{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T00:18:36Z","timestamp":1793837916411,"version":"4.6.1"},"reference-count":265,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The presentation of mood disorders that involve agitation and anxiety in patients with cognitive loss represent significant challenges for the care of patients with Alzheimer\u2019s disease (AD). Additional concerns rest with the rising lifespan and aging of the global population with expectations that over the next two decades more than 50 percent of the elderly population will suffer from mental health disease and at least 30 million of these individuals will also succumb to cognitive loss with AD. Although current treatments for mood disorders and cognitive loss can have a multi-modal approach with behavioral therapy, cognitive training sessions, physical exercise, nutritional care, environmental changes, and disease modifying agents, these therapies are primarily symptomatic in nature that do not halt disease progression and possess risks for further nervous system insults. Given these consideration, novel work that addresses the shared underlying pathways for mood disorders and cognitive loss with autophagy and related mechanisms of programmed cell death, aging and cellular senescence, perivascular system dysfunction, inflammatory microglial cell dynamics, oxidative stress, metabolic pathways that involve diabetes mellitus and apolipoprotein E, the gut microbiota, glucagon-like peptide-1 receptor agonism, innovative diagnostic strategies, artificial intelligence, and machine learning can offer rewarding avenues for the innovative development of therapeutic strategies that address disease onset and progression of these disorders. These pathways that oversee mood disorders and cognitive are both critical and complex in their intimate relationships and warrant in-depth knowledge of the mechanisms that can influence biological outcome for clinical translation.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1846280","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:07:54Z","timestamp":1780636074000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Agitation, Alzheimer\u2019s disease, and autophagy: mechanistic insights into aging pathways, gut microbiome, and artificial intelligence"],"prefix":"10.3389","volume":"17","author":[{"given":"Kenneth","family":"Maiese","sequence":"first","affiliation":[{"name":"Innovation and Commercialization, National Institutes of Health","place":["Bethesda, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s12035-025-05553-6","article-title":"The 4e-Bps as translational regulators in neurological disorders: Molecular mechanisms and therapeutic potential","volume":"63","author":"Baskarapantula","year":"2025","journal-title":"Mol Neurobiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1038\/s41398-025-03775-9","article-title":"Computational biological analysis reveals that Hif-1 and Foxo signaling pathways influence cognitive impairment in patients with depression","volume":"15","author":"Zhuo","year":"2025","journal-title":"Transl Psychiatry"},{"key":"B3","article-title":"Global burden of disease study 2021. 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