Neurological Sciences

, Volume 40, Issue 8, pp 1651–1657 | Cite as

Aging with multiple sclerosis: prevalence and profile of cognitive impairment

  • Mariana Branco
  • Luis Ruano
  • Emilio Portaccio
  • Benedetta Goretti
  • Claudia Niccolai
  • Francesco Patti
  • Clara Chisari
  • Paolo Gallo
  • Paola Grossi
  • Angelo Ghezzi
  • Marco Roscio
  • Flavia Mattioli
  • Fabio Bellomi
  • Marta Simone
  • Rosa Gemma Viterbo
  • Maria Pia AmatoEmail author
Original Article



The increase in life expectancy of patients with multiple sclerosis (MS) requires a better knowledge of disease features in the older patients group.


To describe the prevalence and profile of cognitive impairment (CI) in older patients with MS and perform a comparison with younger patients.


Patients were consecutively recruited for 6 months. Cognitive performance was assessed through the Brief Repeatable Battery and the Stroop Test. CI was defined as impairment in ≥ 2 cognitive domains.


We identified 111 patients older than 55 years (mean age 59.7 years). The prevalence of CI was 77.4%, which was significantly higher than in younger patients (42.8%; p < 0.01). Information processing speed was the most impaired domain (68.8%), followed by verbal learning (49.5%), executive function (47.7%), and visuospatial learning (26.6%). We found no significant differences in the prevalence of impairment in the distinct cognitive domains between older and younger patients with CI. Depression and fatigue were not associated with increased CI among patients in the older age group (p > 0.70).


There is a remarkably high frequency of CI in older patients with MS. The similar profile of CI between older and younger patients suggests that CI is mostly directly related to MS itself and not to comorbid age-related disorders.


Multiple sclerosis Cognitive impairment Aging Epidemiology 



This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

All the enrolled patients provided informed consent and the study was approved by the ethical committees of all recruiting institutions.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict of interest

The authors declare that there is no conflict of interest.


  1. 1.
    Marrie RA, Elliott L, Marriott J, Cossoy M, Blanchard J, Leung S, Yu N (2015) Effect of comorbidity on mortality in multiple sclerosis. Neurology 85(3):240–247. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Marrie RA, Yu N, Blanchard J, Leung S, Elliott L (2010) The rising prevalence and changing age distribution of multiple sclerosis in Manitoba. Neurology 74(6):465–471. CrossRefPubMedGoogle Scholar
  3. 3.
    Chiaravalloti ND, DeLuca J (2008) Cognitive impairment in multiple sclerosis. Lancet Neurol 7(12):1139–1151. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Amato MP, Zipoli V, Portaccio E (2006) Multiple sclerosis-related cognitive changes: a review of cross-sectional and longitudinal studies. J Neurol Sci 245(1–2):41–46. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    DeLuca J, Chelune GJ, Tulsky DS, Lengenfelder J, Chiaravalloti ND (2004) Is speed of processing or working memory the primary information processing deficit in multiple sclerosis? J Clin Exp Neuropsychol 26(4):550–562. CrossRefPubMedGoogle Scholar
  6. 6.
    Klewer J, Pohlau D, Nippert I, Haas J, Kugler J (2001) Problems reported by elderly patients with multiple sclerosis. J Neurosci Nurs 33(3):167–171CrossRefGoogle Scholar
  7. 7.
    Wood B, van der Mei IA, Ponsonby AL, Pittas F, Quinn S, Dwyer T, Lucas RM, Taylor BV (2013) Prevalence and concurrence of anxiety, depression and fatigue over time in multiple sclerosis. Mult Scler 19(2):217–224. CrossRefPubMedGoogle Scholar
  8. 8.
    Nunnari D, De Cola MC, D'Aleo G, Rifici C, Russo M, Sessa E, Bramanti P, Marino S (2015) Impact of depression, fatigue, and global measure of cortical volume on cognitive impairment in multiple sclerosis. Biomed Res Int 2015:519785. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Diamond BJ, Johnson SK, Kaufman M, Graves L (2008) Relationships between information processing, depression, fatigue and cognition in multiple sclerosis. Arch Clin Neuropsychol 23(2):189–199. CrossRefPubMedGoogle Scholar
  10. 10.
    Roy S, Frndak S, Drake AS, Irwin L, Zivadinov R, Weinstock-Guttman B, Benedict RH (2017) Differential effects of aging on motor and cognitive functioning in multiple sclerosis. Mult Scler 23(10):1385–1393. CrossRefPubMedGoogle Scholar
  11. 11.
    Ruano L, Portaccio E, Goretti B, Niccolai C, Severo M, Patti F, Cilia S, Gallo P, Grossi P, Ghezzi A, Roscio M, Mattioli F, Stampatori C, Trojano M, Viterbo RG, Amato MP (2017) Age and disability drive cognitive impairment in multiple sclerosis across disease subtypes. Mult Scler 23(9):1258–1267. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Muller S, Saur R, Greve B, Melms A, Hautzinger M, Fallgatter AJ, Leyhe T (2013) Recognition performance differentiates between elderly patients in the long term course of secondary progressive multiple sclerosis and amnestic mild cognitive impairment. Mult Scler 19(6):799–805. CrossRefPubMedGoogle Scholar
  13. 13.
    Roy S, Drake A, Snyder S, Cline B, Khan A, Fuchs T, Zivadinov R, Weinstock-Guttman B, Szigeti K, Benedict RHB (2018) Preliminary investigation of cognitive function in aged multiple sclerosis patients: challenges in detecting comorbid Alzheimer’s disease. Mult Scler Relat Disord 22:52–56. CrossRefPubMedGoogle Scholar
  14. 14.
    Bever CT Jr, Grattan L, Panitch HS, Johnson KP (1995) The brief repeatable battery of neuropsychological tests for multiple sclerosis: a preliminary serial study. Mult Scler 1(3):165–169CrossRefGoogle Scholar
  15. 15.
    Stroop JR (1935) Studies of interference in serial verbal reactions. J Exp Psychol 18(6):643–662. CrossRefGoogle Scholar
  16. 16.
    Amato MP, Portaccio E, Goretti B, Zipoli V, Ricchiuti L, De Caro MF, Patti F, Vecchio R, Sorbi S, Trojano M (2006) The Rao’s brief repeatable battery and Stroop test: normative values with age, education and gender corrections in an Italian population. Mult Scler 12(6):787–793CrossRefGoogle Scholar
  17. 17.
    Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD (1989) The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol 46(10):1121–1123CrossRefGoogle Scholar
  18. 18.
    Montgomery SA, Asberg M (1979) A new depression scale designed to be sensitive to change. Br J Psychiatry 134(4):382–389CrossRefGoogle Scholar
  19. 19.
    Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP (2013) The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement 9(1):63–75 e62. CrossRefPubMedGoogle Scholar
  20. 20.
    Sachdev PS, Lipnicki DM, Kochan NA, Crawford JD, Thalamuthu A, Andrews G, Brayne C, Matthews FE, Stephan BC, Lipton RB, Katz MJ, Ritchie K, Carriere I, Ancelin ML, Lam LC, Wong CH, Fung AW, Guaita A, Vaccaro R, Davin A, Ganguli M, Dodge H, Hughes T, Anstey KJ, Cherbuin N, Butterworth P, Ng TP, Gao Q, Reppermund S, Brodaty H, Schupf N, Manly J, Stern Y, Lobo A, Lopez-Anton R, Santabarbara J, Cohort Studies of Memory in an International C (2015) The prevalence of mild cognitive impairment in diverse geographical and ethnocultural regions: the COSMIC collaboration. PLoS One 10(11):e0142388. CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Polliack ML, Barak Y, Achiron A (2001) Late-onset multiple sclerosis. J Am Geriatr Soc 49(2):168–171CrossRefGoogle Scholar
  22. 22.
    Patti F, Nicoletti A, Messina S, Bruno E, Fermo SL, Quattrocchi G, Chisari CG, Maimone D, Cilia S, Zappia M (2015) Prevalence and incidence of cognitive impairment in multiple sclerosis: a population-based survey in Catania, Sicily. J Neurol 262(4):923–930. CrossRefPubMedGoogle Scholar
  23. 23.
    Amato MP, Razzolini L, Goretti B, Stromillo ML, Rossi F, Giorgio A, Hakiki B, Giannini M, Pasto L, Portaccio E, De Stefano N (2013) Cognitive reserve and cortical atrophy in multiple sclerosis: a longitudinal study. Neurology 80(19):1728–1733. CrossRefPubMedGoogle Scholar
  24. 24.
    Jonsson A, Andresen J, Storr L, Tscherning T, Soelberg Sorensen P, Ravnborg M (2006) Cognitive impairment in newly diagnosed multiple sclerosis patients: a 4-year follow-up study. J Neurol Sci 245(1–2):77–85. CrossRefPubMedGoogle Scholar
  25. 25.
    Gainotti G, Marra C, Villa G, Parlato V, Chiarotti F (1998) Sensitivity and specificity of some neuropsychological markers of Alzheimer dementia. Alzheimer Dis Assoc Disord 12(3):152–162CrossRefGoogle Scholar
  26. 26.
    Roman GC (2002) Vascular dementia may be the most common form of dementia in the elderly. J Neurol Sci 203-204:7–10CrossRefGoogle Scholar
  27. 27.
    Iadecola C (2013) The pathobiology of vascular dementia. Neuron 80(4):844–866. CrossRefPubMedGoogle Scholar
  28. 28.
    Schmidt R, Enzinger C, Ropele S, Schmidt H, Fazekas F (2006) Subcortical vascular cognitive impairment: similarities and differences with multiple sclerosis. J Neurol Sci 245(1–2):3–7. CrossRefPubMedGoogle Scholar
  29. 29.
    Prins ND, van Dijk EJ, den Heijer T, Vermeer SE, Jolles J, Koudstaal PJ, Hofman A, Breteler MM (2005) Cerebral small-vessel disease and decline in information processing speed, executive function and memory. Brain 128 (Pt 9:2034–2041. CrossRefPubMedGoogle Scholar
  30. 30.
    Marrie RA, Fisk J, Tremlett H, Wolfson C, Warren S, Blanchard J, Patten SB, Epidemiology CTit, Impact of Comorbidity on Multiple S (2016) Differing trends in the incidence of vascular comorbidity in MS and the general population. Neurol Clin Pract 6(2):120–128. CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Ruano L, Branco M, Portaccio E, Goretti B, Niccolai C, Patti F, Chisari C, Gallo P, Grossi P, Ghezzi A, Roscio M, Mattioli F, Stampatori C, Simone M, Viterbo RG, Amato MP (2018) Patients with paediatric-onset multiple sclerosis are at higher risk of cognitive impairment in adulthood: an Italian collaborative study. Mult Scler J 24(9):1234–1242. CrossRefGoogle Scholar
  32. 32.
    Smestad C, Sandvik L, Landro NI, Celius EG (2010) Cognitive impairment after three decades of multiple sclerosis. Eur J Neurol 17(3):499–505. CrossRefPubMedGoogle Scholar
  33. 33.
    Amato MP, Langdon D, Montalban X, Benedict RH, DeLuca J, Krupp LB, Thompson AJ, Comi G (2013) Treatment of cognitive impairment in multiple sclerosis: position paper. J Neurol 260(6):1452–1468. CrossRefPubMedGoogle Scholar
  34. 34.
    Riepl E, Pfeuffer S, Ruck T, Lohmann H, Wiendl H, Meuth SG, Johnen A (2017) Alemtuzumab improves cognitive processing speed in active multiple sclerosis-a longitudinal observational study. Front Neurol 8:730. CrossRefPubMedGoogle Scholar
  35. 35.
    Iaffaldano P, Viterbo RG, Paolicelli D, Lucchese G, Portaccio E, Goretti B, Direnzo V, D'Onghia M, Zoccolella S, Amato MP, Trojano M (2012) Impact of natalizumab on cognitive performances and fatigue in relapsing multiple sclerosis: a prospective, open-label, two years observational study. PLoS One 7(4):e35843. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Fondazione Società Italiana di Neurologia 2019

Authors and Affiliations

  • Mariana Branco
    • 1
    • 2
  • Luis Ruano
    • 1
    • 2
    • 3
  • Emilio Portaccio
    • 4
  • Benedetta Goretti
    • 4
    • 5
  • Claudia Niccolai
    • 5
  • Francesco Patti
    • 6
  • Clara Chisari
    • 6
  • Paolo Gallo
    • 7
  • Paola Grossi
    • 7
    • 8
  • Angelo Ghezzi
    • 9
  • Marco Roscio
    • 9
  • Flavia Mattioli
    • 10
  • Fabio Bellomi
    • 10
  • Marta Simone
    • 11
  • Rosa Gemma Viterbo
    • 12
  • Maria Pia Amato
    • 5
    • 13
    Email author
  1. 1.Neurology DepartmentCentro Hospitalar de Entre Douro e VougaSanta Maria da FeiraPortugal
  2. 2.Departamento de Epidemiologia Clínica Medicina Preditiva e Saúde PúblicaFaculdade de Medicina da Universidade do PortoPortoPortugal
  3. 3.EPIUnit, Instituto de Saúde PúblicaUniversidade do PortoPortoPortugal
  4. 4.SOC Neurologia - Firenze, AUSL Toscana CentroFlorenceItaly
  5. 5.Department NEUROFARBA, Section NeurosciencesUniversity of FlorenceFlorenceItaly
  6. 6.University of CataniaCataniaItaly
  7. 7.University of PadovaPadovaItaly
  8. 8.Department, ASST CremaNeuroimmunology Center, CardiocerebrovascularCremaItaly
  9. 9.Gallarate HospitalVareseItaly
  10. 10.ASST Spedali Civili Brescia Neuropsychology UnitBresciaItaly
  11. 11.Department of Basic Medical Sciences, Child and Adolescence Neuropsychiatry Unit, Neuroscience and Sense OrgansUniversity “Aldo Moro” BariBariItaly
  12. 12.University of BariBariItaly
  13. 13.IRCCS Fondazione Don Carlo GnocchiFlorenceItaly

Personalised recommendations