{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:58:43Z","timestamp":1785430723817,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,22]]},"group-title":"Neurology","reference-count":66,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"funder":[{"award":["21-1144MS"],"award-info":[{"award-number":["21-1144MS"]}],"id":[{"id":"https:\/\/ror.org\/00qeet526","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Progressive structural brain changes are a hallmark of neurodegenerative conditions like Alzheimer\u2019s disease (AD), frontotemporal dementia (FTD), multiple sclerosis (MS), and Parkinson\u2019s disease (PD). The brain-predicted age difference (brain-PAD) has emerged as a promising biomarker to quantify these alterations, yet its unique clinical contribution relative to conventional measures of global brain atrophy such as the brain parenchymal fraction (BPF) remains underexplored.<\/jats:p>\n                <jats:p>In this transdiagnostic study across AD, FTD, MS, and PD, we systematically evaluated brain-PAD\u2019s capacity to distinguish patients from controls, its cross-sectional and longitudinal associations with cognition, and its voxel-wise structural correlates. We benchmarked brain-PAD against BPF to determine its added explanatory value.<\/jats:p>\n                <jats:p>Brain-PAD successfully distinguished patients from controls, adding to BPF alone, in AD, FTD, and MS, but not PD. Across disorders, higher brain-PAD correlated with worse cognition, showing clear added value beyond BPF particularly in AD and MS. Baseline brain-PAD also independently predicted subsequent cognitive changes in AD, FTD, and MS, over and above BPF. Voxel-wise analyses revealed spatial features underlying brain-PAD including, beyond global tissue loss, specific regional atrophy matching each disease\u2019s characteristic pattern.<\/jats:p>\n                <jats:p>Collectively, these findings demonstrate that brain-PAD is a clinically meaningful, transdiagnostic biomarker of neurodegeneration that complements conventional volumetric measures like the BPF.<\/jats:p>","DOI":"10.64898\/2026.07.21.26358569","type":"posted-content","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T02:20:11Z","timestamp":1784773211000},"source":"Crossref","is-referenced-by-count":0,"title":["The value of brain age as a transdiagnostic biomarker of neurodegeneration"],"prefix":"10.64898","author":[{"given":"Lonneke","family":"Bos","sequence":"first","affiliation":[{"name":"MS Center Amsterdam, Amsterdam UMC location Vrije Universiteit Amsterdam, Radiology and Nuclear Medicine, De Boelelaan 1117, Amsterdam, The Netherlands"},{"name":"Amsterdam 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