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This study aims to compare the clinical characteristics and neural substrates of PwMS with predominantly reduced physical and mental QoL to distinguish between these patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study included 75 PwMS, of whom 56 had relapsing\u2010remitting multiple sclerosis (MS) and 19 had progressive MS. The Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) and Medical Outcomes Study Short Form\u201036 Health Survey were used to assess neuropsychological abnormalities and health\u2010related QoL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Physical and mental QoL were not correlated. In a subset of PwMS, cluster analysis revealed that either physical or mental QoL was primarily affected. Patients with reduced physical QoL (\n                      <jats:italic>n<\/jats:italic>\n                      = 9) were generally older, more likely to have a progressive disease course, and had higher EDSS scores. Imaging revealed reduced whole\u2010brain and grey matter volumes, as well as bilateral cortical atrophy in the frontal lobes, specifically in the left rostral middle frontal cortex. In contrast, patients with reduced mental QoL (\n                      <jats:italic>n<\/jats:italic>\n                      = 19) had a relapsing\u2010remitting disease course and elevated MSNQ scores. These patients exhibited an increased lesion load, T1 white matter hypointensity volume, and bilateral cortical atrophy in the temporal lobes, specifically in the right insula and left superior temporal cortex.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PwMS with predominantly reduced mental QoL exhibit distinct inflammatory changes that may contribute to disrupted connectivity and cortical atrophy in the lateral postcentral regions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71050","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T06:49:26Z","timestamp":1763794166000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Differences in the Neural Substrate for Physical and Mental Quality of Life in Patients With Multiple Sclerosis"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7170-7853","authenticated-orcid":false,"given":"Juichi","family":"Fujimori","sequence":"first","affiliation":[{"name":"Division of Neurology Tohoku Medical and Pharmaceutical University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko","family":"Nei","sequence":"additional","affiliation":[{"name":"Nursing Bureau Tohoku Medical and Pharmaceutical University Hospital  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Umezawa","sequence":"additional","affiliation":[{"name":"Department of Neurology Tohoku University Graduate School of Medicine  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Misu","sequence":"additional","affiliation":[{"name":"Department of Neurology Tohoku University Graduate School of Medicine  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2612-8948","authenticated-orcid":false,"given":"Ichiro","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Division of Neurology Tohoku Medical and Pharmaceutical University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2019.1590199"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2024.105629"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23707"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458516680750"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-821929-4.00002-0"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(00)00314-0"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000002564"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/03610927408827101"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010024\u201012524\u20109"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583\u2010018\u20100053\u20109"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010019\u201009595\u20104"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.2050"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2020.102388"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ16\u20100182"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0895\u20104356(98)00095\u2010x"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000037297"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458520972279"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csda.2006.11.025"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1216\u201021.2022"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458518803785"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1194859"},{"key":"e_1_2_14_23_1","volume-title":"The Working Brain. 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