{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T01:14:27Z","timestamp":1789434867475,"version":"build-2803163510"},"reference-count":62,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Multiple Sclerosis Society Mentor-Based Postdoctoral Fellowship in Rehabilitation Research","award":["MB-2107\u201338295"],"award-info":[{"award-number":["MB-2107\u201338295"]}]},{"DOI":"10.13039\/100000071","name":"NIH","doi-asserted-by":"publisher","award":["R21HD106133"],"award-info":[{"award-number":["R21HD106133"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"NIH","doi-asserted-by":"publisher","award":["F31HD116491"],"award-info":[{"award-number":["F31HD116491"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R21HD106133"],"award-info":[{"award-number":["R21HD106133"]}],"id":[{"id":"https:\/\/ror.org\/044zkrt47","id-type":"ROR","asserted-by":"publisher"}]},{"award":["F31HD116491"],"award-info":[{"award-number":["F31HD116491"]}],"id":[{"id":"https:\/\/ror.org\/044zkrt47","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"NIH\/NIA Michigan Alzheimer\u2019s Disease Research Center","doi-asserted-by":"publisher","award":["P30AG072931"],"award-info":[{"award-number":["P30AG072931"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Michigan Alzheimer\u2019s Disease Center"},{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Chronological age incompletely captures neurodegenerative burden and functional vulnerability in multiple sclerosis (MS). Brain-predicted age difference (Brain-PAD; predicted minus chronological age) provides an MRI-derived index of accelerated brain aging, but links to mobility and real-world behavior remain unclear. Forty-three adults with MS completed structural MRI, mobility testing, and six months of free-living physical activity monitoring. Brain age was estimated using PyBrainAge applied to FreeSurfer-derived cortical thickness and subcortical volumes. Hierarchical regressions tested whether Brain-PAD explained additional variance in mobility (Mini-BESTest total and subscores; forward\/backward walking velocity) and moderate-to-vigorous physical activity (MVPA) beyond age and disability (PDDS). Predicted brain age exceeded chronological age (Brain-PAD = 8.4 \u00b1 11.1 years; p &lt; 0.001). After accounting for age and PDDS, Brain-PAD explained additional variance in Mini-BESTest total (\u0394R2 = 0.05, p = 0.042) and anticipatory control (\u0394R2 = 0.08, p = 0.034), with a trend for sensory orientation. Brain-PAD was not associated with walking velocity beyond PDDS. Higher Brain-PAD was associated with lower MVPA (\u03b2 = \u22120.91, p = 0.005) and explained additional variance (\u0394R2 = 0.19). Brain-PAD is elevated in MS and relates to balance control and real-world physical activity beyond age and disability, highlighting its potential to identify functional vulnerability.<\/jats:p>","DOI":"10.3390\/s26082442","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T10:14:46Z","timestamp":1776334486000},"page":"2442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Accelerated Brain Aging Identifies Functional Vulnerability Beyond Chronological Age in Multiple Sclerosis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1151-7000","authenticated-orcid":false,"given":"Patrick G.","family":"Monaghan","sequence":"first","affiliation":[{"name":"Department of Health Care Sciences, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6546-5752","authenticated-orcid":false,"given":"Taylor N.","family":"Takla","sequence":"additional","affiliation":[{"name":"Translational Neuroscience Program, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1908-5588","authenticated-orcid":false,"given":"James H.","family":"Cole","sequence":"additional","affiliation":[{"name":"Hawkes Institute, Department of Computer Science, University College London, London WC1V 6LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4548-1077","authenticated-orcid":false,"given":"Nora E.","family":"Fritz","sequence":"additional","affiliation":[{"name":"Department of Health Care Sciences, Wayne State University, Detroit, MI 48201, USA"},{"name":"Translational Neuroscience Program, Wayne State University, Detroit, MI 48201, USA"},{"name":"Department of Neurology, Wayne State University, Detroit, MI 48201, USA"},{"name":"Institute for Gerontology, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1029","DOI":"10.1212\/WNL.0000000000007035","article-title":"The Prevalence of MS in the United States: A Population-Based Estimate Using Health Claims Data","volume":"92","author":"Wallin","year":"2019","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1212\/WNL.0b013e3181cf6ec0","article-title":"The Rising Prevalence and Changing Age Distribution of Multiple Sclerosis in Manitoba","volume":"74","author":"Marrie","year":"2010","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1097\/WCO.0000000000000695","article-title":"The Changing Course of Multiple Sclerosis: Rising Incidence, Change in Geographic Distribution, Disease Course, and Prognosis","volume":"32","author":"Magyari","year":"2019","journal-title":"Curr. 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