{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:55:56Z","timestamp":1790934956419,"version":"4.1.0"},"reference-count":24,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background: Multiple sclerosis (MS) is characterized by heterogeneous trajectories of motor and cognitive disability. This study aimed to characterize longitudinal cognitive and motor trajectories across MS phenotypes and to identify baseline predictors of subsequent worsening. Methods: This retrospective cohort included 68 adults with MS followed for approximately six years. Cognitive performance was assessed at baseline (T0) and follow-up (T1) using the Rao\u2019s Brief Repeatable Battery (BRB-N) and quantified using the Cognitive Impairment Index (CII). Clinical, demographic, neuropsychological, psychological, and neuroimaging variables were collected. Longitudinal cognitive changes were evaluated using linear mixed-effects models including baseline phenotype, time, and phenotype-by-time interaction. Logistic regression was used to investigate predictors of motor and cognitive worsening. Results: At baseline, 52.9% of patients met criteria for cognitive impairment. During follow-up, 50.0% experienced motor worsening and 77.9% experienced cognitive worsening; 44.1% met the study definition of cognitive progression independent of relapse activity. Memory CII increased significantly over time in the whole cohort (p = 0.003), whereas the phenotype-by-time interaction was not significant for Memory CII (p = 0.546), Executive CII (p = 0.211), or Total CII (p = 0.293). After Holm correction, the increase in Memory CII remained significant in baseline RRMS (+1.59; adjusted p = 0.007), but not in baseline SPMS (+1.40; adjusted p = 0.072) or PPMS (+0.57; adjusted p = 0.467). Eleven patients (32.4% of baseline RRMS) transitioned to SPMS and were retained in the baseline RRMS group for the primary longitudinal analyses. Their mean \u0394EDSS was +1.91. Conclusions: Cognitive and motor progression represent partially distinct dimensions of MS evolution. Memory was the cognitive domain showing the clearest longitudinal worsening, particularly among patients classified as RRMS at baseline, while the magnitude of cognitive change did not differ significantly between baseline phenotypes.<\/jats:p>","DOI":"10.3390\/jcm15197627","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:10:48Z","timestamp":1790932248000},"page":"7627","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multidomain Cognitive Decline and Motor Disability in Multiple Sclerosis: A Retrospective Cohort Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7181-5627","authenticated-orcid":false,"given":"Giuseppe","family":"Romano","sequence":"first","affiliation":[{"name":"Multiple Sclerosis Center, UOSD Second Neurology, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Cropano","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, UOSD Second Neurology, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"},{"name":"Department of Health Sciences, \u201cMagna Graecia\u201d University of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0790-892X","authenticated-orcid":false,"given":"Mario","family":"Fordellone","sequence":"additional","affiliation":[{"name":"Medical Statistics Unit, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Raimo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, \u201cMagna Graecia\u201d University of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1125-6779","authenticated-orcid":false,"given":"Cinzia","family":"Coppola","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, UOSD Second Neurology, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Archetto","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, UOSD Second Neurology, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Ammendola","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, UOSD Second Neurology, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Malangone","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, UOSD Second Neurology, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8561-9720","authenticated-orcid":false,"given":"Simona","family":"Bonavita","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, UOSD Second Neurology, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Lus","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, UOSD Second Neurology, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5753-6752","authenticated-orcid":false,"given":"Elisabetta","family":"Signoriello","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, UOSD Second Neurology, University of Campania \u201cLuigi Vanvitelli\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1001\/jama.2020.26858","article-title":"Diagnosis and Treatment of Multiple Sclerosis: A Review","volume":"325","author":"McGinley","year":"2021","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1212\/WNL.0000000000000560","article-title":"Defining the clinical course of multiple sclerosis: The 2013 revisions","volume":"83","author":"Lublin","year":"2014","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e2965","DOI":"10.1212\/WNL.0000000000010909","article-title":"Pathologic correlates of the magnetization transfer ratio in multiple sclerosis","volume":"95","author":"Moccia","year":"2020","journal-title":"Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1177\/1352458516674367","article-title":"Age and disability drive cognitive impairment in multiple sclerosis across disease subtypes","volume":"23","author":"Ruano","year":"2017","journal-title":"Mult. Scler. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41582-020-0355-1","article-title":"Treatment and management of cognitive dysfunction in patients with multiple sclerosis","volume":"16","author":"DeLuca","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nrneurol.2014.139","article-title":"The link between multiple sclerosis and depression","volume":"10","author":"Feinstein","year":"2014","journal-title":"Nat. Rev. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1177\/1352458519828296","article-title":"Apathy as a herald of cognitive changes in multiple sclerosis: A 2-year follow-up study","volume":"26","author":"Raimo","year":"2020","journal-title":"Mult. Scler. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/S1474-4422(20)30277-5","article-title":"Cognitive impairment in multiple sclerosis: Clinical management, MRI, and therapeutic avenues","volume":"19","author":"Benedict","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1177\/1352458511431076","article-title":"Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)","volume":"18","author":"Langdon","year":"2012","journal-title":"Mult. Scler. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s10072-013-1558-7","article-title":"The Rao\u2019s Brief Repeatable Battery version B: Normative values with age, education and gender corrections in an Italian population","volume":"35","author":"Goretti","year":"2014","journal-title":"Neurol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1007\/s00415-012-6678-0","article-title":"Treatment of cognitive impairment in multiple sclerosis: Position paper","volume":"260","author":"Amato","year":"2013","journal-title":"J. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1007\/s00415-012-6705-1","article-title":"Cognitive impairment, health-related quality of life and vocational status at early stages of multiple sclerosis: A 7-year longitudinal study","volume":"260","author":"Ruet","year":"2013","journal-title":"J. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1177\/1352458513485981","article-title":"The effects of long-term interferon-beta-1b treatment on cognitive functioning in multiple sclerosis: A 16-year longitudinal study","volume":"19","author":"Lacy","year":"2013","journal-title":"Mult. Scler. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1212\/WNL.0000000000000885","article-title":"Neuropsychological features in childhood and juvenile multiple sclerosis: Five-year follow-up","volume":"83","author":"Amato","year":"2014","journal-title":"Neurology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/S1474-4422(22)00289-7","article-title":"Multiple sclerosis progression: Time for a new mechanism-driven framework","volume":"22","author":"Kuhlmann","year":"2023","journal-title":"Lancet Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1093\/brain\/awac016","article-title":"How patients with multiple sclerosis acquire disability","volume":"145","author":"Lublin","year":"2022","journal-title":"Brain"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"University of California, San Francisco MS-EPIC Team, Cree, B.A.C., Hollenbach, J.A., Bove, R., Kirkish, G., Sacco, S., Caverzasi, E., Bischof, A., Gundel, T., and Zhu, A.H. (2019). Silent progression in disease activity-free relapsing multiple sclerosis. Ann. Neurol., 85, 653\u2013666.","DOI":"10.1002\/ana.25463"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/S0140-6736(18)30475-6","article-title":"Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): A double-blind, randomised, phase 3 study","volume":"391","author":"Kappos","year":"2018","journal-title":"Lancet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1093\/brain\/aww173","article-title":"Defining secondary progressive multiple sclerosis","volume":"139","author":"Lorscheider","year":"2016","journal-title":"Brain"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5382","DOI":"10.1007\/s00415-022-11193-w","article-title":"Early use of high-efficacy disease modifying therapies makes the difference in people with multiple sclerosis: An expert opinion","volume":"269","author":"Filippi","year":"2022","journal-title":"J. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1177\/13524585211020296","article-title":"Differential association of cortical, subcortical and spinal cord damage with multiple sclerosis disability milestones: A multiparametric MRI study","volume":"28","author":"Valsasina","year":"2022","journal-title":"Mult. Scler. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1001\/jamaneurol.2020.4920","article-title":"Identifying the Distinct Cognitive Phenotypes in Multiple Sclerosis","volume":"78","author":"Portaccio","year":"2021","journal-title":"JAMA Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2801","DOI":"10.1111\/ene.15900","article-title":"Cognitive function in primary and secondary progressive multiple sclerosis: A multiparametric magnetic resonance imaging study","volume":"30","author":"Mistri","year":"2023","journal-title":"Eur. J. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1093\/brain\/awn030","article-title":"Regional hippocampal atrophy in multiple sclerosis","volume":"131","author":"Sicotte","year":"2008","journal-title":"Brain"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/19\/7627\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:20:35Z","timestamp":1790932835000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/19\/7627"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":24,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["jcm15197627"],"URL":"https:\/\/doi.org\/10.3390\/jcm15197627","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]}}}