Do Secondary Progressive Multiple Sclerosis patients benefit from computer- based cognitive neurorehabilitation? A randomized sham controlled trial
Abstract
Background Cognitive impairment is common in multiple sclerosis (MS), but deficits tend to be more pronounced in progressive MS, negatively impacting daily functional capacity. Despite this, most cognitive rehabilitation (CR) interventions to date have focused on relapsing-remitting MS (RRMS). Moreover, information on the efficacy of CR in progressive MS is limited and controversial. The present study investigated the efficacy of a home based, computer assisted cognitive rehabilitation (HBCACR) intervention (RehaCom TM software) exclusively in a Secondary Progressive Multiple Sclerosis (SPMS) sample.Methods This was a randomized, multi site, sham controlled trial. Thirty six (36) individuals with SPMS, naïve to the RehaCom software, with cognitive deficits were randomized to the treatment (IG; n= 19) or control group condition (CG; n=17). Treatment with the RehaCom modules consisted of 24 domain and task specific, 45 minute session's over an 8-week period, three sessions per week, applied by each patient at home. The CG completed non specific computer based activities at home with the same frequency and duration. Primary cognitive outcome measures included the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery, and secondary outcome measures for depression (BDI-FS), fatigue (MFIS), and quality of life (EuroQol EQ-5D) visual analogue scale (VAS).Results The two groups were well matched on demographic and clinical characteristics, cognitive reserve and severity of cognitive deficits at baseline assessment. At post treatment assessment the IG group showed significant improvements with large effect sizes; in verbal learning [z = -4.759, p <.0005, g = 2.898], visuospatial memory [z = -3.940, p <.0005, g = 1.699] and information processing speed [z= -4.792, p <.0005, g = 2.980], compared with the sham control group. We also found significant between group differences on physical [z=-3.308, p = .001, g= -.604], cognitive [z = -4.011, p <.0005, g = -1.654], psychosocial [z= 3.308, p = .010, g = -.940], and general fatigue impact [z= -2.623, p = .008, g = -.519], depression severity [z = -2.730, p = .006, g = -.519], and quality of life [z= -4.239, p <.0005, g = -1.885] in favor of the treated group.Conclusion These data provide the first evidence supporting the efficacy of computer based restorative cognitive rehabilitation applied at home exclusively in SPMS patients, suggesting that adaptive neuroplasticity may occur after functional cognitive training in progressive MS. Improved cognitive functioning in combination with mood augmentation appear to have ameliorated fatigue, which impacted daily functioning activity and culminated in improved health related quality of life.
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There is preliminary evidence of the effectiveness of a computer-based cognitive neurorehabilitation for people with SPMS.
“There is some preliminary evidence showing the need expressed by people with SPMS for psychological support and a personalised care plan (60), as well as some preliminary evidence of the effectiveness of a computer-based cognitive neurorehabilitation (61).”
From Key demographics and psychological skills associated with adjustment to progressive Multiple Sclerosis early in the diagnosis (2022) · cites this paper as [61]
Cites
Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria
Polman, C. H., Reingold, S. C., Banwell, B., Clanet, M., Cohen, J. A., Filippi, M., Fujihara, K., Havrdova, E., Hutchinson, M., Kappos, L., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22366 · Cited by 9,802 · see citing works
Borenstein, M., Hedges, L. V., Higgins, J. P. T., & Rothstein, H. R. (2021) · doi:10.1002/9781119558378 · Cited by 9,799 · see citing works
Wechsler Abbreviated Scale of Intelligence
Dumont, R., Willis, J. O., Veizel, K., & Zibulsky, J. (2014) · Wiley eBooks · doi:10.1002/9781118660584.ese2519 · Cited by 5,547 · see citing works
Cognitive impairment in multiple sclerosis
Chiaravalloti, N. D., & DeLuca, J. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70259-x · Cited by 2,088 · see citing works
California Verbal Learning Test
Delis, D. C., Freeland, J., Kramer, J. H., & Kaplan, E. (1987) · PsycTESTS Dataset · doi:10.1037/t48844-000 · Cited by 1,450 · see citing works
Jones, H. E. (2010) · Paediatric and Perinatal Epidemiology · doi:10.1111/j.1365-3016.2010.01108.x · Cited by 1,447 · see citing works
Cognitive Reserve Index questionnaire (CRIq): a new instrument for measuring cognitive reserve
Nucci, M., Mapelli, D., & Mondini, S. (2012) · Aging Clinical and Experimental Research · doi:10.1007/bf03654795 · Cited by 699 · see citing works
California Verbal Learning Test
Templeton, D. M., Schwenk, M., & Duffus, J. H. (2016) · IUPAC Standards Online · doi:10.1515/iupac.87.0120 · Cited by 693 · see citing works
Cognitive Reserve Index questionnaire (CRIq): a new instrument for measuring cognitive reserve
Nucci, M., Mapelli, D., & Mondini, S. (2013) · Aging Clinical and Experimental Research · doi:10.3275/7800 · Cited by 549 · see citing works
Cognition in multiple sclerosis
Langdon, D. W. (2011) · Current Opinion in Neurology · doi:10.1097/wco.0b013e328346a43b · Cited by 403 · see citing works
Validity of the Beck Depression Inventory-Fast Screen in multiple sclerosis
Benedict, R. H. B., Fishman, I., McClellan, M., Bakshi, R., & Weinstock‐Guttman, B. (2003) · Multiple Sclerosis Journal · doi:10.1191/1352458503ms902oa · Cited by 336 · see citing works
Evolving concepts in the treatment of relapsing multiple sclerosis
Comi, G., Radaelli, M., & Sørensen, P. S. (2016) · The Lancet · doi:10.1016/s0140-6736(16)32388-1 · Cited by 309 · see citing works
Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function
Ontaneda, D., Thompson, A. J., Fox, R. J., & Cohen, J. A. (2017) · The Lancet · doi:10.1016/s0140-6736(16)31320-4 · Cited by 298 · see citing works
Filippi, M., Riccitelli, G. C., Mattioli, F., Capra, R., Stampatori, C., Pagani, E., Valsasina, P., Copetti, M., Falini, A., Comı, G., et al. (2012) · Radiology · doi:10.1148/radiol.11111299 · Cited by 219 · see citing works
Neuropsychological rehabilitation for multiple sclerosis
Rosti-Otajärvi, E. M., & Hämäläinen, P. I. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009131.pub3 · Cited by 217 · see citing works
Effects of exercise on fitness and cognition in progressive MS: a randomized, controlled pilot trial
Briken, S., Gold, S. M., Patra, S., Vettorazzi, E., Harbs, D., Tallner, A., Ketels, G., Schulz, K., & Heesen, C. (2013) · Multiple Sclerosis Journal · doi:10.1177/1352458513507358 · Cited by 209 · see citing works
Charvet, L. E., Yang, J., Shaw, M., Sherman, K., Haider, L., Xu, J., & Krupp, L. (2017) · PLoS ONE · doi:10.1371/journal.pone.0177177 · Cited by 205 · see citing works
Cognitive Impairment in Multiple Sclerosis With Regards to Disease Duration and Clinical Phenotypes
Brochet, B., & Ruet, A. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00261 · Cited by 191 · see citing works
Cognitive reserve in multiple sclerosis
Sumowski, J. F., & Leavitt, V. M. (2013) · Multiple Sclerosis Journal · doi:10.1177/1352458513498834 · Cited by 185 · see citing works
Mattioli, F., Stampatori, C., Zanotti, D., Parrinello, G., & Capra, R. (2009) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2009.09.024 · Cited by 176 · see citing works
Validity of the EuroQoL (EQ-5D) Instrument in a Greek General Population
Kontodimopoulos, N., Pappa, E., Niakas, D. A., Yfantopoulos, J., Dimitrakaki, C., & Tountas, Y. (2008) · Value in Health · doi:10.1111/j.1524-4733.2008.00356.x · Cited by 169 · see citing works
An RCT to treat learning impairment in multiple sclerosis
Chiaravalloti, N. D., Moore, N. B., Nikelshpur, O. M., & DeLuca, J. (2013) · Neurology · doi:10.1212/01.wnl.0000437295.97946.a8 · Cited by 167 · see citing works
Computer-Assisted Cognitive Rehabilitation of Attention Deficits for Multiple Sclerosis
Cerasa, A., Gioia, M. C., Valentino, P., Nisticò, R., Chiriaco, C., Pirritano, D., Tomaiuolo, F., Mangone, G., Trotta, M., Tallarico, T., et al. (2012) · Neurorehabilitation and neural repair · doi:10.1177/1545968312465194 · Cited by 153 · see citing works
Cognitive rehabilitation in multiple sclerosis: a systematic review
Mitolo, M., Venneri, A., Wilkinson, I. D., & Sharrack, B. (2015) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2015.05.004 · Cited by 136 · see citing works
Vogt, A., Kappos, L., Calabrese, P., Stöcklin, M., Gschwind, L., Opwis, K., & Penner, I. (2009) · Restorative Neurology and Neuroscience · doi:10.3233/rnn-2009-0473 · Cited by 134 · see citing works
Benedict, R. H. B., Smerbeck, A. M., Parikh, R. S., Rodgers, J. D., Cadavid, D., & Erlanger, D. M. (2012) · Multiple Sclerosis Journal · doi:10.1177/1352458511435717 · Cited by 130 · see citing works
Bonavita, S., Sacco, R., Corte, M. D., Esposito, S., Sparaco, M., d’Ambrosio, A., Docimo, R., Bisecco, A., Lavorgna, L., Corbo, D., et al. (2014) · Journal of Neurology · doi:10.1007/s00415-014-7528-z · Cited by 115 · see citing works
Chan, D., Binks, S. N. M., Nicholas, J. M., Frost, C. D., Cardoso, M. J., Sebastien Ourselin, A., Wilkie, D., Nicholas, R. S., & Chataway, J. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30113-8 · Cited by 112 · see citing works
Sastre‐Garriga, J., Alonso, J., Renom, M., Arévalo, M. J., González, I., Galán, I., Montalbán, X., & Rovira, À. (2010) · Multiple Sclerosis Journal · doi:10.1177/1352458510389219 · Cited by 110 · see citing works
Cognitive Rehabilitation in Multiple Sclerosis: The Role of Plasticity
Chiaravalloti, N. D., Genova, H. M., & DeLuca, J. (2015) · Frontiers in Neurology · doi:10.3389/fneur.2015.00067 · Cited by 105 · see citing works
Corfield, F., & Langdon, D. W. (2018) · Neurology and Therapy · doi:10.1007/s40120-018-0102-3 · Cited by 94 · see citing works
Progressive multiple sclerosis, cognitive function, and quality of life
Chow, H. H., Schreiber, K. I., Magyari, M., Ammitzbøll, C., Börnsen, L. S., Christensen, J. R., Ratzer, R. L., Sørensen, P. S., & Sellebjerg, F. T. (2018) · Brain and Behavior · doi:10.1002/brb3.875 · Cited by 93 · see citing works
Reorganization in cognitive networks with progression of multiple sclerosis
Loitfelder, M., Fazekas, F., Petrovic, K., Fuchs, S., Ropele, S., Wallner-Blazek, M., Jehna, M., Aspeck, E., Khalil, M., Schmidt, R., et al. (2011) · Neurology · doi:10.1212/wnl.0b013e31820b75cf · Cited by 86 · see citing works
Computerized Cognitive Training in Multiple Sclerosis: A Systematic Review and Meta-analysis
Lampit, A., Heine, J., Finke, C., Barnett, M. H., Valenzuela, M., Wolf, A., Leung, I. H. K., & Hill, N. T. M. (2019) · Neurorehabilitation and neural repair · doi:10.1177/1545968319860490 · Cited by 80 · see citing works
Beyond clinical changes: Rehabilitation-induced neuroplasticity in MS
Prosperini, L., & Filippo, M. D. (2019) · Multiple Sclerosis Journal · doi:10.1177/1352458519846096 · Cited by 75 · see citing works
Polychroniadou, E., Bakirtzis, C., Langdon, D. W., Lagoudaki, R., Kesidou, E., Theotokis, P., Tsalikakis, D., Poulatsidou, K.-N., Kyriazis, O., Boziki, M. K., et al. (2016) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2016.06.011 · Cited by 74 · see citing works
Self-citationPharmacological and Non-pharmacological Therapies of Cognitive Impairment in Multiple Sclerosis
Miller, E. D., Morel, A., Redlicka, J., Miller, I., & Saluk, J. (2018) · Current Neuropharmacology · doi:10.2174/1570159x15666171109132650 · Cited by 69 · see citing works
Papathanasiou, A., Messinis, L., Georgiou, V. L., & Papathanasopoulos, P. (2014) · ISRN Neurology · doi:10.1155/2014/151379 · Cited by 60 · see citing works
Self-citationMessinis, L., Nasios, G., Kosmidis, M. H., et al. (2017) · Behavioural Neurology · doi:10.1155/2017/5919841 · Cited by 59 · see citing works
Self-citationDardiotis, E., Νούσια, Α., Siokas, V., Tsouris, Z., Andravizou, A., Mentis, A. A., Florou, D., Messinis, L., & Nasios, G. (2017) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2017.12.017 · Cited by 56 · see citing works
Self-citationDrugs approved for the treatment of multiple sclerosis: review of their safety profile
Auricchio, F., Scavone, C., Cimmaruta, D., di Mauro, G., Capuano, A., Sportiello, L., & Rafaniello, C. (2017) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2017.1388371 · Cited by 49 · see citing works
Mattioli, F., Stampatori, C., Scarpazza, C., Parrinello, G., & Capra, R. (2012) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2012.06.004 · Cited by 48 · see citing works
Ernst, A., Botzung, A., Gounot, D., Sellal, F., Blanc, F., Seze, J. D., & Manning, L. (2012) · Multiple Sclerosis International · doi:10.1155/2012/820240 · Cited by 44 · see citing works
Bakalidou, D., Voumvourakis, K. I., Tsourti, Z., Papageorgiou, E. G., Πούλιος, Α., & Giannopoulos, S. (2014) · International Journal of Rehabilitation Research · doi:10.1097/mrr.0000000000000057 · Cited by 43 · see citing works
Ntoskou, K., Messinis, L., Nasios, G., Μαρτζούκου, Μ., Makris, G., Panagiotopoulos, E. C., & Papathanasopoulos, P. (2018) · The Open Neurology Journal · doi:10.2174/1874205x01812010019 · Cited by 38 · see citing works
Self-citationAdaptation of the Cognitive Reserve Index Questionnaire (CRIq) for the Greek population
Maiovis, P., Ioannidis, P., Nucci, M., Gotzamani-Psarrakou, A., & Karacostas, D. (2016) · Neurological Sciences · doi:10.1007/s10072-015-2457-x · Cited by 37 · see citing works
Covey, T. J., Shucard, J. L., Benedict, R. H. B., Weinstock‐Guttman, B., & Shucard, D. W. (2018) · Multiple Sclerosis Journal - Experimental Translational and Clinical · doi:10.1177/2055217317747626 · Cited by 37 · see citing works
Charvet, L. E., Shaw, M., Haider, L., Melville, P., & Krupp, L. (2015) · Multiple Sclerosis Journal - Experimental Translational and Clinical · doi:10.1177/2055217315609629 · Cited by 35 · see citing works
Mokhber, N., Azarpazhooh, A., Orouji, E., et al. (2014) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2014.01.038 · Cited by 32 · see citing works
Impact of Pharmacotherapy on Cognitive Dysfunction in Patients with Multiple Sclerosis
Roy, S., Benedict, R. H. B., Drake, A. S., & Weinstock‐Guttman, B. (2016) · CNS Drugs · doi:10.1007/s40263-016-0319-6 · Cited by 28 · see citing works
Quality of life in multiple sclerosis: Effects of current treatment options
Kargiotis, O., Paschali, A. N., Messinis, L., & Papathanasopoulos, P. (2010) · International Review of Psychiatry · doi:10.3109/09540261003589521 · Cited by 27 · see citing works
Self-citationCognitive 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
Self-citationFitness to drive in multiple sclerosis: Awareness of deficit moderates risk
Ryan, K. A., Rapport, L. J., Harper, K. T., Fuerst, D. R., Bieliauskas, L. A., Khan, O., & Lisak, R. P. (2008) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803390802119922 · Cited by 26 · see citing works
D’Amico, E., Leone, C., Tumani, H., & Patti, F. (2016) · Multiple Sclerosis Journal · doi:10.1177/1352458516632066 · Cited by 21 · see citing works
Neuropsychological Features of Multiple Sclerosis: Impact and Rehabilitation
Messinis, L., Papathanasopoulos, P., Kosmidis, M. H., et al. (2018) · Behavioural Neurology · doi:10.1155/2018/4831647 · Cited by 14 · see citing works
Self-citationBenedict, R. H. B., Cree, B., Tomic, D., et al. (2018) · Neurology · doi:10.1212/wnl.90.15_supplement.s44.004 · Cited by 12 · see citing works
Treatment of cognitive impairment in secondary progressive MS
Feinstein, A. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.109 · Cited by 3 · see citing works
EXPLORING COGNITION IN SECONDARY PROGRESSIVE MULTIPLE SCLEROSIS (SPMS)
Doshi, A., Plantone, D., DeAngelis, F., et al. (2016) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2016-315106.129 · Cited by 1 · see citing works
Neuropsychological Functions and Cognitive Neurorehabilitation in Multiple Sclerosis
Messinis, L., Nasios, G., & Papathanasopouos, P. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.85511 · Cited by 1 · see citing works
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Liu, M., Qian, Q., Wang, W., Chen, L., Wang, L., Zhou, Y., Xu, S., Wu, J., Feng, T., Zhu, Z., et al. (2022) · PM&R · doi:10.1002/pmrj.12679 · Cited by 18 · see citing works
Bogosian, A., Day, F., Norton, S., Silber, E., Sakel, M., Sharrack, B., & Moss-Morris, R. (2022) · Frontiers in Rehabilitation Sciences · doi:10.3389/fresc.2022.966133 · Cited by 5 · see citing works
“There is some preliminary evidence showing the need expressed by people with SPMS for psychological support and a personalised care plan (60), as well as some preliminary evidence of the effectiveness of a computer-based cognitive neurorehabilitation (61).”
Background
- Authors
- Messinis, L., Kosmidis, M. H., Nasios, G., Konitsiotis, S., Ntoskou, A., Bakirtzis, C., Grigoriadis, N., Patrikelis, P., Panagiotopoulos, E., Gourzis, P., Malefaki, S., & Papathanasopoulos, P.
- Affiliations
- University of Patras (GR)
- Aristotle University of Thessaloniki (GR)
- University of Ioannina (GR)
- AHEPA University Hospital (GR)
- National and Kapodistrian University of Athens (GR)
- Corresponding author
- Messinis, Lambros
- ORCID
- Venue
- Multiple Sclerosis and Related Disorders
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 39
- Pages
- 101932
- ISSN
- 2211-0348 (ISSN-L)
- OpenAlex
- W2999572799
- Cited by
- 40
- References
- 59
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 7 · 2023: 6 · 2022: 7 · 2021: 6 · 2020: 5
- FWCI
- 3.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Multiple Sclerosis and Related Disorders (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Functions and Memory
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- secondary progressive multiple sclerosis, cognitive impairment, computer-based cognitive rehabilitation, home-based intervention, verbal learning, visuospatial memory, processing speed, fatigue, depression, quality of life, BICAMS, cognitive reserve, medication adherence, relapse rate, disease-modifying therapy
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