Cognitive function in multiple sclerosis improves with telerehabilitation: Results from a randomized controlled trial

Leigh E Charvet, Jie Yang, Michael T Shaw, Kathleen Sherman, Lamia Haider, Jianjin Xu, Lauren B Krupp, Leigh E Charvet, Jie Yang, Michael T Shaw, Kathleen Sherman, Lamia Haider, Jianjin Xu, Lauren B Krupp

Abstract

Cognitive impairment affects more than half of all individuals living with multiple sclerosis (MS). We hypothesized that training at home with an adaptive online cognitive training program would have greater cognitive benefit than ordinary computer games in cognitively-impaired adults with MS. This was a double-blind, randomized, active-placebo-controlled trial. Participants with MS were recruited through Stony Brook Medicine and randomly assigned to either the adaptive cognitive remediation (ACR) program or active control of ordinary computer games for 60 hours over 12 weeks. Training was remotely-supervised and delivered through a study-provided laptop computer. A computer generated, blocked stratification table prepared by statistician provided the randomization schedule and condition was assigned by a study technician. The primary outcome, administered by study psychometrician, was measured by change in a neuropsychological composite measure from baseline to study end. An intent-to-treat analysis was employed and missing primary outcome values were imputed via Markov Chain Monte Carlo method. Participants in the ACR (n = 74) vs. active control (n = 61) training program had significantly greater improvement in the primary outcome of cognitive functioning (mean change in composite z score±SD: 0·25±0·45 vs. 0·09±0·37, p = 0·03, estimated difference = 0·16 with 95% CI: 0·02-0·30), despite greater training time in the active control condition (mean±SD:56·9 ± 34·6 vs. 37·7 ±23 ·8 hours played, p = 0·006). This study provides Class I evidence that adaptive, computer-based cognitive remediation accessed from home can improve cognitive functioning in MS. This telerehabilitation approach allowed for rapid recruitment and high compliance, and can be readily applied to other neurological conditions associated with cognitive dysfunction.

Trial registration: Clinicaltrials.gov NCT02141386.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Consort flow diagram.
Fig 1. Consort flow diagram.
Fig 2. Change in z score across…
Fig 2. Change in z score across measures by condition.
*Indicates a significant difference corresponding to a p value

Fig 3. Total time spent in program…

Fig 3. Total time spent in program by condition.

*Greater time was spent in program…

Fig 3. Total time spent in program by condition.
*Greater time was spent in program by the active control condition (p = 0.006).
Fig 3. Total time spent in program…
Fig 3. Total time spent in program by condition.
*Greater time was spent in program by the active control condition (p = 0.006).

References

    1. Benedict RH, Zivadinov R. Risk factors for and management of cognitive dysfunction in multiple sclerosis. Nature reviews Neurology. 2011;7(6):332–42. 10.1038/nrneurol.2011.61
    1. Rocca MA, Amato MP, De Stefano N, Enzinger C, Geurts JJ, Penner IK,.et al. Clinical and imaging assessment of cognitive dysfunction in multiple sclerosis. The Lancet Neurology. 2015; Published online 2.5.15.
    1. Stuifbergen AK, Becker H, Perez F, Morison J, Kullberg V, Todd A. A randomized controlled trial of a cognitive rehabilitation intervention for persons with multiple sclerosis. Clinical rehabilitation. 2012;26(10):882–93. 10.1177/0269215511434997
    1. O'Brien AR, Chiaravalloti N, Goverover Y, Deluca J. Evidenced-based cognitive rehabilitation for persons with multiple sclerosis: a review of the literature. Archives of physical medicine and rehabilitation. 2008;89(4):761–9. 10.1016/j.apmr.2007.10.019
    1. Rosti-Otajarvi EM, Hamalainen PI. Neuropsychological rehabilitation for multiple sclerosis. The Cochrane database of systematic reviews. 2011;(11):CD009131.
    1. Chiaravalloti ND, Moore NB, Nikelshpur OM, DeLuca J. An RCT to treat learning impairment in multiple sclerosis: The MEMREHAB trial. Neurology. 2013;81(24):2066–72. 10.1212/01.wnl.0000437295.97946.a8
    1. Lampit A, Hallock H, Valenzuela M. Computerized cognitive training in cognitively healthy older adults: a systematic review and meta-analysis of effect modifiers. PLoS medicine. 2014;11(11):e1001756 10.1371/journal.pmed.1001756
    1. Mishra J, de Villers-Sidani E, Merzenich M, Gazzaley A. Adaptive training diminishes distractibility in aging across species. Neuron. 2014;84(5):1091–103. 10.1016/j.neuron.2014.10.034
    1. Merzenich MM, Van Vleet TM, Nahum M. Brain plasticity-based therapeutics. Frontiers in human neuroscience. 2014;8:385 10.3389/fnhum.2014.00385
    1. Vinogradov S, Fisher M, de Villers-Sidani E. Cognitive training for impaired neural systems in neuropsychiatric illness. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology. 2012;37(1):43–76.
    1. Charvet L, Shaw M, Haider L, Melville P, Krupp L. Remotely-delivered cognitive remediation in multiple sclerosis (MS): protocol and results from a pilot study. Multiple Sclerosis Journal—Experimental, Translational and Clinical. 2015;1.
    1. Mahncke HW, Connor BB, Appelman J, Ahsanuddin ON, Hardy JL, Wood RA, et al. Memory enhancement in healthy older adults using a brain plasticity-based training program: a randomized, controlled study. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(33):12523–8. 10.1073/pnas.0605194103
    1. Keefe RS, Vinogradov S, Medalia A, Buckley PF, Caroff SN, D'Souza DC, et al. Feasibility and pilot efficacy results from the multisite Cognitive Remediation in the Schizophrenia Trials Network (CRSTN) randomized controlled trial. The Journal of clinical psychiatry. 2012;73(7):1016–22. 10.4088/JCP.11m07100
    1. Hancock LM, Bruce JM, Bruce AS, Lynch SG. Processing speed and working memory training in multiple sclerosis: a double-blind randomized controlled pilot study. Journal of clinical and experimental neuropsychology. 2015;37(2):113–27. 10.1080/13803395.2014.989818
    1. Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Annals of neurology. 2011;69(2):292–302. 10.1002/ana.22366
    1. Smith A. The Symbol Digit Modalities Test (SDMT) Symbol Digit Modalities Test: Manual.: Western Psychological Services; 1982.
    1. Parmenter BA, Weinstock-Guttman B, Garg N, Munschauer F, Benedict RH. Screening for cognitive impairment in multiple sclerosis using the Symbol digit Modalities Test. Multiple sclerosis. 2007;13(1):52–7. 10.1177/1352458506070750
    1. BrainHQ. Posit Science; 2015.
    1. Gaming H. Hoyle Puzzles and Board Games. 2008 ed: WD Encore Software, LLC.
    1. Fisher M, Holland C, Merzenich MM, Vinogradov S. Using neuroplasticity-based auditory training to improve verbal memory in schizophrenia. The American journal of psychiatry. 2009;166(7):805–11. 10.1176/appi.ajp.2009.08050757
    1. Fisher M, Loewy R, Carter C, Lee A, Ragland JD, Niendam T, et al. Neuroplasticity-based auditory training via laptop computer improves cognition in young individuals with recent onset schizophrenia. Schizophrenia bulletin. 2015;41(1):250–8. 10.1093/schbul/sbt232
    1. Loewy R, Fisher M, Schlosser DA, Biagianti B, Stuart B, Mathalon DH, et al. Intensive Auditory Cognitive Training Improves Verbal Memory in Adolescents and Young Adults at Clinical High Risk for Psychosis. Schizophrenia bulletin. 2016;42 Suppl 1:S118–26.
    1. Tombaugh TN. A comprehensive review of the Paced Auditory Serial Addition Test (PASAT). Archives of clinical neuropsychology: the official journal of the National Academy of Neuropsychologists. 2006;21(1):53–76.
    1. Hartman DE. Wechsler Adult Intelligence Scale IV (WAIS IV): return of the gold standard. Applied neuropsychology. 2009;16(1):85–7. 10.1080/09084280802644466
    1. Scherl WF, Krupp LB, Christodoulou C, Morgan TM, Hyman L, Chandler B, et al. Normative data for the selective reminding test: a random digit dialing sample. Psychological reports. 2004;95(2):593–603. 10.2466/pr0.95.2.593-603
    1. Benedict RH. Brief Visuospatial Memory Test—Revised: Professional Manual. Odessa, FL: Psychological Assessment Resources, Inc; 2007.
    1. Delis DC, Kaplan E, Kramer JH. Delis-Kaplan Executive Function System (D-KEFS) Examiner's Manual. San Antonio, TX: The Psychological Corporation; 2001. 1–218 p.
    1. Parmenter BA, Zivadinov R, Kerenyi L, Gavett R, Weinstock-Guttman B, Dwyer MG, et al. Validity of the Wisconsin Card Sorting and Delis-Kaplan Executive Function System (DKEFS) Sorting Tests in multiple sclerosis. Journal of clinical and experimental neuropsychology. 2007;29(2):215–23. 10.1080/13803390600672163
    1. University V. REDCap—Research Electronic Database Capture. 6.10.0 ed: Vanderbilt University; 2016.
    1. Rubin DB. Multiple Imputation for Nonresponse in Surveys. New York: John Wiley & Sons, Inc; 1987.
    1. Little RJ, Rubin DB. Statistical Analysis with Missing Data. New York: John Wiley & Sons, Inc; 1987.
    1. McCabe JA, Redick TS, Engle RW. Brain-Training Pessimism, but Applied-Memory Optimism. Psychological science in the public interest: a journal of the American Psychological Society. 2016;17(3):187–91.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere