Top

Published in:

Open Access 01-12-2024 | Multiple Sclerosis | Study Protocol

Don’t be late! Postponing cognitive decline and preventing early unemployment in people with multiple sclerosis: a study protocol

Authors: Jip Aarts, Shalina R. D. Saddal, Judith E. Bosmans, Vincent de Groot, Brigit A. de Jong, Martin Klein, Marit F. L. Ruitenberg, Frederieke G. Schaafsma, Esther C. F. Schippers, Menno M. Schoonheim, Bernard M. J. Uitdehaag, Sabina van der Veen, Pauline T. Waskowiak, Guy A. M. Widdershoven, Karin van der Hiele, Hanneke E. Hulst, on behalf of the Don’t be late! consortium

Published in: BMC Neurology | Issue 1/2024

Abstract

Background

Up to 65% of people with multiple sclerosis (PwMS) develop cognitive deficits, which hampers their ability to work, participating in day-to-day life and ultimately reducing quality of life (QoL). Early cognitive symptoms are often less tangible to PwMS and their direct environment and are noticed only when symptoms and work functioning problems become more advanced, i.e., when (brain) damage is already advanced. Treatment of symptoms at a late stage can lead to cognitive impairment and unemployment, highlighting the need for preventative interventions in PwMS.

Aims

This study aims to evaluate the (cost-) effectiveness of two innovative preventative interventions, aimed at postponing cognitive decline and work functioning problems, compared to enhanced usual care in improving health-related QoL (HRQoL).

Methods

Randomised controlled trial including 270 PwMS with mild cognitive impairment, who have paid employment ≥ 12 h per week and are able to participate in physical exercise (Expanded Disability Status Scale < 6.0). Participants are randomised across three study arms: 1) ‘strengthening the brain’ – a lifestyle intervention combining personal fitness, mental coaching, dietary advice, and cognitive training; 2) ‘strengthening the mind’ – a work-focused intervention combining the capability approach and the participatory approach in one-on-one coaching by trained work coaches who have MS themselves; 3) Control group—receiving general information about cognitive impairment in MS and receiving care as usual. Intervention duration is four months, with short-term and long-term follow-up measurements at 10 and 16 months, respectively. The primary outcome measure of the Don’t be late! intervention study will be HRQoL as measured with the 36-item Short Form. Secondary outcomes include cognition, work related outcomes, physical functioning, structural and functional brain changes, psychological functioning, and societal costs. Semi-structured interviews and focus groups with stakeholders will be organised to qualitatively reflect on the process and outcome of the interventions.

Discussion

This study seeks to prevent (further) cognitive decline and job loss due to MS by introducing tailor-made interventions at an early stage of cognitive symptoms, thereby maintaining or improving HRQoL. Qualitative analyses will be performed to allow successful implementation into clinical practice.

Trial registration

Retrospectively registered at ClinicalTrials.gov with reference number NCT06068582 on 10 October 2023.

Thompson AJ, Baranzini SE, Geurts J, Hemmer B, Ciccarelli O. Multiple sclerosis. Lancet. 2018;391(10130):1622–36. https://doi.org/10.1016/S0140-6736(18)30481-1.CrossRefPubMed

Uitdehaag B, Kobelt G, Berg J, Capsa D, Dalen J, European Multiple Sclerosis P. New insights into the burden and costs of multiple sclerosis in Europe: Results for the Netherlands. Mult Scler. 2017;23(2_suppl):117–29. https://doi.org/10.1177/1352458517708663.CrossRefPubMed

Walton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA, et al. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Multiple Scler J. 2020;26(14):1816–21. https://doi.org/10.1177/1352458520970841.CrossRef

Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372(9648):1502–17. https://doi.org/10.1016/S0140-6736(08)61620-7.CrossRefPubMed

Eijlers AJC, van Geest Q, Dekker I, Steenwijk MD, Meijer KA, Hulst HE, et al. Predicting cognitive decline in multiple sclerosis: a 5-year follow-up study. Brain. 2018;141(9):2605–18. https://doi.org/10.1093/brain/awy202.CrossRefPubMed

Sumowski JF, Benedict R, Enzinger C, Filippi M, Geurts JJ, Hamalainen P, et al. Cognition in multiple sclerosis: State of the field and priorities for the future. Neurology. 2018;90(6):278–88. https://doi.org/10.1212/WNL.0000000000004977.CrossRefPubMedPubMedCentral

Campbell J, Rashid W, Cercignani M, Langdon D. Cognitive impairment among patients with multiple sclerosis: associations with employment and quality of life. Postgrad Med J. 2017;93(1097):143–7. https://doi.org/10.1136/postgradmedj-2016-134071.CrossRefPubMed

Kornblith AB, La Rocca NG, Baum HM. Employment in individuals with multiple sclerosis. Int J Rehabil Res. 1986;9(2):155–65. https://doi.org/10.1097/00004356-198606000-00006.CrossRefPubMed

van der Hiele K, van Gorp D, Ruimschotel R, Kamminga N, Visser L, Middelkoop H. Work Participation and Executive Abilities in Patients with Relapsing-Remitting Multiple Sclerosis. PLoS One. 2015;10(6):e0129228. https://doi.org/10.1371/journal.pone.0129228.CrossRefPubMedPubMedCentral

10.

van Gorp DAM, van der Hiele K, Heerings MAP, Jongen PJ, van der Klink JJL, Reneman MF, et al. Cognitive functioning as a predictor of employment status in relapsing-remitting multiple sclerosis: a 2-year longitudinal study. Neurol Sci. 2019;40(12):2555–64. https://doi.org/10.1007/s10072-019-03999-w.CrossRefPubMedPubMedCentral

11.

Benedict RH, Rodgers JD, Emmert N, Kininger R, Weinstock-Guttman B. Negative work events and accommodations in employed multiple sclerosis patients. Mult Scler. 2014;20(1):116–9. https://doi.org/10.1177/1352458513494492.CrossRefPubMed

12.

Kordovski VM, Frndak SE, Fisher CS, Rodgers J, Weinstock-Guttman B, Benedict RH. Identifying employed multiple sclerosis patients at-risk for job loss: When do negative work events pose a threat? Mult Scler Relat Disord. 2015;4(5):409–13. https://doi.org/10.1016/j.msard.2015.07.005.CrossRefPubMed

13.

Benedict RHB, Amato MP, DeLuca J, Geurts JJG. Cognitive impairment in multiple sclerosis: clinical management, MRI, and therapeutic avenues. Lancet Neurol. 2020;19(10):860–71. https://doi.org/10.1016/S1474-4422(20)30277-5.CrossRefPubMedPubMedCentral

14.

Goverover Y, Chiaravalloti ND, O’Brien AR, DeLuca J. Evidenced-based cognitive rehabilitation for persons with multiple sclerosis: an updated review of the literature from 2007 to 2016. Arch Phys Med Rehabil. 2018;99(2):390–407. https://doi.org/10.1016/j.apmr.2017.07.021.CrossRefPubMed

15.

Fuchs TA, Ziccardi S, Dwyer MG, Charvet LE, Bartnik A, Campbell R, et al. Response heterogeneity to home-based restorative cognitive rehabilitation in multiple sclerosis: An exploratory study. Mult Scler Relat Disord. 2019;34:103–11. https://doi.org/10.1016/j.msard.2019.06.026.CrossRefPubMed

16.

Prouskas SE, Schoonheim MM, Huiskamp M, Steenwijk MD, Gehring K, Barkhof F, et al. A randomized trial predicting response to cognitive rehabilitation in multiple sclerosis: Is there a window of opportunity? Mult Scler. 2022:13524585221103134. https://doi.org/10.1177/13524585221103134.

17.

Huiskamp M, Moumdjian L, van Asch P, Popescu V, Schoonheim MM, Steenwijk MD, et al. A pilot study of the effects of running training on visuospatial memory in MS: A stronger functional embedding of the hippocampus in the default-mode network? Mult Scler. 2020;26(12):1594–8. https://doi.org/10.1177/1352458519863644.CrossRefPubMed

18.

Motl RW, Sandroff BM, DeLuca J. Exercise training and cognitive rehabilitation: a symbiotic approach for rehabilitating walking and cognitive functions in multiple sclerosis? Neurorehabil Neural Repair. 2016;30(6):499–511. https://doi.org/10.1177/1545968315606993.CrossRefPubMed

19.

Dalgas U. Exercise therapy in multiple sclerosis and its effects on function and the brain. Neurodegener Dis Manag. 2017;7(6s):35–40. https://doi.org/10.2217/nmt-2017-0040.CrossRefPubMed

20.

Filippi M, Riccitelli G, Mattioli F, Capra R, Stampatori C, Pagani E, et al. Multiple sclerosis: effects of cognitive rehabilitation on structural and functional MR imaging measures–an explorative study. Radiology. 2012;262(3):932–40. https://doi.org/10.1148/radiol.11111299.CrossRefPubMed

21.

Parisi L, Rocca MA, Mattioli F, Copetti M, Capra R, Valsasina P, et al. Changes of brain resting state functional connectivity predict the persistence of cognitive rehabilitation effects in patients with multiple sclerosis. Mult Scler. 2014;20(6):686–94. https://doi.org/10.1177/1352458513505692.CrossRefPubMed

22.

Sastre-Garriga J, Alonso J, Renom M, Arévalo MJ, González I, Galán I, et al. A functional magnetic resonance proof of concept pilot trial of cognitive rehabilitation in multiple sclerosis. Mult Scler. 2011;17(4):457–67. https://doi.org/10.1177/1352458510389219.CrossRefPubMed

23.

Karssemeijer EGA, Aaronson JA, Bossers WJ, Smits T, Olde Rikkert MGM, Kessels RPC. Positive effects of combined cognitive and physical exercise training on cognitive function in older adults with mild cognitive impairment or dementia: A meta-analysis. Ageing Res Rev. 2017;40:75–83. https://doi.org/10.1016/j.arr.2017.09.003.CrossRefPubMed

24.

Khan F, Ng L, Turner-Stokes L. Effectiveness of vocational rehabilitation intervention on the return to work and employment of persons with multiple sclerosis. Cochrane Database Syst Rev. 2009;2009(1):CD007256. https://doi.org/10.1002/14651858.CD007256.pub2.CrossRefPubMedPubMedCentral

25.

Meide HVD, Gorp DV, Van Der Hiele K, Visser L. “Always looking for a new balance”: toward an understanding of what it takes to continue working while being diagnosed with relapsing-remitting multiple sclerosis. Disabil Rehabil. 2018;40(21):2545–52. https://doi.org/10.1080/09638288.2017.1342278.CrossRefPubMed

26.

van der Hiele K, van Gorp DA, Heerings MA, van Lieshout I, Jongen PJ, Reneman MF, et al. The MS@Work study: a 3-year prospective observational study on factors involved with work participation in patients with relapsing-remitting Multiple Sclerosis. BMC Neurol. 2015;15:134. https://doi.org/10.1186/s12883-015-0375-4.CrossRefPubMedPubMedCentral

27.

Uitdehaag B, Kobelt G, Berg J, Capsa D, Dalén J. New insights into the burden and costs of multiple sclerosis in Europe: Results for the Netherlands. Mult Scler J. 2017;23(2_suppl):117–29. https://doi.org/10.1177/1352458517708663.CrossRef

28.

Boot CRL, van den Broek-van Lieshout IJ, van der Gulden JWJ. Werken hangt samen met de kwaliteit van leven bij mensen met multiple sclerose. TBV - Tijdschrift voor Bedrijfs- en Verzekeringsgeneeskunde. 2009;17(10):435–9. https://doi.org/10.1007/BF03081313.CrossRef

29.

Raad S-E. Werk: van belang voor iedereen - Een advies over werken met een chronische ziekte. 2016 ed. Sociaal-Economische Raad. 2016. p. 178. https://www.ser.nl/nl/publicaties/werken-chronische-ziekte. ISBN 978-94-6134-078-8.

30.

Bosma AR, Boot CRL, De Maaker M, Boeije HR, Schoonmade LJ, Anema JR, et al. Exploring self-control of workers with a chronic condition: a qualitative synthesis. Eur J Work Organ Psy. 2019;28(5):653–68. https://doi.org/10.1080/1359432X.2019.1631801.CrossRef

31.

Waskowiak PT, de Jong BA, Uitdehaag BMJ, Saddal SRD, Aarts J, et al. Don’t be late! Timely identification of cognitive impairment in people with multiple sclerosis: a study protocol. BMC Neurology. 2024. https://doi.org/10.1186/s12883-023-03495-x.

32.

Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162–73. https://doi.org/10.1016/S1474-4422(17)30470-2.CrossRefPubMed

33.

Benedict RH, Cookfair D, Gavett R, Gunther M, Munschauer F, Garg N, et al. Validity of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS). J Int Neuropsychol Soc. 2006;12(4):549–58.CrossRefPubMed

34.

Goghari VM, Lawlor-Savage L. Comparison of cognitive change after working memory training and logic and planning training in healthy older adults. Front Aging Neurosci. 2017;9:39. https://doi.org/10.3389/fnagi.2017.00039.CrossRefPubMedPubMedCentral

35.

van Balkom TD, Berendse HW, van der Werf YD, Twisk JWR, Peeters CFW, Hoogendoorn AW, et al. Effect of eight-week online cognitive training in Parkinson’s disease: A double-blind, randomized, controlled trial. Parkinsonism Relat Disord. 2022;96:80–7. https://doi.org/10.1016/j.parkreldis.2022.02.018.CrossRefPubMed

36.

van Balkom TD, van den Heuvel OA, Berendse HW, van der Werf YD, Hagen RH, Berk T, et al. Long-term effects of cognitive training in Parkinson’s disease: A randomized, controlled trial. Clin Park Relat Disord. 2023;9:100204. https://doi.org/10.1016/j.prdoa.2023.100204.CrossRefPubMedPubMedCentral

37.

van de Ven RM, Buitenweg JI, Schmand B, Veltman DJ, Aaronson JA, Nijboer TC, et al. Brain training improves recovery after stroke but waiting list improves equally: A multicenter randomized controlled trial of a computer-based cognitive flexibility training. PLoS One. 2017;12(3):e0172993. https://doi.org/10.1371/journal.pone.0172993.CrossRefPubMedPubMedCentral

38.

van Gorp DAM, van der Klink JJL, Abma FI, Jongen PJ, van Lieshout I, Arnoldus EPJ, et al. The capability set for work - correlates of sustainable employability in workers with multiple sclerosis. Health Qual Life Outcomes. 2018;16(1):113. https://doi.org/10.1186/s12955-018-0942-7.CrossRefPubMedPubMedCentral

39.

Abma FI, Brouwer S, de Vries HJ, Arends I, Robroek SJW, Cuijpers MPJ, et al. The capability set for work: development and validation of a new questionnaire. Scand J Work Environ Health. 2016;42(1):34–42. https://doi.org/10.5271/sjweh.3532.CrossRefPubMed

40.

Huysmans MS, Schaafsma FG, Viester L, Anema JR. Multidisciplinaire leidraad participatieve aanpak op de werkplek.: Made possible with ZonMW VIMP financing (projectnr. 208040001). VU medisch centrum Amsterdam. 2015.

41.

Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30(6):473–83.CrossRefPubMed

42.

Vickrey BG, Hays RD, Harooni R, Myers LW, Ellison GW. A health-related quality of life measure for multiple sclerosis. Qual Life Res. 1995;4(3):187–206. https://doi.org/10.1007/BF02260859.CrossRefPubMed

43.

Benedict RH, Cox D, Thompson LL, Foley F, Weinstock-Guttman B, Munschauer F. Reliable screening for neuropsychological impairment in multiple sclerosis. Mult Scler. 2004;10(6):675–8. https://doi.org/10.1191/1352458504ms1098oa.CrossRefPubMed

44.

Schmand B, Groenink SC, van den Dungen M. Letter fluency: psychometric properties and Dutch normative data. Tijdschr Gerontol Geriatr. 2008;39(2):64–76. https://doi.org/10.1007/BF03078128.CrossRefPubMed

45.

Benton AL, Sivan AB, Hamsher K, Varney NR, Spreen O. Contributions to Neuropsychological Assessment. 2nd ed. New York: Oxford University Press; 1994.

46.

Woods SP, Delis DC, Scott JC, Kramer JH, Holdnack JA. The California Verbal Learning Test–second edition: test-retest reliability, practice effects, and reliable change indices for the standard and alternate forms. Arch Clin Neuropsychol. 2006;21(5):413–20. https://doi.org/10.1016/j.acn.2006.06.002.CrossRefPubMed

47.

Delis D, Kaplan E, Kramer J, Deth R, Kuznetsova A, Waly M, et al. Neuropsychological assessment of learning and memory. Cortex. 1989;10(3):308–17.

48.

Mulder JL, Dekker R, Dekker PH. Verbale Leer en Geheugen Test. London: Pearson Assessment; 1996.

49.

Benedict RHB, Schretlen D, Groninger L, Dobraski M, Shpritz B. Revision of the Brief Visuospatial Memory Test: Studies of normal performance, reliability, and validity. Psychol Assess. 1996;8:8.CrossRef

50.

Gronwall DM. Paced auditory serial-addition task: a measure of recovery from concussion. Percept Mot Skills. 1977;44(2):367–73.CrossRefPubMed

51.

Smith A. Symbol digit modalities test: Manual. Los Angeles: Western Psychological Services; 1982.

52.

Delis DC, Kramer JH, Kaplan E, Holdnack J. Reliability and validity of the Delis-Kaplan Executive Function System: an update. J Int Neuropsychol Soc. 2004;10(2):301–3. https://doi.org/10.1017/S1355617704102191.CrossRefPubMed

53.

Rao SM. A manual for the brief repeatable battery of neuropsychological tests in multiple sclerosis. Milwaukee: Medical College of Wisconsin; 1990. p. 1696.

54.

Schagen S, Schmand B, de Sterke S, Lindeboom J. Amsterdam Short-Term Memory test: a new procedure for the detection of feigned memory deficits. J Clin Exp Neuropsychol. 1997;19(1):43–51. https://doi.org/10.1080/01688639708403835.CrossRefPubMed

55.

Rey A. L’examin clinique en psychologie Paris. France: Presses Universitaires de France; 1958.

56.

Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and activity impairment instrument. Pharmacoeconomics. 1993;4(5):353–65.CrossRefPubMed

57.

Honan CA, Brown RF, Hine DW. The multiple sclerosis work difficulties questionnaire (MSWDQ): development of a shortened scale. Disabil Rehabil. 2014;36(8):635–41. https://doi.org/10.3109/09638288.2013.805258.CrossRefPubMed

58.

van Egmond E, van Gorp D, Honan C, Heerings M, Jongen P, van der Klink J, et al. A Dutch validation study of the multiple sclerosis work difficulties questionnaire in relapsing remitting multiple sclerosis. Disabil Rehabil. 2019:1–10. https://doi.org/10.1080/09638288.2019.1686072.

59.

de Jong M, Tamminga SJ, van Es RJJ, Frings-Dresen MHW, de Boer A. The quality of working life questionnaire for cancer survivors (QWLQ-CS): factorial structure, internal consistency, construct validity and reproducibility. BMC Cancer. 2018;18(1):66. https://doi.org/10.1186/s12885-017-3966-1.CrossRefPubMedPubMedCentral

60.

Bosma AL, Ouwerkerk W, Gunal M, Hyseni AM, Arents BWM, Gerbens LAA, et al. Work ability and quality of working life in atopic dermatitis patients treated with dupilumab. J Dermatol. 2021;48(9):1305–14. https://doi.org/10.1111/1346-8138.15939.CrossRefPubMedPubMedCentral

61.

de Wit M, Zijlstra HP, Hulshof CTJ, van der Burg-Vermeulen SJ, de Boer A. The effect of the Progressive Goal Attainment Program on cognitions, perceptions, and work participation of workers with chronic health problems: study protocol for a randomized controlled trial. Trials. 2022;23(1):765. https://doi.org/10.1186/s13063-022-06698-8.CrossRefPubMedPubMedCentral

62.

van Gennep S, de Boer NKH, Gielen ME, Rietdijk ST, Gecse KB, Ponsioen CY, et al. Impaired quality of working life in inflammatory bowel disease patients. Dig Dis Sci. 2021;66(9):2916–24. https://doi.org/10.1007/s10620-020-06647-y.CrossRefPubMed

63.

Steenwijk MD, Pouwels PJ, Daams M, van Dalen JW, Caan MW, Richard E, et al. Accurate white matter lesion segmentation by k nearest neighbor classification with tissue type priors (kNN-TTPs). Neuroimage Clin. 2013;3:462–9. https://doi.org/10.1016/j.nicl.2013.10.003.CrossRefPubMedPubMedCentral

64.

Chard DT, Jackson JS, Miller DH, Wheeler-Kingshott CA. Reducing the impact of white matter lesions on automated measures of brain gray and white matter volumes. J Magn Reson Imaging. 2010;32(1):223–8. https://doi.org/10.1002/jmri.22214.CrossRefPubMed

65.

Patenaude B, Smith SM, Kennedy DN, Jenkinson M. A Bayesian model of shape and appearance for subcortical brain segmentation. Neuroimage. 2011;56(3):907–22. https://doi.org/10.1016/j.neuroimage.2011.02.046.CrossRefPubMed

66.

Barkhof F, Calabresi PA, Miller DH, Reingold SC. Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol. 2009;5(5):256–66. https://doi.org/10.1038/nrneurol.2009.41.CrossRefPubMed

67.

Hulst HE, Steenwijk MD, Versteeg A, Pouwels PJ, Vrenken H, Uitdehaag BM, et al. Cognitive impairment in MS: impact of white matter integrity, gray matter volume, and lesions. Neurology. 2013;80(11):1025–32. https://doi.org/10.1212/WNL.0b013e31828726cc.CrossRefPubMed

68.

Kiljan S, Meijer KA, Steenwijk MD, Pouwels PJW, Schoonheim MM, Schenk GJ, et al. Structural network topology relates to tissue properties in multiple sclerosis. J Neurol. 2019;266(1):212–22. https://doi.org/10.1007/s00415-018-9130-2.CrossRefPubMed

69.

Meijer KA, Cercignani M, Muhlert N, Sethi V, Chard D, Geurts JJ, et al. Patterns of white matter damage are non-random and associated with cognitive function in secondary progressive multiple sclerosis. Neuroimage Clin. 2016;12:123–31. https://doi.org/10.1016/j.nicl.2016.06.009.CrossRefPubMedPubMedCentral

70.

Meijer KA, Muhlert N, Cercignani M, Sethi V, Ron MA, Thompson AJ, et al. White matter tract abnormalities are associated with cognitive dysfunction in secondary progressive multiple sclerosis. Mult Scler. 2016;22(11):1429–37. https://doi.org/10.1177/1352458515622694.CrossRefPubMed

71.

Finke C, Schlichting J, Papazoglou S, Scheel M, Freing A, Soemmer C, et al. Altered basal ganglia functional connectivity in multiple sclerosis patients with fatigue. Mult Scler. 2015;21(7):925–34. https://doi.org/10.1177/1352458514555784.CrossRefPubMed

72.

Liu Y, Duan Y, Dong H, Barkhof F, Li K, Shu N. Disrupted module efficiency of structural and functional brain connectomes in clinically isolated syndrome and multiple sclerosis. Front Hum Neurosci. 2018;12:138. https://doi.org/10.3389/fnhum.2018.00138.CrossRefPubMedPubMedCentral

73.

Meijer KA, Eijlers AJC, Geurts JJG, Schoonheim MM. Staging of cortical and deep grey matter functional connectivity changes in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2018;89(2):205–10. https://doi.org/10.1136/jnnp-2017-316329.CrossRefPubMed

74.

Bassett DS, Sporns O. Network neuroscience. Nat Neurosci. 2017;20(3):353–64. https://doi.org/10.1038/nn.4502.CrossRefPubMedPubMedCentral

75.

Meijer KA, Eijlers AJC, Douw L, Uitdehaag BMJ, Barkhof F, Geurts JJG, et al. Increased connectivity of hub networks and cognitive impairment in multiple sclerosis. Neurology. 2017;88(22):2107–14. https://doi.org/10.1212/WNL.0000000000003982.CrossRefPubMed

76.

Strik M, Chard DT, Dekker I, Meijer KA, Eijlers AJ, Pardini M, et al. Increased functional sensorimotor network efficiency relates to disability in multiple sclerosis. Mult Scler. 2021;27(9):1364–73. https://doi.org/10.1177/1352458520966292.CrossRefPubMed

77.

Schoonheim MM, Geurts J, Wiebenga OT, De Munck JC, Polman CH, Stam CJ, et al. Changes in functional network centrality underlie cognitive dysfunction and physical disability in multiple sclerosis. Mult Scler. 2014;20(8):1058–65. https://doi.org/10.1177/1352458513516892.CrossRefPubMed

78.

Vercoulen JH, Swanink CM, Fennis JF, Galama JM, van der Meer JW, Bleijenberg G. Dimensional assessment of chronic fatigue syndrome. J Psychosom Res. 1994;38(5):383–92.CrossRefPubMed

79.

Rietberg MB, Van Wegen EE, Kwakkel G. Measuring fatigue in patients with multiple sclerosis: reproducibility, responsiveness and concurrent validity of three Dutch self-report questionnaires. Disabil Rehabil. 2010;32(22):1870–6. https://doi.org/10.3109/09638281003734458.CrossRefPubMed

80.

Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361–70.CrossRefPubMed

81.

Honarmand K, Feinstein A. Validation of the hospital anxiety and depression scale for use with multiple sclerosis patients. Mult Scler. 2009;15(12):1518–24. https://doi.org/10.1177/1352458509347150. 1352458509347150 [pii].CrossRefPubMed

82.

Connor KM. Assessment of resilience in the aftermath of trauma. J Clin Psychiatry. 2006;67(Suppl 2):46–9.PubMed

83.

Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983;24(4):385–96.CrossRefPubMed

84.

Wu SM, Amtmann D. Psychometric Evaluation of the Perceived Stress Scale in Multiple Sclerosis. ISRN Rehabilitation. 2013;2013:608356. https://doi.org/10.1155/2013/608356.CrossRef

85.

Van Doesum NJ, Van Lange DA, Van Lange PA. Social mindfulness: skill and will to navigate the social world. J Pers Soc Psychol. 2013;105(1):86–103. https://doi.org/10.1037/a0032540.CrossRefPubMed

86.

Hahn EA, Devellis RF, Bode RK, Garcia SF, Castel LD, Eisen SV, et al. Measuring social health in the patient-reported outcomes measurement information system (PROMIS): item bank development and testing. Qual Life Res. 2010;19(7):1035–44. https://doi.org/10.1007/s11136-010-9654-0.CrossRefPubMedPubMedCentral

87.

Bouwmans C, Krol M, Severens H, Koopmanschap M, Brouwer W, Hakkaart-van RL. The iMTA productivity cost questionnaire: a standardized instrument for measuring and valuing health-related productivity losses. Value Health. 2015;18(6):753–8. https://doi.org/10.1016/j.jval.2015.05.009.CrossRefPubMed

88.

www.imta.nl, Bouwmans C, Koopmanschap M, Krol M, Severens H, Brouwer W. Handleiding iMTA medical cost questionnaire (iMCQ). 2013.

89.

Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20(10):1727–36. https://doi.org/10.1007/s11136-011-9903-x.CrossRefPubMedPubMedCentral

90.

Versteegh MM, Vermeulen KM, Evers SM, De Wit GA, Prenger R, Stolk EA. Dutch Tariff for the Five-Level Version of EQ-5D. Value Health. 2016;19(4):343–52. https://doi.org/10.1016/j.jval.2016.01.003.CrossRef

91.

Franchignoni F, Horak F, Godi M, Nardone A, Giordano A. Using psychometric techniques to improve the balance evaluation systems test: the mini-BESTest. J Rehabil Med. 2010;42(4):323–31. https://doi.org/10.2340/16501977-0537.CrossRefPubMed

92.

Godi M, Franchignoni F, Caligari M, Giordano A, Turcato AM, Nardone A. Comparison of reliability, validity, and responsiveness of the mini-BESTest and Berg Balance Scale in patients with balance disorders. Phys Ther. 2013;93(2):158–67. https://doi.org/10.2522/ptj.20120171.CrossRefPubMed

93.

Motl RW, Cohen JA, Benedict R, Phillips G, LaRocca N, Hudson LD, et al. Validity of the timed 25-foot walk as an ambulatory performance outcome measure for multiple sclerosis. Mult Scler. 2017;23(5):704–10. https://doi.org/10.1177/1352458517690823.CrossRefPubMedPubMedCentral

94.

Cohen JA, Krishnan AV, Goodman AD, Potts J, Wang P, Havrdova E, et al. The clinical meaning of walking speed as measured by the timed 25-foot walk in patients with multiple sclerosis. JAMA Neurol. 2014;71(11):1386–93. https://doi.org/10.1001/jamaneurol.2014.1895.CrossRefPubMed

95.

Karanfil E, Salci Y, Balkan AF, Sutcu G, Tuncer A. Reliability and validity of the incremental shuttle walk test in patients with fully ambulatory multiple sclerosis. Mult Scler Relat Disord. 2023;70:104522. https://doi.org/10.1016/j.msard.2023.104522.CrossRefPubMed

96.

Singh SJ, Morgan MD, Scott S, Walters D, Hardman AE. Development of a shuttle walking test of disability in patients with chronic airways obstruction. Thorax. 1992;47(12):1019–24. https://doi.org/10.1136/thx.47.12.1019.CrossRefPubMedPubMedCentral

97.

Roberts HC, Denison HJ, Martin HJ, Patel HP, Syddall H, Cooper C, et al. A review of the measurement of grip strength in clinical and epidemiological studies: towards a standardised approach. Age Ageing. 2011;40(4):423–9. https://doi.org/10.1093/ageing/afr051.CrossRefPubMed

98.

Feys P, Lamers I, Francis G, Benedict R, Phillips G, LaRocca N, et al. The Nine-Hole Peg Test as a manual dexterity performance measure for multiple sclerosis. Mult Scler. 2017;23(5):711–20. https://doi.org/10.1177/1352458517690824.CrossRefPubMedPubMedCentral

99.

Gallus J, Mathiowetz V. Test-retest reliability of the Purdue Pegboard for persons with multiple sclerosis. Am J Occup Ther. 2003;57(1):108–11. https://doi.org/10.5014/ajot.57.1.108.CrossRefPubMed

100.

Lamers I, Kelchtermans S, Baert I, Feys P. Upper limb assessment in multiple sclerosis: a systematic review of outcome measures and their psychometric properties. Arch Phys Med Rehabil. 2014;95(6):1184–200. https://doi.org/10.1016/j.apmr.2014.02.023.CrossRefPubMed

101.

Kiresuk TJ, Sherman RE. Goal attainment scaling: A general method for evaluating comprehensive community mental health programs. Community Ment Health J. 1968;4(6):443–53. https://doi.org/10.1007/BF01530764.CrossRefPubMed

102.

Amato MP, Ponziani G, Siracusa G, Sorbi S. Cognitive dysfunction in early-onset multiple sclerosis: a reappraisal after 10 years. Arch Neurol. 2001;58(10):1602–6 noc10005 [pii].CrossRefPubMed

103.

Jacobson NS, Truax P. Clinical significance: a statistical approach to defining meaningful change in psychotherapy research. J Consult Clin Psychol. 1991;59(1):12–9. https://doi.org/10.1037//0022-006x.59.1.12.CrossRefPubMed

104.

Baron RM, Kenny DA. The moderator–mediator variable distinction in social psychological research: Conceptual, strategic, and statistical considerations. J Pers Soc Psychol. 1986;51(6):1173–82. https://doi.org/10.1037/0022-3514.51.6.1173.CrossRefPubMed

105.

White IR, Royston P, Wood AM. Multiple imputation using chained equations: Issues and guidance for practice. Stat Med. 2011;30(4):377–99. https://doi.org/10.1002/sim.4067.CrossRefPubMed

106.

Braun V, Clarke V. Thematic analysis : a practical guide. London: SAGE Publications Ltd; 2022. xxxiv, 338 pages p.CrossRef

Title: Don’t be late! Postponing cognitive decline and preventing early unemployment in people with multiple sclerosis: a study protocol
Authors: Jip Aarts
Shalina R. D. Saddal
Judith E. Bosmans
Vincent de Groot
Brigit A. de Jong
Martin Klein
Marit F. L. Ruitenberg
Frederieke G. Schaafsma
Esther C. F. Schippers
Menno M. Schoonheim
Bernard M. J. Uitdehaag
Sabina van der Veen
Pauline T. Waskowiak
Guy A. M. Widdershoven
Karin van der Hiele
Hanneke E. Hulst
on behalf of the Don’t be late! consortium
Publication date: 01-12-2024
Publisher: BioMed Central
Keyword: Multiple Sclerosis
Published in: BMC Neurology / Issue 1/2024
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/s12883-023-03513-y

At a glance: The STEP trials

Springer Medicine

Don’t be late! Postponing cognitive decline and preventing early unemployment in people with multiple sclerosis: a study protocol

Abstract

Background

Aims

Methods

Discussion

Trial registration

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Aims

Methods

Discussion

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2024

MRI-based clinical-radiomics nomogram to predict early neurological deterioration in isolated acute pontine infarction: a two-center study in Northeast China

Cerebral blood flow changes in maintenance hemodialysis patients with restless legs syndrome and their clinical significance:a cross-sectional case-control study

A case of NMDAR Encephalitis with muscular pain as the main presentation

Hand knob sign in osmotic demyelinating syndrome

Study protocol: exercise training for treating major depressive disorder in multiple sclerosis

Does exercise improve sleep in Parkinson’s disease?