Research Article| Volume 73, 104626, May 2023

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The impact of cognitive impairment on disease burden in Chinese patients with multiple sclerosis: A model simulation study


      • The prevalence of cognitive impairment (CI) in Chinese patients with MS is above 40% at the stage of relapsing-remitting multiple sclerosis (RRMS) and could further increase to over 80% after the progression to secondary-progressive multiple sclerosis (SPMS).
      • Based on the simulations for both disease progression and development of CI in Chinese with newly diagnosed RRMS, over 85% of RRMS patients could develop to CI over their lifetime.
      • The developed CI could make the major contribution to the disease burden of RRMS by substantially increasing mortality, impairing quality of life, and increasing both direct medical costs and indirect costs.
      • The projected heavy disease burden associated with CI in Chinese RRMS patients suggests that routine cognitive function assessment and CI management should be implemented in the management of RRMS.



      Cognitive impairment (CI) is prevalent in Chinese patients with relapsing-remitting multiple sclerosis (RRMS).


      A decision analytic model was constructed to simulate Chinese patients with newly diagnosed RRMS and their matched control cohort without MS for the risks of developing CI, developing secondary progressive MS (SPMS), and mortality. Both English and Chinese bibliographic databases were searched for evidence to estimate model inputs. Base case analysis and sensitivity analysis were conducted for the point estimations and uncertainty of the measured burden outcomes.


      Model simulations estimated that the lifetime cumulative risk of CI in newly diagnosed RRMS patients was 85.2%. Relative to the matched control cohort, newly diagnosed RRMS patients were associated with a lower life expectancy (33.2 years vs. 41.7 years, difference: -8.5 years), lower quality-adjusted life years (QALY) (18.4 QALY vs. 38.4 QALY, difference: -19.9 QALY), and higher lifetime medical costs (¥613,883 vs. ¥202,726, difference: ¥411,157) and indirect costs (¥1,099,021 vs. ¥94,612, difference: ¥1,004,410). Patients who developed CI accounted for at least half of the measured burden. The disease burden outcomes were mainly driven by the risk of developing CI, progression risk from RRMS to SPMS, hazard ratios of mortality associated with CI relative to no CI, utility of patients with RRMS, annual relapse risk, and annual costs of personal care.


      Most Chinese patients with newly diagnosed RRMS are likely to develop CI in their lifetime, and such patients that develop CI could significantly contribute to the disease burden of RRMS.


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        • Achiron A.
        • Barak Y.
        Cognitive impairment in probable multiple sclerosis.
        J. Neurol. Neurosurg. Psychiatry. 2003; 74: 443-446
        • Ahmad H.
        • Van Der Mei I.
        • Taylor B.V.
        • Lucas R.M.
        • Ponsonby A.L.
        • Lechner-Scott J.
        • Dear K.
        • Valery P.
        • Clarke P.M.
        • Simpson S.
        Estimation of annual probabilities of changing disability levels in Australians with relapsing-remitting multiple sclerosis.
        Mult. Scler. 2019; 25: 1800-1808
        • Benedict R.H.
        • Amato M.P.
        • DeLuca J.
        • Geurts J.J.
        Cognitive impairment in multiple sclerosis: clinical management, MRI, and therapeutic avenues.
        Lancet Neurol. 2020; 19: 860-871
        • Benito-León J.
        • Manuel Morales J.
        • Rivera-Navarro J.
        • Mitchell A.J.
        A review about the impact of multiple sclerosis on health-related quality of life.
        Disabil. Rehabil. 2003; 25: 1291-1303
        • Blinkenberg M.
        • Kjellberg J.
        • Ibsen R.
        • Magyari M.
        Increased socioeconomic burden in patients with primary progressive multiple sclerosis: a Danish nationwide population-based study.
        Mult. Scler. Relat. Disord. 2020; 46102567
        • Bøe Lunde H.M.
        • Telstad W.
        • Grytten N.
        • Kyte L.
        • Aarseth J.
        • Myhr K.M.
        • Bø L.
        Employment among patients with multiple sclerosis-a population study.
        PLOS One. 2014; 9e103317
        • Borghi M.
        • Cavallo M.
        • Carletto S.
        • Ostacoli L.
        • Zuffranieri M.
        • Picci R.L.
        • Scavelli F.
        • Johnston H.
        • Furlan P.M.
        • Bertolotto A.
        Presence and significant determinants of cognitive impairment in a large sample of patients with multiple sclerosis.
        PLOS One. 2013; 8: e69820
        • Caceres F.
        • Vanotti S.
        • Benedict R.
        • Group R.W.
        Cognitive and neuropsychiatric disorders among multiple sclerosis patients from Latin America: results of the RELACCEM study.
        Mult. Scler. Relat. Disord. 2014; 3: 335-340
        • 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: 143-147
        • Cavaco S.
        • Ferreira I.
        • Moreira I.
        • Santos E.
        • Samões R.
        • Sousa A.P.
        • Pinheiro J.
        • Teixeira-Pinto A.
        • Martins da Silva A.
        Cognitive dysfunction and mortality in multiple sclerosis: long-term retrospective review.
        Mult. Scler. 2022; 28: 1382-1391
        • Crielaard L.
        • Kavaliunas A.
        • Ramanujam R.
        • Olsson T.
        • Hillert J.
        • Stridh P.
        • Kockum I.
        • Manouchehrinia A.
        Factors associated with and long-term outcome of benign multiple sclerosis: a nationwide cohort study.
        J. Neurol. Neurosurg. Psychiatry. 2019; 90: 761-767
        • Dobson R.
        • Giovannoni G.
        Multiple sclerosis–a review.
        Eur. J. Neurol. 2019; 26: 27-40
        • Dong X.
        • Xu G.
        • Wang J.
        • Yin N.
        • Meng N.
        Clinical and MRI predictors of cognitive decline in patients with relapsing-remitting multiple sclerosis: a 2-year longitudinal study.
        Mult. Scler. Relat. Disord. 2022; 65103838
        • Du Y.
        • Min R.
        • Zhang X.
        • Fang P.
        Factors associated with the healthcare expenditures of patients with multiple sclerosis in urban areas of China estimated by a generalized estimating equation.
        Expert Rev. Pharmacoecon. Outcomes Res. 2021; 21: 137-144
        • Eijlers A.J.
        • van Geest Q.
        • Dekker I.
        • Steenwijk M.D.
        • Meijer K.A.
        • Hulst H.E.
        • Barkhof F.
        • Uitdehaag B.M.
        • Schoonheim M.M.
        • Geurts J.J.
        Predicting cognitive decline in multiple sclerosis: a 5-year follow-up study.
        Brain. 2018; 141: 2605-2618
        • Gil-González I.
        • Martín-Rodríguez A.
        • Conrad R.
        • Pérez-San-Gregorio M.Á.
        Quality of life in adults with multiple sclerosis: a systematic review.
        BMJ Open. 2020; 10e041249
        • Gross H.J.
        • Watson C.
        Characteristics, burden of illness, and physical functioning of patients with relapsing-remitting and secondary progressive multiple sclerosis: a cross-sectional US survey.
        Neuropsychiatr. Dis. Treat. 2017; 13: 1349-1357
        • Hader W.J.
        Disability and survival of multiple sclerosis in Saskatoon, Saskatchewan.
        Can. J. Neurol. Sci. 2010; 37: 28-35
        • Hategeka C.
        • Traboulsee A.L.
        • McMullen K.
        • Lynd L.D.
        Association of unemployment and informal care with stigma in multiple sclerosis: evidence from the survey on living with neurological conditions in Canada.
        Int. J. MS Care. 2019; 21: 214-225
        • Henriksson F.
        • Jönsson B.
        The economic cost of multiple sclerosis in Sweden in 1994.
        Pharmacoeconomics. 1998; 13: 597-606
        • Hojjat S.P.
        • Cantrell C.G.
        • Vitorino R.
        • Feinstein A.
        • Shirzadi Z.
        • MacIntosh B.J.
        • Crane D.E.
        • Zhang L.
        • Morrow S.A.
        • Lee L.
        Regional reduction in cortical blood flow among cognitively impaired adults with relapsing-remitting multiple sclerosis patients.
        Mult. Scler. 2016; 22: 1421-1428
        • Hsu C.Y.
        • Ro L.S.
        • Chen L.J.
        • Chang C.W.
        • Chang K.H.
        • Wu I.H.
        • Lin A.
        • Hsiao F.Y.
        Epidemiology, treatment patterns and healthcare utilizations in multiple sclerosis in Taiwan.
        Sci. Rep. 2021; 11: 7727
        • Huijbregts S.
        • Kalkers N.
        • De Sonneville L.
        • De Groot V.
        • Reuling I.
        • Polman C.
        Differences in cognitive impairment of relapsing remitting, secondary, and primary progressive MS.
        Neurology. 2004; 63: 335-339
        • Inojosa H.
        • Proschmann U.
        • Akgün K.
        • Ziemssen T.
        A focus on secondary progressive multiple sclerosis (SPMS): challenges in diagnosis and definition.
        J. Neurol. 2021; 268: 1210-1221
        • Jia J.
        • Wei C.
        • Chen S.
        • Li F.
        • Tang Y.
        • Qin W.
        • Zhao L.
        • Jin H.
        • Xu H.
        • Wang F.
        The cost of Alzheimer's disease in China and re-estimation of costs worldwide.
        Alzheimers Dement. 2018; 14: 483-491
        • Jones K.H.
        • Ford D.V.
        • Jones P.A.
        • John A.
        • Middleton R.M.
        • Lockhart-Jones H.
        • Peng J.
        • Osborne L.A.
        • Noble J.G.
        How people with multiple sclerosis rate their quality of life: an EQ-5D survey via the UK MS register.
        PLOS One. 2013; 8: e65640
        • Kappos L.
        • Bar-Or A.
        • Cree B.A.
        • Fox R.J.
        • Giovannoni G.
        • Gold R.
        • Vermersch P.
        • Arnold D.L.
        • Arnould S.
        • Scherz T.
        Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study.
        Lancet. 2018; 391: 1263-1273
        • Kavaliunas A.
        • Tinghög P.
        • Friberg E.
        • Olsson T.
        • Alexanderson K.
        • Hillert J.
        • Karrenbauer V.D.
        Cognitive function predicts work disability among multiple sclerosis patients.
        Mult. Scler. J. Exp. Transl. Clin. 2019; 52055217318822134
        • Kingwell E.
        • Van der Kop M.
        • Zhao Y.
        • Shirani A.
        • Zhu F.
        • Oger J.
        • Tremlett H.
        Relative mortality and survival in multiple sclerosis: findings from British Columbia.
        Canada. J. Neurol. Neurosurg. Psychiatry. 2012; 83: 61-66
        • Leray E.
        • Moreau T.
        • Fromont A.
        • Edan G.
        Epidemiology of multiple sclerosis.
        Rev. Neurol. (Paris). 2016; 172: 3-13
        • Lunde H.M.B.
        • Assmus J.
        • Myhr K.-.M.
        • Bø L.
        • Grytten N.
        Survival and cause of death in multiple sclerosis: a 60-year longitudinal population study.
        J. Neurol. Neurosurg. Psychiatry. 2017; 88: 621-625
        • Maltby V.E.
        • Lea R.A.
        • Reeves P.
        • Saugbjerg B.
        • Lechner-Scott J.
        Reduced cognitive function contributes to economic burden of multiple sclerosis.
        Mult. Scler. Relat. Disord. 2022; 60103707
        • Müller S.
        • Heidler T.
        • Fuchs A.
        • Pfaff A.
        • Ernst K.
        • Ladinek G.
        • Wilke T.
        Real-world treatment of patients with multiple sclerosis per MS subtype and associated healthcare resource use: an analysis based on 13,333 patients in Germany.
        Neurol. Ther. 2020; 9: 67-83
        • Ng A.
        • Wong A.
        • Au C.
        • Mok V.
        • Lau A.
        Cognitive performance and clinical profiles of relapsing and progressive multiple sclerosis patients in Hong Kong.
        Mult. Scler. 2020; 26: NP51
        • Nohara C.
        • Hase M.
        • Liebert R.
        • Wu N.
        The burden of multiple sclerosis in Japan.
        J. Med. Econ. 2017; 20: 1290-1298
        • Ozakbas S.
        • Turkoglu R.
        • Tamam Y.
        • Terzi M.
        • Taskapilioglu O.
        • Yucesan C.
        • Baser H.L.
        • Gencer M.
        • Akil E.
        • Sen S.
        Prevalence of and risk factors for cognitive impairment in patients with relapsing-remitting multiple sclerosis: multi-center, controlled trial.
        Mult. Scler. Relat. Disord. 2018; 22: 70-76
        • Palmer A.J.
        • van der Mei I.
        • Taylor B.V.
        • Clarke P.M.
        • Simpson Jr, S.
        • Ahmad H.
        Modelling the impact of multiple sclerosis on life expectancy, quality-adjusted life years and total lifetime costs: evidence from Australia.
        Mult. Scler. 2020; 26: 411-420
        • Patti F.
        • Russo P.
        • Pappalardo A.
        • Macchia F.
        • Civalleri L.
        • Paolillo A.
        • Group F.S.
        Predictors of quality of life among patients with multiple sclerosis: an Italian cross-sectional study.
        J. Neurol. Sci. 2007; 252: 121-129
        • Rabadi M.H.
        • Aston C.E.
        Predictors of mortality in veterans with multiple sclerosis in an outpatient clinic setting.
        Int. J. MS Care. 2017; 19: 265-273
        • Ruano L.
        • Portaccio E.
        • Goretti B.
        • Niccolai C.
        • Severo M.
        • Patti F.
        • Cilia S.
        • Gallo P.
        • Grossi P.
        • Ghezzi A.
        Age and disability drive cognitive impairment in multiple sclerosis across disease subtypes.
        Mult. Scler. 2017; 23: 1258-1267
        • Sandi D.
        • Zsiros V.
        • Füvesi J.
        • Kincses Z.T.
        • Fricska-Nagy Z.
        • Lencsés G.
        • Vécsei L.
        • Bencsik K.
        Mortality in Hungarian patients with multiple sclerosis between 1993 and 2013.
        J. Neurol. Sci. 2016; 367: 329-332
      1. Statistical Communiqué of the People's Republic of China on the 2020. National Economic and Social Development. China National Bureau of Statistics, 2021, (Accessed April 5 2022).

        • Summers M.
        • Fisniku L.
        • Anderson V.
        • Miller D.
        • Cipolotti L.
        • Ron M.
        Cognitive impairment in relapsing–remitting multiple sclerosis can be predicted by imaging performed several years earlier.
        Mult. Scler. 2008; 14: 197-204
        • Tian D.C.
        • Zhang C.
        • Yuan M.
        • Yang X.
        • Gu H.
        • Li Z.
        • Wang Y.
        • Shi F.D.
        Incidence of multiple sclerosis in China: a nationwide hospital-based study.
        Lancet Reg. Health. West. Pac. 2020; 1100010
        • Torgauten H.M.
        • Myhr K.M.
        • Wergeland S.
        • Bø L.
        • Aarseth J.H.
        • Torkildsen Ø.
        Safety and efficacy of rituximab as first-and second line treatment in multiple sclerosis–a cohort study.
        Mult. Scler. J. Exp. Transl. Clin. 2021; 72055217320973049
        • Van Eijndhoven E.
        • Brauer M.
        • Kee R.
        • MacEwan J.
        • Mucha L.
        • Wong S.L.
        • Durand A.
        • Shafrin J.
        Modeling the impact of patient treatment preference on health outcomes in relapsing-remitting multiple sclerosis.
        J. Med. Econ. 2020; 23: 474-483
        • Vollmer T.
        • Huynh L.
        • Kelley C.
        • Galebach P.
        • Signorovitch J.
        • DiBernardo A.
        • Sasane R.
        Relationship between brain volume loss and cognitive outcomes among patients with multiple sclerosis: a systematic literature review.
        Neurol. Sci. 2016; 37: 165-179
        • Wang G.
        • Cheng Q.
        • Zheng R.
        • Tan Y.Y.
        • Sun X.K.
        • Zhou H.Y.
        • Ye X.L.
        • Wang Y.
        • Wang Z.
        • Sun B.M.
        Economic burden of Parkinson's disease in a developing country: a retrospective cost analysis in Shanghai, China.
        Mov. Disord. 2006; 21: 1439-1443
        • Yamabe K.
        • DiBonaventura M.D.
        • Pashos C.L.
        Health-related outcomes, health care resource utilization, and costs of multiple sclerosis in Japan compared with US and five EU countries.
        ClinicoEcon. Outcomes Res. 2019; 11: 61
        • Yang Y.
        Hospitalization expenses attributable to cognitive-frailty in the elderly in China: health services research: cost of care and implications for intervention.
        Alzheimers Dement. 2020; 16e039403
        • Zhang Y.
        • Xu Y.
        • Xu T.
        • Yin H.
        • Zhu Y.
        • Peng B.
        • Cui L.
        Prediction of long-term disability in Chinese patients with multiple sclerosis: a prospective cohort study.
        Mult. Scler. Relat. Disord. 2020; 46102461
        • Zhao L.
        • Ng A.
        • Chen Q.
        • Lam B.
        • Abrigo J.
        • Au C.
        • Mok V.C.
        • Wong A.
        • Lau A.Y.
        Impaired cognition is related to microstructural integrity in relapsing remitting multiple sclerosis.
        Ann. Clin. Transl. Neurol. 2020; 7: 1193-1203
        • Zhou R.
        • Zeng Q.
        • Yang H.
        • Xu Y.
        • Tan G.
        • Liu H.
        • Wang L.
        • Zhou H.
        • Zhang M.
        • Feng J.
        Status of immunotherapy acceptance in Chinese patients with multiple sclerosis: analysis of multiple sclerosis patient survival report 2018.
        Front. Neurol. 2021; 12651511