{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T02:40:31Z","timestamp":1783478431101,"version":"3.55.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["EME 11\/30\/11"],"award-info":[{"award-number":["EME 11\/30\/11"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Comorbidities including vascular risk factors can be associated with whole and regional brain atrophy in multiple sclerosis (MS). This has been examined in mixed MS cohorts in prospective or observational studies; however, the association between vascular comorbidities (VCM) in secondary progressive MS (SPMS) and brain atrophy has been less well studied. The aim was to investigate the cross\u2010sectional and longitudinal association between VCM, comorbidity burden and brain atrophy in SPMS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Post hoc analysis of 445 participants from the MS\u2013Secondary Progressive multi\u2010arm trial (MS\u2010SMART)\u2212a multi\u2010arm multicentre phase\u20102b randomised placebo\u2010controlled trial of three agents in SPMS (NCT01910259). VCM (hypertension, hyperlipidaemia) but also asthma, hypothyroidism and osteoporosis were recorded. Regional and whole brain volume (WBV), and percentage brain volume change were calculated using SIENAX and SIENA, respectively. Multiple linear regression was used to investigate the cross\u2010sectional and longitudinal relationships between VCM, overall comorbidity count and whole brain, grey matter (GM) and white matter (WM) atrophy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The cohort was predominantly female (67%), mean age 55 with median EDSS 6.0. In total, 13% and 9% had hypertension and hyperlipidaemia, respectively. In cross\u2010sectional regression models, VCM was associated with decreased cortical GM volume [(hypertension <jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u22120.30, 95%CI \u22120.54 to \u22120.06, <jats:italic>p<\/jats:italic>\u2009=\u20090.01) (hyperlipidaemia <jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u22120.37, 95%CI \u22120.64 to \u22120.09, <jats:italic>p<\/jats:italic>\u2009=\u20090.008)]; but not WBV. Having \u22652 comorbidities was also associated with decreased cortical GM volume (<jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u22120.36, 95%CI \u22120.61 to \u22120.10, <jats:italic>p<\/jats:italic>\u2009=\u20090.007). No relationship was observed between VCM\/comorbidity count and whole brain or GM atrophy rate over 96\u2009weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>People with SPMS with VCM or increased overall comorbidity burden showed reduced whole brain and especially cortical grey matter volumes, but no significant impact on subsequent 2\u2010year atrophy rate was detected.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.16586","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T09:11:10Z","timestamp":1734513070000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Vascular risk factors are associated with grey matter atrophy in secondary progressive multiple sclerosis"],"prefix":"10.1111","volume":"32","author":[{"given":"Nevin A.","family":"John","sequence":"first","affiliation":[{"name":"Department of Medicine, School of Clinical Sciences Monash University  Clayton Victoria Australia"},{"name":"Department of Neurology Monash Health  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingtong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Clinical Sciences Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floriana","family":"De Angelis","sequence":"additional","affiliation":[{"name":"Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9151-0844","authenticated-orcid":false,"given":"Jonathan","family":"Stutters","sequence":"additional","affiliation":[{"name":"Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferran","family":"Prados","sequence":"additional","affiliation":[{"name":"Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences University College London  London UK"},{"name":"Centre for Medical Image Computing (CMIC) University College London  London UK"},{"name":"e\u2010Health Center, Universitat Oberta de Catalunya  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anisha","family":"Doshi","sequence":"additional","affiliation":[{"name":"Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1953-2803","authenticated-orcid":false,"given":"Alberto","family":"Calvi","sequence":"additional","affiliation":[{"name":"Laboratory of Advanced Imaging in Neuroimmunological Diseases (imaginEM), Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2014Institut d'Investigacions Biom\u00e8diques August Pi I Sunyer (FRCB\u2010IDIBAPS)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8197-0177","authenticated-orcid":false,"given":"Thomas","family":"Williams","sequence":"additional","affiliation":[{"name":"Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Plantone","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery &amp; Neuroscience University of Siena  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh","family":"Phan","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Clinical Sciences Monash University  Clayton Victoria Australia"},{"name":"Department of Neurology Monash Health  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia A. 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