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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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Krieger, S. C., Cook, K., Nino, S. D., & Fletcher, M. (2016) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000000279 · Cited by 154
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“A potential influence of formal education on cognition in MS is frequently discussed within the framework of cognitive reserve or intellectual enrichment, referring to functional compensation of CI despite structural brain damage (Sumowski and Leavitt, 2013).”
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“…processes (i.e genetics, nutrition, physical health) and levels of environmental enrichment (i.e parenting, education, professional and leisure activities), is an important moderator of relationship between cognitive decline and brain pathology in MS (DeLuca et al 2015; Sumowski and Leavitt, 2013).”
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Mattioli, F., Bellomi, F., Stampatori, C., Capra, R., & Miniussi, C. (2016) · Multiple Sclerosis Journal · doi:10.1177/1352458515587597 · Cited by 87
Deficits in Social Cognition: An Unveiled Signature of Multiple Sclerosis
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“This could apply to MS patients in a way that those with higher cognitive reserve might experience less social cognitive deficits than others with similar extent of brain lesions (Sumowski et al., 2009; Sumowski & Leavitt, 2013).”
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Serra, L., Musicco, M., Cercignani, M., Torso, M., Spanò, B., Mastropasqua, C., Giulietti, G., Marra, C., Bruno, G., Koch, G., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.10.010 · Cited by 60
“The questionnaire is an Italian translation of the questionnaire developed by Sumowski et al. (2010) who used it in a cohort of patients with multiple sclerosis, demonstrating that patients who engaged in more cognitive leisure activities were able to withstand more severe brain atrophy at a given cognitive status.”
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Cognitive Reserve as a Useful Concept for Early Intervention Research in Multiple Sclerosis
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“(14)], showing that MS patients with greater education (24–27) and literacy/vocabulary (estimatedwith vocabulary) (28–31) are protected against diseaserelated cognitive inefficiency and memory problems.”
BackgroundSelf-citationRecommendations on Social Determinants of Health in Neurologic Disease
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Cognitive reserve, cognition, and regional brain damage in MS: A 2 -year longitudinal study
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“In fact, in all the analyses, better cognitive performance was associated with higher cognitive reserve—expressed as premorbid IQ—which confirms the findings of other studies [36,37].”
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Longitudinal MRI and neuropsychological assessment of patients with clinically isolated syndrome
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“It is hypothesized that both heritable and environmental factors contribute to the reserve against MS-related cognitive deterioration [39, 41].”
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“This dissociation may be explained by variability of cognitive performance among patients with CIS, where a cognitive reserve and a positive effect of interferon-beta on cognition may play an important role [55, 56].”
Dynamic Assessment of Social Cognition in Individuals with Multiple Sclerosis: A Pilot Study
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“The role of cognitive reserve in protecting against cognitive dysfunction is well-known (Sumowski & Leavitt, 2013); however, it has not been explored in the realm of social cognition.”
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“ERPs did not perfectly predict cognitive performance, yet it is noteworthy that the ERPs during visual 2-stimulus oddball task were nearly as predictive as a model including only demographic and psychiatric factors, that have been shown to predict cognitive performance previously (e.g. Amato et al. 2013; Sumowski et a…”
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“It has been shown that both heritable (brain reserve) and environmental (greater intellectual enrichment) factors may attenuate the negative effects of MS on cognitive status in adults [12].”
Measurement and maintenance of reserve in multiple sclerosis
Sandroff, B. M., Schwartz, C. E., & DeLuca, J. (2016) · Journal of Neurology · doi:10.1007/s00415-016-8104-5 · Cited by 39
Symptom Management and Lifestyle Modifications in Multiple Sclerosis
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“In MS, intellectual enrichment is associated with functional brain circuit changes, including greater brain default network activation and less need for task-active cortical recruitment.(30) This MS cognitive reserve model modulates the effect of brain disease burden on cognitive loss.”
BackgroundDoes cognitive reserve play any role in multiple sclerosis? A meta-analytic study
Santangelo, G., Altieri, M., Gallo, A., & Trojano, L. (2019) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2019.02.017 · Cited by 39
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“Both scales estimate vocabulary knowledge which is a commonly used indicator of intellectual enrichment [11], a proxy of CR.”
BackgroundThe cognitive reserve theory in the setting of pediatric-onset multiple sclerosis
Pastò, L., Portaccio, E., Goretti, B., Ghezzi, A., Lori, S., Hakiki, B., Giannini, M., Righini, I., Razzolini, L., Niccolai, C., et al. (2016) · Multiple Sclerosis Journal · doi:10.1177/1352458516629559 · Cited by 35
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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].”
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“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
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“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
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“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).”
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Self-citationEffect of cognitive reserve on cognitive function in Parkinson’s disease
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“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…”
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“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
“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
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Oliveira, A. R. D. S., Bezutti, L. M., Silva, J. L. G., & Gasparino, R. C. (2019) · Revista Latino-Americana de Enfermagem · doi:10.1590/1518-8345.3068.3183 · Cited by 36
“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
“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 31
Validity and reliability of "Cognitive Reserve Index Questionnaire" for the Turkish Population.
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“…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
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“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 23
“…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
Cognitive impairment in multiple sclerosis: “classic” knowledge and recent acquisitions
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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 19
“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
“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
“…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., Aktaş, O., Hartung, H., et al. (2022) · Brain stimulation · doi:10.1016/j.brs.2022.02.007 · Cited by 17
“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., Kos, D., Vos, M., Nijssen, R., DeLuca, J., Ramari, C., & Feys, P. (2024) · Neurorehabilitation and neural repair · doi:10.1177/15459683241279066 · Cited by 18
“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 18
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
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
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
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
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
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
“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
“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
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
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
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 14
Skorve, E., Lundervold, A. J., Torkildsen, Ø., Riemer, F., Grüner, R., & Myhr, K. (2022) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2022.104398 · Cited by 13
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
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
“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 12
“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 12
“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
Kalron, A. (2016) · International Journal of Rehabilitation Research · doi:10.1097/mrr.0000000000000177 · Cited by 10
“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
“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
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 12
“…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
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 11
“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
“), 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
“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., Sahraian, M. A., Owji, M., Bidadian, M., Ghadiri, F., & Moghadasi, A. N. (2021) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2021.102758 · Cited by 10
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
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 12
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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