Skip to main content

Advertisement

Log in

Treating MS After 50: the Role of Age in Therapeutic Decision-Making

  • Multiple Sclerosis and Related Disorders (J Graves, Section Editor)
  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Abstract

Purpose of Review

This review presents the latest evidence available regarding treating patients with MS over age 50. This includes what is known about disease-modifying therapies, symptomatic interventions, and comorbid conditions that influence disease management in older patients.

Recent Findings

There is limited clinical trial data for patients over age 50. Recent meta-analyses of clinical trials of immunomodulatory therapies indicate there is minimal efficacy after age 50 on disability progression. Additionally, immunosenescent changes increase risks of adverse effects in older adults. Advances in understanding disease progression offer new treatment targets. Fortunately, emerging therapies on progression and repair have included older patients and will hopefully lead to neurodegenerative therapies and allow tailored treatments based on age.

Summary

While data is limited to support the use of immunomodulatory therapies in older patients, treatment decisions should be made on an individual basis based on disease activity, patient-specific factors, and patient preference. It is also important to focus on symptoms and comorbidities that affect quality of life.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Kingwell E, Zhu F, Marrie RA, Fisk JD, Wolfson C, Warren S, et al. High incidence and increasing prevalence of multiple sclerosis in British Columbia, Canada: findings from over two decades (1991–2010). J Neurol. 2015;262:2352–63.

    PubMed  PubMed Central  Google Scholar 

  2. Rotstein DL, Chen H, Wilton AS, Kwong JC, Marrie RA, Gozdyra P, et al. Temporal trends in multiple sclerosis prevalence and incidence in a large population. Neurology. 2018;90:e1435–41.

    PubMed  Google Scholar 

  3. • Wallin MT, Culpepper WJ, Campbell JD, et al. The prevalence of MS in the United States: a population-based estimate using health claims data. Neurology 2019; 92: e1029–e1040. This study provides updates in prevalence of MS in the US.

  4. Mahad DH, Trapp BD, Lassmann H. Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol. 2015;14:183–93.

    CAS  PubMed  Google Scholar 

  5. •• Sun M, McDonald SJ, Brady RD, et al. The need to incorporate aged animals into the preclinical modeling of neurological conditions. Neurosci Biobehav Rev 2020; 109: 114–128. This review highlights the biological changes of age and impact on neurological disorders and provides rationale for the need of older animals in pre-clinical trials to improve success of translation into human trials.

  6. Tutuncu M, Tang J, Zeid NA, Kale N, Crusan DJ, Atkinson EJ, et al. Onset of progressive phase is an age-dependent clinical milestone in multiple sclerosis. Mult Scler J. 2013;19:188–98.

    Google Scholar 

  7. Deleidi M, Jäggle M, Rubino G. Immune aging, dysmetabolism, and inflammation in neurological diseases. Front Neurosci; 9. Epub ahead of print 3 June 2015. https://doi.org/10.3389/fnins.2015.00172.

  8. • Zhang T, Tremlett H, Zhu F, et al. Effects of physical comorbidities on disability progression in multiple sclerosis. Neurology 2018; 90: e419–e427. This study highlights the impact of comorbidities in disability progression in MS.

  9. • McKay KA, Tremlett H, Fisk JD, et al. Psychiatric comorbidity is associated with disability progression in multiple sclerosis. Neurology 2018; 90: e1316–e1323. This study highlights how psychiatric comorbidities influence disability progression in MS.

  10. Dhib-Jalbut S, Marks S. Interferon-β mechanisms of action in multiple sclerosis. Neurology. 2010;74:S17–24.

    CAS  PubMed  Google Scholar 

  11. Lampl C, Nagl S, Arnason B, Comi G, O′Connor P, Cook S, et al. Efficacy and safety of interferon beta-1b sc in older RRMS patients—a posthoc analysis of the BEYOND study. J Neurol. 2013;260:1838–45.

    CAS  PubMed  Google Scholar 

  12. Newman S, Mao-Draayer Y, Blitz K, et al. ADVANCE: peginterferon beta-1a patients 50 years and older age subgroup analysis and effect on clinical and radiologic outcomes. Int J MS Care. 2019;21(S1):34.

    Google Scholar 

  13. Shirani A, Zhao Y, Petkau J, Gustafson P, Karim ME, Evans C, et al. Multiple sclerosis in older adults: the clinical profile and impact of interferon beta treatment. Biomed Res Int. 2015;2015:1–11.

    Google Scholar 

  14. Claussen MC, Korn T. Immune mechanisms of new therapeutic strategies in MS — teriflunomide. Clin Immunol. 2012;142:49–56.

    CAS  PubMed  Google Scholar 

  15. Oh J, Vukusic S, Tiel-Wilck K, et al. Efficacy and safety of teriflunomide in patients of different ages: analysis of pooled clinical trials and real-world data. Int J MS Care. 2019;21(S1):29.

    Google Scholar 

  16. Linker RA, Gold R. Dimethyl fumarate for treatment of multiple sclerosis: mechanism of action, effectiveness, and side effects. Curr Neurol Neurosci Rep. 2013;13:394.

    PubMed  Google Scholar 

  17. Mao-Draayer Y, Giles K, Balashov K, et al. Safety and effectiveness of delayed-release dimethyl Fumarate in patients ≥ 55 years enrolled in the phase IV ESTEEM Study. Int J MS Care; 21(S1).

  18. Cohen JA, Chun J. Mechanisms of fingolimod’s efficacy and adverse effects in multiple sclerosis. Ann Neurol. 2011;69:759–77.

    CAS  PubMed  Google Scholar 

  19. Hua LH, Bar-Or A, Lublin FD, et al. Analyses of the effect of baseline age on the efficacy and safety of siponimod in patients with active secondary progressive multiple sclerosis from the EXPAND Study. Int J MS Care. 2020;22(S2):31.

    Google Scholar 

  20. Hauser SL. The Charcot Lecture | beating MS: a story of B cells, with twists and turns. Mult Scler J. 2014;1352458514561911.

  21. Hawker K, O’Connor P, Freedman MS, et al. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol. 2009;66:460–71.

    CAS  PubMed  Google Scholar 

  22. Wolinsky JS, Montalban X, Hauser SL, et al. Prespecified subgroup analyses of ocrelizumab efficacy in patients with primary progressive multiple sclerosis from the phase 3 ORATORIO study. Int J MS Care. 2018;20(S1):32.

    Google Scholar 

  23. Rice GP, Hartung H-P, Calabresi PA. Anti-α4 integrin therapy for multiple sclerosis mechanisms and rationale. Neurology. 2005;64:1336–42.

    CAS  PubMed  Google Scholar 

  24. Matell H, Lycke J, Svenningsson A, Holmén C, Khademi M, Hillert J, et al. Age-dependent effects on the treatment response of natalizumab in MS patients. Mult Scler J. 2015;21:48–56.

    CAS  Google Scholar 

  25. Giovannoni G. Cladribine to treat relapsing forms of multiple sclerosis. Neurotherapeutics. 2017;14:874–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Giovannoni G., Rammohan K, Cook S, et al. Efficacy of cladribine tablets 3.5 mg/kg in patients ≤50 and >50 years of age with relapsing-remitting multiple sclerosis (RRMS): a post hoc analysis from CLARITY. Eur J Neurol 2018; 25(S2): 331.

  27. Hartung H-P, Aktas O, Boyko AN. Alemtuzumab: a new therapy for active relapsing-remitting multiple sclerosis. Mult Scler. 2015;21:22–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Bass AD, Arroyo R, Boster A, et al. Alemtuzumab improves clinical and magnetic resonance imaging outcomes in relapsing-remitting multiple sclerosis patients across age groups: CARE-MS I and II 8-year follow-up. Int J MS Care. 2019;21(S1):20.

    Google Scholar 

  29. Varkony H, Weinstein V, Klinger E, Sterling J, Cooperman H, Komlosh T, et al. The glatiramoid class of immunomodulator drugs. Expert Opin Pharmacother. 2009;10:657–68.

    CAS  PubMed  Google Scholar 

  30. Wolinsky JS, Narayana PA, O’Connor P, et al. Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol. 2007;61:14–24.

    CAS  PubMed  Google Scholar 

  31. Lublin F, Miller DH, Freedman MS, Cree BAC, Wolinsky JS, Weiner H, et al. Oral fingolimod in primary progressive multiple sclerosis (INFORMS): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Lond Engl. 2016;387:1075–84.

    CAS  Google Scholar 

  32. European Study Group on interferon beta-1b in secondary progressive MS. Lancet Lond Engl 1998; 352: 1491–1497, Placebo-controlled multicentre randomised trial of interferon β-1b in treatment of secondary progressive multiple sclerosis.

  33. Secondary Progressive Efficacy Clinical Trial of Recombinant Interferon-beta-1a in MS (SPECTRIMS) Study Group. Randomized controlled trial of interferon- beta-1a in secondary progressive MS: clinical results. Neurology 2001; 56: 1496–1504.

  34. Panitch H, Miller A, Paty D, Weinshenker B, North American Study Group on Interferon beta-1b in Secondary Progressive MS. Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study. Neurology. 2004;63:1788–95.

    PubMed  Google Scholar 

  35. Kapoor R, Ho P-R, Campbell N, Chang I, Deykin A, Forrestal F, et al. Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND): a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension. Lancet Neurol. 2018;17:405–15.

    CAS  PubMed  Google Scholar 

  36. Montalban X, Hauser SL, Kappos L, Arnold DL, Bar-Or A, Comi G, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376:209–20.

    CAS  PubMed  Google Scholar 

  37. Kappos L, Bar-Or A, Cree BAC, Fox RJ, Giovannoni G, Gold R, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet. 2018;391:1263–73.

    CAS  PubMed  Google Scholar 

  38. Signori A, Schiavetti I, Gallo F, Sormani MP. Subgroups of multiple sclerosis patients with larger treatment benefits: a meta-analysis of randomized trials. Eur J Neurol. 2015;22:960–6.

    CAS  PubMed  Google Scholar 

  39. •• Weideman AM, Tapia-Maltos MA, Johnson K, et al. Meta-analysis of the age-dependent efficacy of multiple sclerosis treatments. Front Neurol 2017; 8: 577. This is a large meta-analysis of 38 pivotal MS clinical trials covering most DMTs, which utilizes linear regression modeling of disability outcomes as a function of age to demonstrate reduced efficacy of DMTs in patients over age 53.

  40. Grebenciucova E, Berger JR. Immunosenescence: the role of aging in the predisposition to neuro-infectious complications arising from the treatment of multiple sclerosis. Curr Neurol Neurosci Rep. 2017;17:61.

    PubMed  Google Scholar 

  41. Schoevaerdts D, Sibille F-X, Gavazzi G. Infections in the older population: what do we know? Aging Clin Exp Res. Epub ahead of print 26 October 2019. https://doi.org/10.1007/s40520-019-01375-4.

  42. Wijnands JMA, Zhu F, Kingwell E, Fisk JD, Evans C, Marrie RA, et al. Disease-modifying drugs for multiple sclerosis and infection risk: a cohort study. J Neurol Neurosurg Psychiatry. 2018;89:1050–6.

    PubMed  Google Scholar 

  43. • Luna G, Alping P, Burman J, et al. Infection risks among patients with multiple sclerosis treated with fingolimod, natalizumab, rituximab, and injectable therapies. JAMA Neurol. Epub ahead of print 7 October 2019. DOI: https://doi.org/10.1001/jamaneurol.2019.3365. This is a large study of infection risks of disease modifying therapies to better understand risk benefit ratio in older patients with MS.

  44. Wijnands JM, Kingwell E, Zhu F, et al. Infection-related health care utilization among people with and without multiple sclerosis. Mult Scler J. 2017;23:1506–16.

    Google Scholar 

  45. Prosperini L, Scarpazza C, Imberti L, et al. Age as a risk factor for early onset of natalizumab-related progressive multifocal leukoencephalopathy. J Neuro-Oncol. 2017;23:742–9.

    CAS  Google Scholar 

  46. Gieselbach R-J, Muller-Hansma AH, Wijburg MT, de Bruin-Weller MS, van Oosten BW, Nieuwkamp DJ, et al. Progressive multifocal leukoencephalopathy in patients treated with fumaric acid esters: a review of 19 cases. J Neurol. 2017;264:1155–64.

    CAS  PubMed  Google Scholar 

  47. Longbrake EE, Naismith RT, Parks BJ, et al. Dimethyl fumarate-associated lymphopenia: Risk factors and clinical significance. Mult Scler J - Exp Transl Clin; 1. Epub ahead of print December 2015. https://doi.org/10.1177/2055217315596994.

  48. Briner M, Bagnoud M, Miclea A, et al. Time course of lymphocyte repopulation after dimethyl fumarate-induced grade 3 lymphopenia: contribution of patient age. Ther Adv Neurol Disord. 2019;12:1756286419843450.

    PubMed  PubMed Central  Google Scholar 

  49. Diebold M, Altersberger V, Décard BF, Kappos L, Derfuss T, Lorscheider J. A case of progressive multifocal leukoencephalopathy under dimethyl fumarate treatment without severe lymphopenia or immunosenescence. Mult Scler J. 2019;25:1682–5.

    Google Scholar 

  50. Berger JR, Cree BA, Greenberg B, Hemmer B, Ward BJ, Dong VM, et al. Progressive multifocal leukoencephalopathy after fingolimod treatment. Neurology. 2018;90:e1815–21.

    PubMed  PubMed Central  Google Scholar 

  51. Grebenciucova E, Reder AT, Bernard JT. Immunologic mechanisms of fingolimod and the role of immunosenescence in the risk of cryptococcal infection: a case report and review of literature. Mult Scler Relat Disord. 2016;9:158–62.

    PubMed  Google Scholar 

  52. Gilenya(R) [package insert]. Stein, Switzerland: Novartis Pharma Stein AG, https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/gilenya.pdf (2010, accessed 30 July 2017).

  53. Arvin AM, Wolinsky JS, Kappos L, et al. Varicella-zoster virus infections in patients treated with fingolimod: risk assessment and consensus recommendations for management. JAMA Neurol. Epub ahead of print 24 November 2014. https://doi.org/10.1001/jamaneurol.2014.3065.

  54. Derfuss T, Weber MS, Hughes R, et al. Serum immunoglobulin levels and risk of serious infections in the pivotal phase III trials of ocrelizumab in multiple sclerosis and their open-label extensions. Mult Scler. 2019;25(S2):20.

    Google Scholar 

  55. Barmettler S, Ong M-S, Farmer JR, Choi H, Walter J. Association of immunoglobulin levels, infectious risk, and mortality with rituximab and hypogammaglobulinemia. JAMA Netw Open. 2018;1:e184169.

    PubMed  PubMed Central  Google Scholar 

  56. Cavalli G, Favalli EG. Biologic discontinuation strategies and outcomes in patients with rheumatoid arthritis. Expert Rev Clin Immunol. 2019;15:1313–22.

    CAS  PubMed  Google Scholar 

  57. Fautrel B, den Broeder AA. De-intensifying treatment in established rheumatoid arthritis (RA): why, how, when and in whom can DMARDs be tapered? Best Pract Res Clin Rheumatol. 2015;29:550–65.

    PubMed  Google Scholar 

  58. Lenert A, Lenert P. Tapering biologics in rheumatoid arthritis: a pragmatic approach for clinical practice. Clin Rheumatol. 2017;36:1–8.

    PubMed  Google Scholar 

  59. Hua LH, Fan TH, Conway D, Thompson N, Kinzy TG. Discontinuation of disease-modifying therapy in patients with multiple sclerosis over age 60. Mult Scler J. 2019;25:699–708.

    Google Scholar 

  60. Bsteh G, Feige J, Ehling R, et al. Discontinuation of disease-modifying therapies in multiple sclerosis–clinical outcome and prognostic factors. Mult Scler J. 2016;1352458516675751.

  61. Kister I, Spelman T, Alroughani R, Lechner-Scott J, Duquette P, Grand'Maison F, et al. Discontinuing disease-modifying therapy in MS after a prolonged relapse-free period: a propensity score-matched study. J Neurol Neurosurg Psychiatry. 2016;87:1133–7.

    PubMed  Google Scholar 

  62. Birnbaum G. Stopping disease-modifying therapy in nonrelapsing multiple sclerosis. Int J MS Care. 2017;19:11–4.

    PubMed  PubMed Central  Google Scholar 

  63. Klewer J, Pohlau D, Nippert I, et al. Problems reported by elderly patients with multiple sclerosis. J Neurosci Nurs Park Ridge. 2001;33:167–71.

    CAS  Google Scholar 

  64. Minden SL, Frankel D, Hadden LS, Srinath KP, Perloff JN. Disability in elderly people with multiple sclerosis: an analysis of baseline data from the Sonya Slifka Longitudinal Multiple Sclerosis Study. NeuroRehabilitation. 2004;19:55–67.

    PubMed  Google Scholar 

  65. Rønning OM, Tornes KD. Need for symptomatic management in advanced multiple sclerosis. Acta Neurol Scand. 2017;135:529–32.

    PubMed  Google Scholar 

  66. Lonergan R, Kinsella K, Fitzpatrick P, Duggan M, Jordan S, Bradley D, et al. Unmet needs of multiple sclerosis patients in the community. Mult Scler Relat Disord. 2015;4:144–50.

    PubMed  Google Scholar 

  67. Goodman AD, Brown TR, Krupp LB, Schapiro RT, Schwid SR, Cohen R, et al. Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet. 2009;373:732–8.

    CAS  PubMed  Google Scholar 

  68. Goodman AD, Brown TR, Schapiro RT, Klingler M, Cohen R, Blight AR. A pooled analysis of two phase 3 clinical trials of dalfampridine in patients with multiple sclerosis. Int J MS Care. 2014;16:153–60.

    PubMed  PubMed Central  Google Scholar 

  69. Bakirtzis C, Konstantinopoulou E, Langdon DW, Grigoriadou E, Minti F, Nikolaidis I, et al. Long-term effects of prolonged-release fampridine in cognitive function, fatigue, mood and quality of life of MS patients: the IGNITE study. J Neurol Sci. 2018;395:106–12.

    CAS  PubMed  Google Scholar 

  70. Broicher SD, Filli L, Geisseler O, Germann N, Zörner B, Brugger P, et al. Positive effects of fampridine on cognition, fatigue and depression in patients with multiple sclerosis over 2 years. J Neurol. 2018;265:1016–25.

    CAS  PubMed  Google Scholar 

  71. De Giglio L, De Luca F, Gurreri F, et al. Effect of dalfampridine on information processing speed impairment in multiple sclerosis. Neurology. 2019;93:e733–46.

    PubMed  Google Scholar 

  72. Kanhai KMS, Bijvank JAN, Wagenaar YL, et al. Treatment of internuclear ophthalmoparesis in multiple sclerosis with fampridine: a randomized double-blind, placebo-controlled cross-over trial. CNS Neurosci Ther. 2019;25:697–703.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Rodriguez-Leal FA, Haase R, Akgün K, et al. Nonwalking response to fampridine in patients with multiple sclerosis in a real-world setting. Ther Adv Chronic Dis. 2019;10:2040622319835136.

    PubMed  PubMed Central  Google Scholar 

  74. Valet M, Quoilin M, Lejeune T, Stoquart G, van Pesch V, el Sankari S, et al. Effects of fampridine in people with multiple sclerosis: a systematic review and meta-analysis. CNS Drugs. 2019;33:1087–99.

    CAS  PubMed  Google Scholar 

  75. Yerneni K, Nichols N, Burke JF, Traynelis VC, Tan LA. Surgical management of patients with coexistent multiple sclerosis and cervical stenosis: a systematic review and meta-analysis. J Clin Neurosci. 2019;65:77–82.

    PubMed  Google Scholar 

  76. Cotter J, Muhlert N, Talwar A, Granger K. Examining the effectiveness of acetylcholinesterase inhibitors and stimulant-based medications for cognitive dysfunction in multiple sclerosis: a systematic review and meta-analysis. Neurosci Biobehav Rev. 2018;86:99–107.

    CAS  PubMed  Google Scholar 

  77. Yang T, Wang L, Deng X, Yu G. Pharmacological treatments for fatigue in patients with multiple sclerosis: a systematic review and meta-analysis. J Neurol Sci. 2017;380:256–61.

    CAS  PubMed  Google Scholar 

  78. Thelen JM, Lynch SG, Bruce AS, Hancock LM, Bruce JM. Polypharmacy in multiple sclerosis: relationship with fatigue, perceived cognition, and objective cognitive performance. J Psychosom Res. 2014;76:400–4.

    PubMed  Google Scholar 

  79. Marrie RA, Cohen J, Stuve O, et al. A systematic review of the incidence and prevalence of comorbidity in multiple sclerosis: overview. Mult Scler J. 2015;1352458514564491.

  80. Marrie RA, Elliott L, Marriott J, Cossoy M, Blanchard J, Leung S, et al. Effect of comorbidity on mortality in multiple sclerosis. Neurology. 2015;85:240–7. https://doi.org/10.1212/WNL.0000000000001718.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Salter A, Tyry T, Wang G, Fox RJ, Cutter G, Marrie RA. Examining the joint effect of disability, health behaviors, and comorbidity on mortality in MS. Neurol Clin Pract. 2016;6:397–408.

    PubMed  PubMed Central  Google Scholar 

  82. Thormann A, Sørensen PS, Koch-Henriksen N, Laursen B, Magyari M. Comorbidity in multiple sclerosis is associated with diagnostic delays and increased mortality. Neurology. 2017;89:1668–75.

    PubMed  Google Scholar 

  83. Marrie RA, Yu BN, Leung S, Elliott L, Caetano P, Warren S, et al. Rising prevalence of vascular comorbidities in multiple sclerosis: validation of administrative definitions for diabetes, hypertension, and hyperlipidemia. Mult Scler J. 2012;18:1310–9.

    Google Scholar 

  84. Edwards NC, Munsell M, Menzin J, Phillips AL. Comorbidity in US patients with multiple sclerosis. Patient Relat Outcome Meas. 2018;9:97–102.

    PubMed  PubMed Central  Google Scholar 

  85. Anastasiou CA, Yannakoulia M, Kosmidis MH, et al. Mediterranean diet and cognitive health: initial results from the Hellenic Longitudinal Investigation of Ageing and Diet. PLoS ONE; 12. Epub ahead of print 1 August 2017. https://doi.org/10.1371/journal.pone.0182048.

  86. Valls-Pedret C, Sala-Vila A, Serra-Mir M, et al. Mediterranean diet and age-related cognitive decline: a randomized clinical trial. JAMA Intern Med. Epub ahead of print 11 May 2015. https://doi.org/10.1001/jamainternmed.2015.1668.

  87. Rees K, Takeda A, Martin N, Ellis L, Wijesekara D, Vepa A, Das A, Hartley L, Stranges S, Cochrane Heart Group Mediterranean-style diet for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev; 2019. Epub ahead of print 13 march 2019. https://doi.org/10.1002/14651858.CD009825.pub3.

  88. Wu L, Sun D. Adherence to Mediterranean diet and risk of developing cognitive disorders: an updated systematic review and meta-analysis of prospective cohort studies. Sci Rep; 7. Epub ahead of print 23 January 2017. https://doi.org/10.1038/srep41317.

  89. Mastronuzzi T, Grattagliano I. Nutrition as a health determinant in elderly patients. Curr Med Chem. 2019;26:3652–61.

    CAS  PubMed  Google Scholar 

  90. Motl RW, Pilutti LA. The benefits of exercise training in multiple sclerosis. Nat Rev Neurol. 2012;8:487–97.

    PubMed  Google Scholar 

  91. Motl RW, Sandroff BM, Kwakkel G, Dalgas U, Feinstein A, Heesen C, et al. Exercise in patients with multiple sclerosis. Lancet Neurol. 2017;16:848–56.

    PubMed  Google Scholar 

  92. Rietberg MB, Brooks D, Uitdehaag BM, et al. Exercise therapy for multiple sclerosis. Cochrane Database Syst Rev; 2005. Epub ahead of print 24 January 2005. https://doi.org/10.1002/14651858.CD003980.pub2.

  93. Ewanchuk BW, Gharagozloo M, Peelen E, Pilutti LA. Exploring the role of physical activity and exercise for managing vascular comorbidities in people with multiple sclerosis: a scoping review. Mult Scler Relat Disord. 2018;26:19–32.

    PubMed  Google Scholar 

  94. Amatya B, Khan F, Galea M. Rehabilitation for people with multiple sclerosis: an overview of Cochrane Reviews. Cochrane Database Syst Rev; 2019. Epub ahead of print 14 January 2019. https://doi.org/10.1002/14651858.CD012732.pub2.

  95. Müller L, Pawelec G. Aging and immunity – impact of behavioral intervention. Brain Behav Immun. 2014;39:8–22.

    PubMed  Google Scholar 

  96. Bollaert RE, Motl RW. Physical and cognitive functions, physical activity, and sedentary behavior in older adults with multiple sclerosis. J Geriatr Phys Ther. 2019;42:304–12.

    PubMed  Google Scholar 

  97. Ploughman M, Harris C, Wallack EM, Drodge O, Beaulieu S, Mayo N, et al. Predictors of exercise participation in ambulatory and non-ambulatory older people with multiple sclerosis. PeerJ. 2015;3:e1158.

    PubMed  PubMed Central  Google Scholar 

  98. Kalb R, Beier M, Benedict RH, et al. Recommendations for cognitive screening and management in multiple sclerosis care. Mult Scler J; 16.

  99. •• Villoslada P, Steinman L. New targets and therapeutics for neuroprotection, remyelination and repair in multiple sclerosis. Expert Opin Investig Drugs 2020; 29: 443–459. This is a detailed review of neuroprotective and remyelination therapeutic targets in MS.

  100. Scolding NJ, Pasquini M, Reingold SC, Cohen JA, International Conference on Cell-Based Therapies for Multiple Sclerosis, Atkins H, et al. Cell-based therapeutic strategies for multiple sclerosis. Brain. 2017;140:2776–96.

    PubMed  PubMed Central  Google Scholar 

  101. Muraro PA, Pasquini M, Atkins HL, Bowen JD, Farge D, Fassas A, et al. Long-term outcomes after autologous hematopoietic stem cell transplantation for multiple sclerosis. JAMA Neurol. 2017;74:459–69.

    PubMed  PubMed Central  Google Scholar 

  102. Uccelli A, Laroni A, Freedman MS. Mesenchymal stem cells as treatment for MS - progress to date. Mult Scler J. 2012;19:515–9.

    Google Scholar 

  103. • Neumann B, Segel M, Chalut KJ, et al. Remyelination and ageing: reversing the ravages of time. Mult Scler J 2019; 25: 1835–1841. This review discusses the impact of aging on remyelination and potential interventions for older patients.

  104. Rivera FJ, de la Fuente AG, Zhao C, Silva ME, Gonzalez GA, Wodnar R, et al. Aging restricts the ability of mesenchymal stem cells to promote the generation of oligodendrocytes during remyelination. Glia. 2019;67:1510–25.

    PubMed  PubMed Central  Google Scholar 

  105. Ruckh JM, Zhao J-W, Shadrach JL, van Wijngaarden P, Rao TN, Wagers AJ, et al. Rejuvenation of regeneration in the aging central nervous system. Cell Stem Cell. 2012;10:96–103.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Neumann B, Baror R, Zhao C, et al. Metformin restores CNS remyelination capacity by rejuvenating aged stem cells. Cell Stem Cell 2019; 25: 473–485.e8.

  107. Natrajan MS, de la Fuente AG, Crawford AH, Linehan E, Nuñez V, Johnson KR, et al. Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and remyelination. Brain. 2015;138:3581–97.

    PubMed  PubMed Central  Google Scholar 

  108. Barkhof F, Hulst HE, Drulovic J, Uitdehaag BMJ, Matsuda K, Landin R, et al. Ibudilast in relapsing-remitting multiple sclerosis: a neuroprotectant? Neurology. 2010;74:1033–40.

    CAS  PubMed  Google Scholar 

  109. Fox RJ, Coffey CS, Conwit R, Cudkowicz ME, Gleason T, Goodman A, et al. Phase 2 trial of ibudilast in progressive multiple sclerosis. N Engl J Med. 2018;379:846–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Demicheva E, Cui Y-F, Bardwell P, Barghorn S, Kron M, Meyer AH, et al. Targeting repulsive guidance molecule A to promote regeneration and neuroprotection in multiple sclerosis. Cell Rep. 2015;10:1887–98.

    CAS  PubMed  Google Scholar 

  111. Tanabe S, Fujita Y, Ikuma K, Yamashita T. Inhibiting repulsive guidance molecule-a suppresses secondary progression in mouse models of multiple sclerosis. Cell Death Dis. 2018;9:1061.

    PubMed  PubMed Central  Google Scholar 

  112. •• Oost W, Talma N, Meilof JF, et al. Targeting senescence to delay progression of multiple sclerosis. J Mol Med 2018; 96: 1153–1166. This is a detailed review of senescent changes that occur in immune and CNS cells and potential treatment strategies.

  113. Krysko KM, Henry RG, Cree BAC, Lin J, University of California, San Francisco MS‐EPIC Team, Caillier S, et al. Telomere length is associated with disability progression in multiple sclerosis. Ann Neurol. 2019;86:671–82.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Le H. Hua.

Ethics declarations

Conflict of Interest

LHH has received speaking and consulting fees from Biogen, Genzyme, Genentech, Novartis, Bristol Myers Squibb, and EMD Serono.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This Article is part of the Topical Collection on Multiple Sclerosis and Related Disorders

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hua, L.H. Treating MS After 50: the Role of Age in Therapeutic Decision-Making. Curr Treat Options Neurol 23, 8 (2021). https://doi.org/10.1007/s11940-021-00662-8

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11940-021-00662-8

Keywords

Navigation