{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T06:51:54Z","timestamp":1782370314562,"version":"3.54.5"},"posted":{"date-parts":[[2026,6,24]]},"group-title":"Neuroscience","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,24]]},"abstract":"<jats:p>Distinguishing healthy brain aging from early neurodegenerative disruption remains a major challenge in Alzheimer's disease. Here, we used resting-state fMRI from the Alzheimer's Disease Neuroimaging Initiative to model large-scale brain-state dynamics relative to a cognitively normal aging reference. A Hidden Markov Model trained exclusively on cognitively normal adults defined latent connectivity states, and a generalized additive model estimated an age-adjusted reference trajectory of transition entropy. Mild cognitive impairment and Alzheimer's disease showed progressively greater deviation from this reference, with the strongest disruption in Alzheimer's disease. A single absolute-deviation score retained much of the predictive information contained in higher-dimensional dynamic features, supporting its use as a compact and interpretable candidate biomarker of altered brain-state organization. These findings suggest that Alzheimer's disease is associated with measurable departure from healthy dynamic brain aging, providing an interpretable framework for future longitudinal and clinically validated studies.<\/jats:p>","DOI":"10.64898\/2026.06.19.733190","type":"posted-content","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T06:44:44Z","timestamp":1782369884000},"source":"Crossref","is-referenced-by-count":0,"title":["Normative brain-state trajectories reveal deviation from healthy aging in Alzheimer's disease"],"prefix":"10.64898","author":[{"given":"Monireh","family":"Taimouri","sequence":"first","affiliation":[{"name":"University of Cincinnati"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikram","family":"Ravindra","sequence":"additional","affiliation":[{"name":"University of Cincinnati"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.06.19.733190","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T06:44:44Z","timestamp":1782369884000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.06.19.733190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":0,"URL":"https:\/\/doi.org\/10.64898\/2026.06.19.733190","relation":{},"subject":[],"published":{"date-parts":[[2026,6,24]]},"subtype":"preprint"}}