not assessed in our study, may have provided adaptive ability for patients to maintain function, despite the accumulation of disease-related structural brain changes.”
BackgroundApathy in multiple sclerosis: gender matters
Novo, A. M., Batista, S., Tenente, J., et al. (2016) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2016.02.038 · Cited by 28 · see citing works
“The greater intellectual enrichment attenuates the negative effect of disease burden on cognitive and motivational status [25], and, theoretically, may have the same effect on neuropsychiatric manifestations as apathy.”
BackgroundCognitive and brain reserve in multiple sclerosis––A cross-sectional study
Ifantopoulou, P., Artemiadis, A., Bakirtzis, C., Zekiou, K., Papadopoulos, T.-S., Diakogiannis, I., Hadjigeorgiou, G. M., Grigoriadis, N., & Orologas, A. (2019) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2019.07.027 · Cited by 27 · see citing works
Functional and self-care capacity of people with multiple sclerosis
Oliveira, A. R. D. S., Bezutti, L. M., Silva, J. L. G., et al. (2019) · Revista Latino-Americana de Enfermagem · doi:10.1590/1518-8345.3068.3183 · Cited by 26 · see citing works
“We found in the literature that most patients are diagnosed at the beginning of adulthood, between 20 and 40 years of age, that the disease is twice as prevalent among women, and that higher educational level is protective against the cognitive function decline and disease overload(32-33).”
BackgroundPremorbid functional reserve modulates the effect of rehabilitation in multiple sclerosis
Castelli, L., Giglio, L. D., Haggiag, S., Traini, A., Luca, F. D., Ruggieri, S., & Prosperini, L. (2020) · Neurological Sciences · doi:10.1007/s10072-019-04237-z · Cited by 26 · see citing works
“Functional reserve seems to be mainly influenced by premorbid individual’s education, intellect, mental stimulation, participation in leisure activities, social engagement, physical activity, and even dietary factors [6].”
BackgroundSparring and Neurological Function in Professional Boxers
Stiller, J. W., Yu, S. S., Brenner, L. A., LANGENBERG, P. W., Scrofani, P., Pannella, P., Hsu, E. B., Roberts, D. W., Monsell, R. M. T., Binks, S. W., et al. (2014) · Frontiers in Public Health · doi:10.3389/fpubh.2014.00069 · Cited by 26 · see citing works
Validity and reliability of "Cognitive Reserve Index Questionnaire" for the Turkish Population.
Ozakbas, S., Yiğit, P., Akyuz, Z., Sagıcı, O., Abasıyanık, Z., Ozdogar, A. T., Kahraman, T., Bozan, H. R., & Hosgel, I. (2021) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2021.102817 · Cited by 23 · see citing works
Jin, J., Ko, I., Kim, S., Shin, M., Kim, S., & Jee, Y. (2014) · Journal of Exercise Rehabilitation · doi:10.12965/jer.140103 · Cited by 26 · see citing works
“…MS may express difficulty in short-term memory, prospective memory (making and keeping plans), adjusting to changing circumstances, multi-tasking, name-face recognition, managing mathematical tasks, and functioning in multi-stimuli environments (Sumowski and Leavitt, 2013; Thornton and Raz, 1997).”
BackgroundFriedová, L., Motýl, J., Srpová, B., Oechtering, J., Barro, C., Vodehnalová, K., Andělová, M., Nosková, L., Fialová, L., Havrdová, E., et al. (2020) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2020.102534 · Cited by 24 · see citing works
Schwartz, C. E., Michael, W., Zhang, J., Rapkin, B. D., & Sprangers, M. A. G. (2017) · Quality of Life Research · doi:10.1007/s11136-017-1694-2 · Cited by 23 · see citing works
López-Soley, E., Solana, E., Martínez‐Heras, E., Andorrà, M., Raduà, J., Prats‐Uribe, A., Montejo, C., Solà‐Valls, N., Sepúlveda, M., Pulido-Valdeolivas, I., et al. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.581700 · Cited by 22 · see citing works
“This clinicopathological dissociation (7) indicates that certain factors protect against cognitive decline, such as the cognitive reserve (CR), understood to be lifelong intellectual enrichment that attenuates the negative effect of MS disease burden on neuropsychological activity (8, 9).”
BackgroundDarviri, C., Zavitsanou, C., Delikou, A., Giotaki, A., Artemiadis, A., Anagnostouli, M. C., Varvogli, L., Vasdekis, S. N., & Chrousos, G. P. (2016) · Psychology · doi:10.4236/psych.2016.74059 · Cited by 21 · see citing works
“…Functional magnetic resonance imaging (fMRI) studies show several brain regions (such as the default-modenetwork, DMN), and the altered function of these regions denotes adequate cognitive reserve and compensation for the intellectual dysfunction (Bonavita et al., 2011; Sumowski & Leavitt, 2013).”
BackgroundDavenport, L., Cogley, C., Monaghan, R., Gaughan, M., Yap, M., Bramham, J., Tubridy, N. J., McGuigan, C., & O’Keeffe, F. M. (2022) · Journal of Neuropsychology · doi:10.1111/jnp.12283 · Cited by 20 · see citing works
Cognitive impairment in multiple sclerosis: “classic” knowledge and recent acquisitions
Piacentini, C., Argento, O., & Nocentini, U. (2023) · Arquivos de Neuro-Psiquiatria · doi:10.1055/s-0043-1763485 · Cited by 18 · see citing works
Cognitive and brain reserve for mind-body therapeutic approaches in multiple sclerosis: A review
Crescentini, C., Urgesi, C., Fabbro, F., & Eleopra, R. (2014) · Restorative Neurology and Neuroscience · doi:10.3233/rnn-130364 · Cited by 18 · see citing works
“Thus, CR and BR amoreupdatedandextensivereviewofthestudiesthat haveexploredCRandBRinpatientswithMS,relative 2011;SumowskiandLeavitt,2013)(seeTable1);and ii)todiscussmorethoroughlythanhithertotheimpli-cationsthatthesestudieshaveforthedevelopmentof onmind-bodymedicineforMSpatients.”
InfluentialRezaeimanesh, N., Rafiee, P., Saeedi, R., Khosravian, P., Sahraian, M. A., Eskandarieh, S., Moghadasi, A. N., & Jahromi, S. R. (2023) · BioMetals · doi:10.1007/s10534-023-00548-z · Cited by 17 · see citing works
“These conditions have the potential to significantly impede the attainment of typical objectives in early and mid-adulthood (Sumowski and Leavitt 2013).”
Sandry, J. D., Paxton, J. L., & Sumowski, J. F. (2016) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617715001307 · Cited by 17 · see citing works
“…also examine whether relationships between both education and intelligence (proxies of general ability) and PASAT performance are mediated through domain-specific knowledge (mathematical ability), which may present a domain-specific aspect of cognitive reserve (for review Sumowski & Leavitt, 2013).”
BackgroundSelf-citationBalloff, C., Penner, I., Ma, M., Georgiades, I., Scala, L., Troullinakis, N., Graf, J., Kremer, D., Aktas, O., Hartung, H., et al. (2022) · Brain Stimulation · doi:10.1016/j.brs.2022.02.007 · Cited by 17 · see citing works
“These results suggest that mechanisms of reserve only become relevant when a sufficient degree of pathology, that needs to be compensated, is present [52,53].”
BackgroundSantinelli, F. B., Veldkamp, R., Vitório, R. R., et al. (2024) · Neurorehabilitation and neural repair · doi:10.1177/15459683241279066 · Cited by 16 · see citing works
“Therefore, considering that pwMS have a lower neural reserve, 31 one might expect insufficient capacity to recruit neural resources and poorer task performance during DT compared to their healthy counterparts.”
Differential diagnosis, discerning depression from cognition
Portaccio, E. (2016) · Acta Neurologica Scandinavica · doi:10.1111/ane.12652 · Cited by 16 · see citing works
Martínez‐Ginés, M. L., García‐Domínguez, J. M., Forero, L., et al. (2018) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2018.04.003 · Cited by 16 · see citing works
Highlighting the Role of Cognitive and Brain Reserve in the Substance use Disorder Field
Cutuli, D., de Guevara-Miranda, D. L., Castilla-Ortega, E., Santín, L. J., & Sampedro-Piquero, P. (2019) · Current Neuropharmacology · doi:10.2174/1570159x17666190617100707 · Cited by 14 · see citing works
Update on Recent Developments in Communication and Swallowing in Multiple Sclerosis
Biagi, F. D., Heikkola, L. M., Nordio, S., et al. (2020) · International Journal of MS Care · doi:10.7224/1537-2073.2020-023 · Cited by 16 · see citing works
Tract-specific MRI measures explain learning and recall differences in multiple sclerosis
Winter, M., Tallantyre, E. C., Brice, T. A. W., Robertson, N. P., Jones, D. K., & Chamberland, M. (2021) · Brain Communications · doi:10.1093/braincomms/fcab065 · Cited by 15 · see citing works
Cognitive reserve as a moderating factor between EDSS and cognition in multiple sclerosis
Tremblay, A., Charest, K., Brando, E., Roger, É., Duquette, P., & Rouleau, I. (2022) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2022.104482 · Cited by 16 · see citing works
Bizzo, B. C., Sanchez, T. A., Tobyne, S. M., Bireley, J. D., Lev, M. H., Gasparetto, E. L., & Klawiter, E. C. (2020) · Journal of Neuroimaging · doi:10.1111/jon.12779 · Cited by 16 · see citing works
“structural brain diseases (eg, prior stroke); (3) severe depression as rated by scoring >28 on the Beck Depression Inventory; (4) other psychiatric diseases meeting Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria bipolar disorder, obsessive compulsive disorder, or schizophrenia; and (5) seve…”
BackgroundMigliore, S., D’Aurizio, G., Scaricamazza, E., Maffi, S., Ceccarelli, C., Ristori, G., Romano, S., Castaldo, A., Fichera, M., Curcio, G., et al. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12010036 · Cited by 15 · see citing works
“The CR hypothesis has been well-supported by studies involving various neurological conditions, such as Alzheimer’s disease (AD) [12], Parkinson’s disease (PD) [13], Multiple Sclerosis (MS) [14], stroke [15], traumatic brain injury [16], and age-related white matter ischemic changes [17].”
MethodLiu, Y., Liu, Y., Yip, P., Meguro, M., & Meguro, K. (2017) · Psychogeriatrics · doi:10.1111/psyg.12230 · Cited by 15 · see citing works
Covey, T. J., Golan, D., Doniger, G. M., Sergott, R. C., Zarif, M., Bumstead, B., Buhse, M., Kaczmarek, O., Mebrahtu, S., Bergmann, C., et al. (2021) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2021.103349 · Cited by 13 · see citing works
Jeffery, D., di Cantogno, E. V., Ritter, S., Meier, D. P., Radue, E. W., & Camu, W. (2015) · Journal of Neurology · doi:10.1007/s00415-015-7959-1 · Cited by 13 · see citing works
Cognitive dysfunction in systemic lupus erythematosus: how do we advance our understanding?
Raghunath, S., Glikmann‐Johnston, Y., Hanly, J. G., Morand, E. F., Stout, J. C., & Hoi, A. Y.-B. (2022) · The Lancet Rheumatology · doi:10.1016/s2665-9913(21)00331-3 · Cited by 13 · see citing works
Skorve, E., Lundervold, A. J., Torkildsen, Ø., et al. (2022) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2022.104398 · Cited by 12 · see citing works
Longitudinal Stability of Cognition in Early-Phase Relapsing-Remitting Multiple Sclerosis
Barbu, R. M., Berard, J. A., Gresham, L. M., & Walker, L. A. S. (2017) · International Journal of MS Care · doi:10.7224/1537-2073.2016-073 · Cited by 12 · see citing works
Cognitive Relapse in Multiple Sclerosis: New Findings and Directions for Future Research
Weinstock, Z. L., & Benedict, R. H. B. (2022) · NeuroSci · doi:10.3390/neurosci3030036 · Cited by 11 · see citing works
“Although cognitive reserve is most commonly conceptualized as a gradually adaptive process [50], it remains to be seen whether and how it might interact with acute cognitive change during MS relapse.”
BackgroundMultiple brain networks support processing speed abilities of patients with multiple sclerosis
Manca, R., Mitolo, M., Stabile, M. R., Bevilacqua, F., Sharrack, B., & Venneri, A. (2019) · Postgraduate Medicine · doi:10.1080/00325481.2019.1663706 · Cited by 11 · see citing works
“Similarly, education and total intracranial volume were included in the analyses to account for possible effects of cognitive [46] and brain reserve [5,47].”
Iancheva, D., Trenova, A. G., Mantarova, S., & Terziyski, K. V. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00754 · Cited by 11 · see citing works
“Maximal lifetime brain growth (MLBG) is considered a main heritable factor (15).”
BackgroundHuynh, T. L. T., Silveira, S. L., & Motl, R. W. (2021) · Disability and Rehabilitation · doi:10.1080/09638288.2021.1954705 · Cited by 11 · see citing works
Kalron, A. (2016) · International Journal of Rehabilitation Research · doi:10.1097/mrr.0000000000000177 · Cited by 10 · see citing works
“Cognitive reserve declines with MS disease progression (Sumowski and Leavitt, 2013; DeLuca et al., 2015).”
BackgroundBaumeister, T. R., Lin, S., Vavasour, I. M., Kolind, S., Kosaka, B., Li, D. K. B., Traboulsee, A. L., MacKay, A. L., & McKeown, M. J. (2019) · NeuroImage Clinical · doi:10.1016/j.nicl.2019.101926 · Cited by 10 · see citing works
“In the theory of cognitive reserve (Stern, 2002; Sumowski and Leavitt, 2013; Tucker-Drob et al., 2011), higher levels of education may alter synaptic organization and/or neuronal networks so individuals can still sustain damage and maintain adequate cognitive function (Stern, 2002).”
van Munster, C. E. P., Burggraaff, J., Steinheimer, S., et al. (2023) · International Journal of MS Care · doi:10.7224/1537-2073.2021-069 · Cited by 9 · see citing works
Foreman, L. M., Child, B., Saywell, I., Collins‐Praino, L. E., & Baetu, I. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106067 · Cited by 10 · see citing works
“…against the cognitive effects of Alzheimer ’ s disease (Lee et al., 2022), Parkinson ’ s disease (Guzzetti et al., 2019), multiple sclerosis (Sumowski and Leavitt, 2013), HIV-related dementia (Kaur et al., 2020), stroke (Rosenich et al., 2020) and traumatic brain injury (Stenberg et al.,…”
Coll, C., Quintana, E., Buxó, M., et al. (2022) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2022.104397 · Cited by 9 · see citing works
Patterns of attention deficit in relapsing and progressive phenotypes of multiple sclerosis
Tabibian, F., Azimzadeh, K., Shaygannejad, V., Ashtari, F., Adibi, I., & Sanayei, M. (2023) · Scientific Reports · doi:10.1038/s41598-023-40327-x · Cited by 9 · see citing works
“However, when brain damages are too great, as in progressive forms of disease, this compensatory response may be insufficient and the inhibitory effect of fatigue prevails 57 .”
BackgroundCognitive reserve: the evolution of the conceptual framework
Serra, L., Caltagirone, C., & Bozzali, M. (2017) · Journal of Systems and Integrative Neuroscience · doi:10.15761/jsin.1000159 · Cited by 9 · see citing works
“), volunteering, entertaining friends or relatives [5,25,27,28].”
Özkul, Ç., Guclu‐Gunduz, A., Eldemir, K., Apaydın, Y., Yazıcı, G., & İrkeç, C. (2020) · International Journal of Rehabilitation Research · doi:10.1097/mrr.0000000000000428 · Cited by 9 · see citing works
“It is known that education has a major contribution to cognitive reserve, which reduces the effects of both age-related and disease-related cognitive impairment (Sumowski and Leavitt, 2013).”
BackgroundAlirezaei, M., Forouzannia, S. M., Yarahmadi, P., et al. (2021) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2021.102758 · Cited by 9 · see citing works
Broche‐Pérez, Y., Jiménez-Morales, R. M., Monasterio-Ramos, L. O., & Bauer, J. J. (2024) · Neurología · doi:10.1016/j.nrl.2023.03.008 · Cited by 7 · see citing works
Szekely-Kohn, A. C., Castellani, M., Espino, D. M., Baronti, L., Ahmed, Z., Manifold, W. G. K., & Douglas, M. (2025) · Royal Society Open Science · doi:10.1098/rsos.241052 · Cited by 10 · see citing works
- 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 › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › 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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