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Brain MRI disease burden and sex differences in cognitive performance of patients with multiple sclerosis

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Abstract

Background

Although there is evidence that shows worse cognitive functioning in male patients with multiple sclerosis (MS), the role of brain pathology in this context is under-investigated.

Objective

To investigate sex differences in cognitive performance of MS patients, in the context of brain pathology and disease burden.

Methods

Brain MRI, neurological examination, neuropsychological assessment (Brief International Cognitive Assessment in MS—BICAMS, and Paced Auditory Verbal Learning Test—PASAT), and patient-reported outcome questionnaires were performed/administered in 1052 MS patients.

Results

Females had higher raw scores in the Symbol Digit Modalities Test (SDMT) (57.0 vs. 54.0; p < 0.001) and Categorical Verbal Learning Test (CVLT) (63.0 vs. 57.0; p < 0.001), but paradoxically, females evaluated their cognitive performance by MS Neuropsychological Questionnaire as being worse (16.6 vs 14.5, p = 0.004). Females had a trend for a weaker negative correlation between T2 lesion volume and SDMT (\(\rho\) = – 0.37 in females vs. – 0.46 in men; interaction p = 0.038). On the other hand, women had a trend for a stronger correlation between Brain Parenchymal Fraction (BPF) and a visual memory test (Spearman’s \(\rho\) = 0.31 vs. 0.21; interaction p = 0.016). All these trends were not significant after correction for false discovery rate.

Conclusions

Although, females consider their cognition as worse, males had at a group level slightly worse verbal memory and information processing speed. However, the sex differences in cognitive performance were smaller than the variability of scores within the same sex group. Brain MRI measures did not explain the sex differences in cognitive performance among MS patients.

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References

  1. Benedict RHB, Amato MP, DeLuca J, Geurts JJG (2020) Cognitive impairment in multiple sclerosis: clinical management, MRI, and therapeutic avenues. The Lancet Neurology 19(10):860–871. https://doi.org/10.1016/s1474-4422(20)30277-5

    Article  PubMed  PubMed Central  Google Scholar 

  2. Rao SM, Leo GJ, Bernardin L, Unverzagt F (1991) Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 41 (5):685–691. doi:https://doi.org/10.1212/wnl.41.5.685

  3. Rao SM (1990) A manual for the brief repeatable battery of neuropsychological tests in multiple sclerosis. National Multiple Sclerosis Society, New York

    Google Scholar 

  4. Benedict RHB, Cookfair D, Gavett R, Gunther M, Munschauer F, Garg N, Weinstock-Guttman B (2006) Validity of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS). J Int Neuropsycholog Soc. https://doi.org/10.1017/s1355617706060723

    Article  Google Scholar 

  5. Benedict RH, Amato MP, Boringa J, Brochet B, Foley F, Fredrikson S, Hamalainen P, Hartung H, Krupp L, Penner I, Reder AT, Langdon D (2012) Brief International Cognitive Assessment for MS (BICAMS): international standards for validation. BMC Neurol 12:55. https://doi.org/10.1186/1471-2377-12-55

    Article  PubMed  PubMed Central  Google Scholar 

  6. Langdon DW, Amato MP, Boringa J, Brochet B, Foley F, Fredrikson S, Hamalainen P, Hartung HP, Krupp L, Penner IK, Reder AT, Benedict RH (2012) Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Mult Scler 18(6):891–898. https://doi.org/10.1177/1352458511431076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Benedict RH, Zivadinov R (2011) Risk factors for and management of cognitive dysfunction in multiple sclerosis. Nat Rev Neurol 7(6):332–342. https://doi.org/10.1038/nrneurol.2011.61

    Article  PubMed  Google Scholar 

  8. Sumowski JF, Benedict R, Enzinger C, Filippi M, Geurts JJ, Hamalainen P, Hulst H, Inglese M, Leavitt VM, Rocca MA, Rosti-Otajarvi EM, Rao S (2018) Cognition in multiple sclerosis: state of the field and priorities for the future. Neurology 90(6):278–288. https://doi.org/10.1212/WNL.0000000000004977

    Article  PubMed  PubMed Central  Google Scholar 

  9. Jorm A, Anstey K, Christensen H, Rodgers B (2004) Gender differences in cognitive abilities: the mediating role of health state and health habits. Intelligence 32:7–23. https://doi.org/10.1016/j.intell.2003.08.001

    Article  Google Scholar 

  10. Roivainen E (2011) Gender differences in processing speed: a review of recent research. Learn Individ Differ 21:145–149. https://doi.org/10.1016/j.lindif.2010.11.021

    Article  Google Scholar 

  11. Lezak MD, Howieson DB, Bigler ED, Tranel D (2012) Neuropsychological assessment, 5th edn. Oxford University Press, New York

    Google Scholar 

  12. Strober LB, Bruce JM, Arnett PA, Alschuler KN, Lebkuecher A, Di Benedetto M, Cozart J, Thelen J, Guty E, Roman C (2020) A new look at an old test: Normative data of the symbol digit modalities test –Oral version. Multiple Sclerosis and Related Disorders 43:102154. https://doi.org/10.1016/j.msard.2020.102154

    Article  CAS  PubMed  Google Scholar 

  13. Goretti B, Niccolai C, Hakiki B, Sturchio A, Falautano M, Minacapelli E, Martinelli V, Incerti C, Nocentini U, Murgia M, Fenu G, Cocco E, Marrosu MG, Garofalo E, Ambra FI, Maddestra M, Consalvo M, Viterbo RG, Trojano M, Losignore NA, Zimatore GB, Pietrolongo E, Lugaresi A, Langdon D, Portaccio E, Amato MP (2014) The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS): normative values with gender, age and education corrections in the Italian population. BMC Neurol 14:171. https://doi.org/10.1186/s12883-014-0171-6

    Article  PubMed  PubMed Central  Google Scholar 

  14. Voskuhl RR, Patel K, Paul F, Gold SM, Scheel M, Kuchling J, Cooper G, Asseyer S, Chien C, Brandt AU, Meyer CE, Mackenzie-Graham A (2020) Sex differences in brain atrophy in multiple sclerosis. Biol Sex Differ. https://doi.org/10.1186/s13293-020-00326-3

    Article  PubMed  PubMed Central  Google Scholar 

  15. Voskuhl RR (2020) The effect of sex on multiple sclerosis risk and disease progression. Mult Scler J 26(5):554–560. https://doi.org/10.1177/1352458519892491

    Article  Google Scholar 

  16. Gilli F, DiSano KD, Pachner AR (2020) SeXX matters in multiple sclerosis. Front Neurol. https://doi.org/10.3389/fneur.2020.00616

    Article  PubMed  PubMed Central  Google Scholar 

  17. Koch M, Kingwell E, Rieckmann P, Tremlett H (2010) The natural history of secondary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 81(9):1039–1043. https://doi.org/10.1136/jnnp.2010.208173

    Article  PubMed  Google Scholar 

  18. Savettieri G, Messina D, Andreoli V, Bonavita S, Caltagirone C, Cittadella R, Farina D, Fazio MC, Girlanda P, Le Pira F, Liguori M, Lugaresi A, Nocentini U, Reggio A, Salemi G, Tedeschi G, Trojano M, Valentino P, Quattrone A (2004) Gender-related effect of clinical and genetic variables on the cognitive impairment in multiple sclerosis. J Neurol 251(10):1208–1214. https://doi.org/10.1007/s00415-004-0508-y

    Article  PubMed  Google Scholar 

  19. 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):787–793. https://doi.org/10.1177/1352458506070933

    Article  CAS  PubMed  Google Scholar 

  20. Beatty WW, Aupperle RL (2002) Sex differences in cognitive impairment in multiple sclerosis. Clin Neuropsychol 16(4):472–480. https://doi.org/10.1076/clin.16.4.472.13904

    Article  PubMed  Google Scholar 

  21. Schoonheim MM, Popescu V, Rueda Lopes FC, Wiebenga OT, Vrenken H, Douw L, Polman CH, Geurts JJG, Barkhof F (2012) Subcortical atrophy and cognition: sex effects in multiple sclerosis. Neurology 79(17):1754–1761. https://doi.org/10.1212/wnl.0b013e3182703f46

    Article  PubMed  Google Scholar 

  22. Schoonheim MM, Vigeveno RM, Lopes FCR, Pouwels PJW, Polman CH, Barkhof F, Geurts JJG (2014) Sex-specific extent and severity of white matter damage in multiple sclerosis: implications for cognitive decline. Hum Brain Mapp 35(5):2348–2358. https://doi.org/10.1002/hbm.22332

    Article  PubMed  Google Scholar 

  23. Uher T, Krasensky J, Vaneckova M, Sobisek L, Seidl Z, Havrdova E, Bergsland N, Dwyer MG, Horakova D, Zivadinov R (2017) A novel semiautomated pipeline to measure brain atrophy and lesion burden in multiple sclerosis: a long-term comparative study. J Neuroimaging 27(6):620–629. https://doi.org/10.1111/jon.12445

    Article  PubMed  Google Scholar 

  24. Uher T, Krasensky J, Sobisek L, Blahova Dusankova J, Seidl Z, Kubala Havrdova E, Sormani MP, Horakova D, Kalincik T, Vaneckova M (2018) Cognitive clinico-radiological paradox in early stages of multiple sclerosis. Ann Clin Transl Neurol 5(1):81–91. https://doi.org/10.1002/acn3.512

    Article  CAS  PubMed  Google Scholar 

  25. Uher T, Vaneckova M, Sormani MP, Krasensky J, Sobisek L, Dusankova JB, Seidl Z, Havrdova E, Kalincik T, Benedict RH, Horakova D (2017) Identification of multiple sclerosis patients at highest risk of cognitive impairment using an integrated brain magnetic resonance imaging assessment approach. Eur J Neurol 24(2):292–301. https://doi.org/10.1111/ene.13200

    Article  CAS  PubMed  Google Scholar 

  26. Dusankova JB, Kalincik T, Havrdova E, Benedict RH (2012) Cross cultural validation of the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) and the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Clin Neuropsychol 26(7):1186–1200. https://doi.org/10.1080/13854046.2012.725101

    Article  PubMed  Google Scholar 

  27. Smith A (1982) Symbol Digit Modalities Test (SDMT): Manual. Western Psychological Services, Los Angeles

    Google Scholar 

  28. Bezdíček O, Preiss M (2009) Kalifornský test verbálního učení – druhé vydání: Psychometrická analýza českého převodu. Československá psychologie LIII 6:573–586

    Google Scholar 

  29. Benedict R (1997) Brief visuospatial memory test—revised: professional manual. Psychological Assessment Resources Inc, Odessa

    Google Scholar 

  30. Beck AT, Steer RA, Carbin MG (1988) Psychometric properties of the Beck Depression Inventory: twenty-five years of evaluation. Clin Psychol Rev 8(1):77–100. https://doi.org/10.1016/0272-7358(88)90050-5

    Article  Google Scholar 

  31. Benedict RH, Munschauer F, Linn R, Miller C, Murphy E, Foley F, Jacobs L (2003) Screening for multiple sclerosis cognitive impairment using a self-administered 15-item questionnaire. Mult Scler J 9(1):95–101. https://doi.org/10.1191/1352458503ms861oa

    Article  CAS  Google Scholar 

  32. R Core Team (2022) R: A language and environment for statistical computing. 4.2.2. edn. R Foundation for Statistical Computing, Vienna, Austria

  33. IBM Corp. (2013) IBM SPSS Statistics for Windows. 22.0 edn. Armonk, NY

  34. Barro C, Benkert P, Disanto G, Tsagkas C, Amann M, Naegelin Y, Leppert D, Gobbi C, Granziera C, Yaldizli O, Michalak Z, Wuerfel J, Kappos L, Parmar K, Kuhle J (2018) Serum neurofilament as a predictor of disease worsening and brain and spinal cord atrophy in multiple sclerosis. Brain 141(8):2382–2391. https://doi.org/10.1093/brain/awy154

    Article  PubMed  Google Scholar 

  35. Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Lawrence Erlbaum Associates, New Jersey

    Google Scholar 

  36. Strober LB, Bruce JM, Arnett PA, Alschuler KN, Lebkuecher A, Di Benedetto M, Cozart J, Thelen J, Guty E, Roman C (2020) A new look at an old test: normative data of the symbol digit modalities test-oral version. Mult Scler Relat Disord 43:102154. https://doi.org/10.1016/j.msard.2020.102154

    Article  CAS  PubMed  Google Scholar 

  37. D’Hooghe MB, De Cock A, Van Remoortel A, Benedict RHB, Eelen P, Peeters E, D’Haeseleer M, De Keyser J, Nagels G (2020) Correlations of health status indicators with perceived neuropsychological impairment and cognitive processing speed in multiple sclerosis. Multiple Scler Related Disord 39:101904. https://doi.org/10.1016/j.msard.2019.101904

    Article  Google Scholar 

  38. O’Brien A, Gaudino-Goering E, Shawaryn M, Komaroff E, Moore NB, DeLuca J (2007) Relationship of the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) to functional, emotional, and neuropsychological outcomes. Arch Clin Neuropsychol 22(8):933–948. https://doi.org/10.1016/j.acn.2007.07.002

    Article  PubMed  Google Scholar 

  39. Kinsinger SW, Lattie E, Mohr DC (2010) Relationship between depression, fatigue, subjective cognitive impairment, and objective neuropsychological functioning in patients with multiple sclerosis. Neuropsychology 24(5):573–580. https://doi.org/10.1037/a0019222

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This work was supported by the institutional support of the hospital research [RVO VFN 64165], Czech Ministry of Education [project Cooperation LF1, research area Neuroscience], The project National Institute for Neurological Research—funded by the European Union—Next Generation EU [Programme EXCELES, ID project No LX22NPO5107], Czech Ministry of Health project [grant number NU22-04-00193], the Charles University Grant Agency (GAUK) [grant number 1154218].

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Author notes

  1. Jiri Motyl and Lucie Friedova have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Multiple Sclerosis Center, Charles University and General University Hospital, Katerinska 30, 120 00, Prague, Czech Republic

    Jiri Motyl, Lucie Friedova, Jana Blahova Dusankova, Eva Kubala Havrdova, Dana Horakova & Tomas Uher

  2. Department of Neurology, Buffalo Neuroimaging Analysis Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA

    Ranjani Ganapathy Subramanian & Tom A. Fuchs

  3. Department of Radiology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic

    Manuela Vaneckova & Jan Krasensky

  4. Department of Physiotherapy, Faculty of Health Care, University of Presov, Prešov, Slovak Republic

    Tomas Uher

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Correspondence to Tomas Uher.

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Conflict of Interest

J.M. received compensation for travel, conference fees, and speaker honoraria from Sanofi Genzyme, Biogen, Novartis, and Merck. L.F. received compensation for travel, conference fees, and speaker honoraria from Biogen and Roche. RG, TF and JBD have nothing to declare. MV received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck Serono, and Teva, as well as support for research activities from Biogen Idec. JK received financial support for research activities from Biogen Idec. EKH received speaker honoraria and consultant fees from Biogen Idec, Merck Serono, Novartis, Genzyme, Teva, Actelion, and Receptos, as well as support for research activities from Biogen Idec and Merck Serono. DH received compensation for travel, speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck Serono, Bayer Shering, and Teva, as well as support for research activities from Biogen Idec. TU received financial support for conference travel and honoraria from Biogen Idec, Novartis, Roche, Genzyme, and Merck Serono, as well as support for research activities from Biogen Idec and Sanofi.

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Motyl, J., Friedova, L., Ganapathy Subramanian, R. et al. Brain MRI disease burden and sex differences in cognitive performance of patients with multiple sclerosis. Acta Neurol Belg 124, 109–118 (2024). https://doi.org/10.1007/s13760-023-02350-7

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