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Neurological update: cognitive rehabilitation in multiple sclerosis


Cognitive impairment is a common and debilitating symptom in multiple sclerosis (MS). There is limited evidence that disease-modifying therapies are effective in treating cognitive dysfunction. Cognitive rehabilitation is a promising approach to treat cognitive dysfunction in MS, gaining empirical support over the last 10 years. The current review will provide a brief overview of cognitive rehabilitation in MS. Overall, there is evidence that cognitive rehabilitation programs (either restorative or compensatory) are efficacious in treating MS-related cognitive dysfunction. Clinicians should consider this low-cost, low-risk, yet effective treatment approach for their patients.

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  1. 1.

    Wallin MT, Culpepper WJ, Nichols E, Bhutta ZA, Gebrehiwot TT, Hay SI, Khalil IA, Krohn KJ, Liang X, Naghavi M (2019) Global, regional, and national burden of multiple sclerosis 1990–2016: a systematic analysis for the global burden of disease study 2016. The Lancet Neurology 18(3):269–285

    Article  Google Scholar 

  2. 2.

    Koch-Henriksen N, Sørensen PS (2010) The changing demographic pattern of multiple sclerosis epidemiology. The Lancet Neurology 9(5):520–532

    PubMed  Article  Google Scholar 

  3. 3.

    Ruano L, Portaccio E, Goretti B, Niccolai C, Severo M, Patti F, Cilia S, Gallo P, Grossi P, Ghezzi A (2017) Age and disability drive cognitive impairment in multiple sclerosis across disease subtypes. Mult Scler J 23(9):1258–1267

    Article  Google Scholar 

  4. 4.

    Langdon D (2011) Cognition in multiple sclerosis. Curr Opin Neurol 24(3):244–249

    PubMed  Article  Google Scholar 

  5. 5.

    Goverover Y, Chiaravalloti ND, DeLuca J (2019) Money management in multiple sclerosis: the role of cognitive, motor and affective factors. Front Neurol 10:1128

    Article  Google Scholar 

  6. 6.

    Strober LB, Christodoulou C, Benedict RH, Westervelt HJ, Melville P, Scherl WF, Weinstock-Guttman B, Rizvi S, Goodman AD, Krupp LB (2012) Unemployment in multiple sclerosis: the contribution of personality and disease. Mult Scler J 18(5):647–653

    Article  Google Scholar 

  7. 7.

    Chen MH, Goverover Y, Genova HM, DeLuca J (2020) Cognitive efficacy of pharmacologic treatments in multiple sclerosis: a systematic review. CNS Drugs.

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Rosti-Otajärvi E, Ruutiainen J, Huhtala H, Hämäläinen P (2014) Cognitive performance profile in different phenotypes of MS with cognitive complaints. Mult Scler Relat Disord 3(4):463–472

    PubMed  Article  Google Scholar 

  9. 9.

    Chiaravalloti ND, DeLuca J (2008) Cognitive impairment in multiple sclerosis. The Lancet Neurology 7(12):1139–1151

    PubMed  Article  Google Scholar 

  10. 10.

    Damasceno A, Pimentel-Silva LR, Damasceno BP, Cendes F (2019) Cognitive trajectories in relapsing–remitting multiple sclerosis: a longitudinal 6 year study. Mult Scler J 26(13):1740-1751

    Article  Google Scholar 

  11. 11.

    Pitteri M, Romualdi C, Magliozzi R, Monaco S, Calabrese M (2017) Cognitive impairment predicts disability progression and cortical thinning in MS: an 8 year study. Mult Scler J 23(6):848–854

    Article  Google Scholar 

  12. 12.

    Kalb R, Beier M, Benedict RH, Charvet L, Costello K, Feinstein A, Gingold J, Goverover Y, Halper J, Harris C (2018) Recommendations for cognitive screening and management in multiple sclerosis care. Mult Scler J 24(13):1665–1680

    Article  Google Scholar 

  13. 13.

    DeLuca J, Chiaravalloti ND, Sandroff BM (2020) Treatment and management of cognitive dysfunction in patients with multiple sclerosis. Nat Rev Neurol 16:1–14

    Article  Google Scholar 

  14. 14.

    Cicerone KD, Goldin Y, Ganci K, Rosenbaum A, Wethe JV, Langenbahn DM, Malec JF, Bergquist TF, Kingsley K, Nagele D (2019) Evidence-Based cognitive rehabilitation: systematic review of the literature from 2009 through 2014. Arch Phys Med Rehabil 100(8):1515–1533

    PubMed  Article  Google Scholar 

  15. 15.

    Amato M, Goretti B, Viterbo R, Portaccio E, Niccolai C, Hakiki B, Iaffaldano P, Trojano M (2014) Computer-assisted rehabilitation of attention in patients with multiple sclerosis: results of a randomized, double-blind trial. Mult Scler J 20(1):91–98

    CAS  Article  Google Scholar 

  16. 16.

    Cerasa A, Gioia MC, Valentino P, Nisticò R, Chiriaco C, Pirritano D, Tomaiuolo F, Mangone G, Trotta M, Talarico T (2013) Computer-assisted cognitive rehabilitation of attention deficits for multiple sclerosis: a randomized trial with fMRI correlates. Neurorehabil Neural Repair 27(4):284–295

    PubMed  Article  Google Scholar 

  17. 17.

    Mattioli F, Stampatori C, Bellomi F, Danni M, Compagnucci L, Uccelli A, Pardini M, Santuccio G, Fregonese G, Pattini M (2015) A RCT comparing specific intensive cognitive training to aspecific psychological intervention in RRMS: the SMICT study. Front Neurol 5:278

    PubMed  PubMed Central  Article  Google Scholar 

  18. 18.

    Campbell J, Langdon D, Cercignani M, Rashid W (2016) A randomised controlled trial of efficacy of cognitive rehabilitation in multiple sclerosis: a cognitive, behavioural, and MRI study. Neural Plast 2016:4292585

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. 19.

    Charvet LE, Yang J, Shaw MT, Sherman K, Haider L, Xu J, Krupp LB (2017) Cognitive function in multiple sclerosis improves with telerehabilitation: results from a randomized controlled trial. PLoS ONE 12(5):e0177177

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  20. 20.

    Chiaravalloti ND, Moore NB, Nikelshpur OM, DeLuca J (2013) An RCT to treat learning impairment in multiple sclerosis: the MEMREHAB trial. Neurology 81(24):2066–2072

    PubMed  PubMed Central  Article  Google Scholar 

  21. 21.

    Goverover Y, Chiaravalloti N, Genova H, DeLuca J (2018) A randomized controlled trial to treat impaired learning and memory in multiple sclerosis: the self-GEN trial. Mult Scler J 24(8):1096–1104

    Article  Google Scholar 

  22. 22.

    Slamecka NJ, Graf P (1978) The generation effect: Delineation of a phenomenon. J Exp Psychol: Human Learn Memory 4(6):592

    Google Scholar 

  23. 23.

    Bjork RA (1988) Retrieval practice and the maintenance of knowledge. In M. M. Gruneberg, P. E. Morris, & R. N. Sykes (Eds.), Practical aspects of memory II (pp. 396–401). London: Wiley

  24. 24.

    Krug D, Davis TB, Glover JA (1990) Massed versus distributed repeated reading: a case of forgetting helping recall? J Educ Psychol 82(2):366

    Article  Google Scholar 

  25. 25.

    Chiaravalloti ND, Moore NB, Weber E, DeLuca J (2019) The application of strategy-based training to enhance memory (STEM) in multiple sclerosis: a pilot RCT. Neuropsychol Rehabil 31(2):231–254

    PubMed  Article  Google Scholar 

  26. 26.

    Mani A, Chohedri E, Ravanfar P, Mowla A, Nikseresht A (2018) Efficacy of group cognitive rehabilitation therapy in multiple sclerosis. Acta Neurol Scand 137(6):589–597

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Klein OA, Drummond A, Mhizha-Murira JR, Mansford L, das Nair R (2019) Effectiveness of cognitive rehabilitation for people with multiple sclerosis: a meta-synthesis of patient perspectives. Neuropsychol Rehabil 29(4):491–512

    PubMed  Article  Google Scholar 

  28. 28.

    das Nair R, Martin KJ, Lincoln NB (2016) Memory rehabilitation for people with multiple sclerosis. Cochrane Database Syst Rev 3:CD008754

    PubMed  Google Scholar 

  29. 29.

    Rosti-Otajärvi EM, Hämäläinen PI (2014) Neuropsychological rehabilitation for multiple sclerosis. Cochrane Database Syst Rev 2:Cd009131.

    Article  Google Scholar 

  30. 30.

    Guyatt GH, Thorlund K, Oxman AD, Walter SD, Patrick D, Furukawa TA, Johnston BC, Karanicolas P, Akl EA, Vist G (2013) GRADE guidelines: 13. Preparing summary of findings tables and evidence profiles—continuous outcomes. J Clin Epidemiol 66(2):173–183

    PubMed  Article  Google Scholar 

  31. 31.

    Guyatt GH, Oxman AD, Santesso N, Helfand M, Vist G, Kunz R, Brozek J, Norris S, Meerpohl J, Djulbegovic B (2013) GRADE guidelines: 12. Preparing summary of findings tables—binary outcomes. J Clin Epidemiol 66(2):158–172

    PubMed  Article  Google Scholar 

  32. 32.

    Taylor L, Mhizha-Murira J, Smith L, Potter K-J, Wong D, Evangelou N, Lincoln N, das Nair R (2021) Memory rehabilitation for people with multiple sclerosis. Cochrane Database of Systematic Reviews, In Press

  33. 33.

    Goverover Y, Chiaravalloti ND, O’Brien AR, DeLuca J (2018) Evidenced-based cognitive rehabilitation for persons with multiple sclerosis: an updated review of the literature from 2007 to 2016. Arch Phys Med Rehabil 99(2):390–407

    PubMed  Article  Google Scholar 

  34. 34.

    Gronseth GS, Cox J, Gloss D, Merillat S, Dittman J, Armstrong MJ, Getchius TSD (2017) 2017 Edition clinical practice guideline process manual. American Academy of Neurology

    Google Scholar 

  35. 35.

    Cicerone KD, Langenbahn DM, Braden C, Malec JF, Kalmar K, Fraas M, Felicetti T, Laatsch L, Harley JP, Bergquist T (2011) Evidence-based cognitive rehabilitation: updated review of the literature from 2003 through 2008. Arch Phys Med Rehabil 92(4):519–530

    PubMed  Article  Google Scholar 

  36. 36.

    Dardiotis E, Nousia A, Siokas V, Tsouris Z, Andravizou A, Mentis A-FA, Florou D, Messinis L, Nasios G (2018) Efficacy of computer-based cognitive training in neuropsychological performance of patients with multiple sclerosis: a systematic review and meta-analysis. Mult Scler Relat Disord 20:58–66

    PubMed  Article  Google Scholar 

  37. 37.

    Lampit A, Heine J, Finke C, Barnett MH, Valenzuela M, Wolf A, Leung IH, Hill NT (2019) Computerized cognitive training in multiple sclerosis: a systematic review and meta-analysis. Neurorehabil Neural Repair 33(9):695–706

    PubMed  Article  Google Scholar 

  38. 38.

    Goodwin R, Lincoln N, das Nair R, Bateman A (2017) External memory aids for memory problems in people with multiple sclerosis: a systematic review. Neuropsychol Rehabil 27(8):1081–1102

    PubMed  Article  Google Scholar 

  39. 39.

    Mitolo M, Venneri A, Wilkinson ID, Sharrack B (2015) Cognitive rehabilitation in multiple sclerosis: a systematic review. J Neurol Sci 354(1–2):1–9

    PubMed  Article  Google Scholar 

  40. 40.

    U.S. Preventive Services Task Force (1989) Guide to clinical preventive services: report of the U.S. Preventive Services Task Force.

  41. 41.

    Dacosta-Aguayo R, Genova H, Chiaravalloti ND, DeLuca J (2020) Neuroimaging and rehabilitation in multiple sclerosis. Cognitive rehabilitation and neuroimaging. Springer, pp 117–138

    Chapter  Google Scholar 

  42. 42.

    Prosperini L, Piattella MC, Giannì C, Pantano P (2015) Functional and structural brain plasticity enhanced by motor and cognitive rehabilitation in multiple sclerosis. Neural Plast 2015:481574

    PubMed  PubMed Central  Article  Google Scholar 

  43. 43.

    Penner I-K, Kappos L, Opwis K (2005) Induced changes in brain activation using a computerized attention training in patients with multiple sclerosis (2005). In Opwis, K. and Penner, I. -K. (eds) Proceedings of KogWis05 : the German Cognitive Science Conference 2005 : September 7th-9th, 2005, Basel, Switzerland, Department of Psychology, University of Basel. Basel

  44. 44.

    Huiskamp M, Dobryakova E, Wylie G, DeLuca J, Chiaravalloti N (2016) A pilot study of changes in functional brain activity during a working memory task after mSMT treatment: the MEMREHAB trial. Mult Scler Relat Disord 7:76–82

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  45. 45.

    Leavitt VM, Wylie GR, Girgis PA, DeLuca J, Chiaravalloti ND (2014) Increased functional connectivity within memory networks following memory rehabilitation in multiple sclerosis. Brain Imaging Behav 8(3):394–402

    PubMed  Article  Google Scholar 

  46. 46.

    Bonavita S, Gallo A, Sacco R, Corte MD, Bisecco A, Docimo R, Lavorgna L, Corbo D, Costanzo AD, Tortora F (2011) Distributed changes in default-mode resting-state connectivity in multiple sclerosis. Mult Scler J 17(4):411–422

    Article  Google Scholar 

  47. 47.

    Parisi L, Rocca MA, Mattioli F, Copetti M, Capra R, Valsasina P, Stampatori C, Filippi M (2014) Changes of brain resting state functional connectivity predict the persistence of cognitive rehabilitation effects in patients with multiple sclerosis. Mult Scler J 20(6):686–694

    Article  Google Scholar 

  48. 48.

    Spreng RN, Grady CL (2010) Patterns of brain activity supporting autobiographical memory, prospection, and theory of mind, and their relationship to the default mode network. J Cogn Neurosci 22(6):1112–1123

    PubMed  Article  Google Scholar 

  49. 49.

    Feinstein A (2006) Mood disorders in multiple sclerosis and the effects on cognition. J Neurol Sci 245(1–2):63–66

    PubMed  Article  Google Scholar 

  50. 50.

    Braley TJ, Kratz AL, Kaplish N, Chervin RD (2016) Sleep and cognitive function in multiple sclerosis. Sleep 39(8):1525–1533

    PubMed  PubMed Central  Article  Google Scholar 

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The preparation of this manuscript was supported in part by the National Multiple Sclerosis Society (NMSS) Grant MB-1606-08779 to John DeLuca, and funding by Kessler Foundation.

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Correspondence to John DeLuca.

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Conflicts of interest

Dr. John DeLuca received consulting fees/honorarium from Biogen, Sanofi—Genzyme, Novartis, Roche and Celgene. He has received grant funding from Biogen, EMD Serono, National Multiple Sclerosis Society (NMSS), Consortium of Multiple Sclerosis Centers (CMSC), and the National Institute of Health (NIH). Dr. Nancy Chiaravalloti received consulting fees/honorarium from Roche and Akili Interactive Labs. She has received grant funding from the NMSS, CMSC, and the NIH. Dr. Michelle Chen has received grant funding from the National Academy of Neuropsychology and the New Jersey Health Foundation.

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Chen, M.H., Chiaravalloti, N.D. & DeLuca, J. Neurological update: cognitive rehabilitation in multiple sclerosis. J Neurol (2021).

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  • Multiple sclerosis
  • Cognitive rehabilitation
  • Cognitive remediation
  • Cognitive impairment