{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T06:31:45Z","timestamp":1786516305175,"version":"build-2736575974"},"reference-count":133,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Olfactory dysfunction is a common feature of several neuropathological disorders \u2013 including Alzheimer\u2019s and Parkinson\u2019s diseases \u2013 whose shared profile often includes glymphatic dysfunction, cognitive impairment, and sleep disturbances. Importantly, smell loss frequently precedes cognitive or motor symptoms by years, highlighting its potential as an early clinical marker. This article reviews mechanisms that may link olfactory dysfunction to disease development in a wide range of neuropathological diseases and advances a research-based hypothesis for a shared etiologic pathway underlying these overlapping symptoms. In particular, it examines metabolic syndrome as a possible upstream driver that promotes nasal turbinate vasodilation, disrupts nasal lymphatic drainage, and culminates in an olfactory-glymphatic syndrome. Integrating glymphatic imaging or assessment with olfactory testing, cognitive evaluation, and metabolic risk profiling \u2013 hypertension, diabetes mellitus, hyperlipidemia, and elevated body mass index \u2013 may enable earlier detection and open new avenues for prevention and novel therapeutic opportunities for neuropathological disorders.<\/jats:p>","DOI":"10.3389\/fnins.2026.1897376","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:59:50Z","timestamp":1786514390000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The olfactory-glymphatic syndrome: linking smell dysfunction, cognitive impairment and sleep disturbances in neuropathological disorders"],"prefix":"10.3389","volume":"20","author":[{"given":"William Thomas","family":"Phillips","sequence":"first","affiliation":[{"name":"Department of Radiology, UT Health San Antonio","place":["San Antonio, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce Gensberg","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Pathology, Methodist Hospital","place":["San Antonio, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.1212\/wnl.0000000000000993","article-title":"Systemic metabolism in frontotemporal dementia.","volume":"83","author":"Ahmed","year":"2014","journal-title":"Neurology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e5314","DOI":"10.1002\/nbm.5314","article-title":"Evaluation of the glymphatic system in rabbits using gadobutrol-enhanced MR cisternography with T1 and T2 mapping.","volume":"38","author":"Algin","year":"2025","journal-title":"NMR Biomed."},{"key":"B3","doi-asserted-by":"publisher","first-page":"636","DOI":"10.3389\/fnins.2020.00636","article-title":"Disrupted sleep and circadian rhythms in schizophrenia and their interaction with dopamine signaling.","volume":"14","author":"Ashton","year":"2020","journal-title":"Front. 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