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A total of 214 participants were evaluated (mAD, 45; msAD, 31; bv-FTD, 12; NFPA, 22; iNPH, 13; non-demented elderly controls, 91). The highest CSF orexin-A levels were found in iNPH patients (263.31\u2009\u00b1\u200956.89 pg\/mL). Patients affected by NFPA (210.86\u2009\u00b1\u200961.99 pg\/mL), iNPH, and msAD (173.04\u2009\u00b1\u200919.76 pg\/mL) showed higher CSF orexin-A concentrations than controls (145.18\u2009\u00b1\u200927.01pg\/mL) (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Bv-FTD (190.12\u2009\u00b1\u2009100.84 pg\/mL) and mAD (130.76\u2009\u00b1\u200921.70 pg\/mL) patients showed no significant differences in CSF orexin-A levels compared with controls. mAD patients showed also lower CSF orexin-A concentrations than all other patient groups.<\/jats:p>\n          <jats:p>In conclusion, orexin-A presents different CSF levels among neurocognitive disorders. The mechanisms underlying this difference vary and may include sleep-wake cycle impairment, behavioral disturbances, and CSF dynamics. The development of drugs that antagonize the orexin system could open a new frontier of research linking orexin neurotransmission to neurocognitive disorders.<\/jats:p>","DOI":"10.1007\/s10072-025-08148-0","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T15:10:25Z","timestamp":1744125025000},"page":"3631-3638","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cerebrospinal-fluid Orexin-A levels in different neurocognitive disorders: a comparison study"],"prefix":"10.1007","volume":"46","author":[{"given":"Susana","family":"Lozano-Tovar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Cremascoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Nuccetelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Sancesario","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Cattaldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Prina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Verde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Cappelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Bernardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola Biagio","family":"Mercuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2845-1332","authenticated-orcid":false,"given":"Claudio","family":"Liguori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"issue":"7063","key":"8148_CR1","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1038\/nature04284","volume":"437","author":"CB Saper","year":"2005","unstructured":"Saper CB, Scammell TE, Lu J (2005) Hypothalamic regulation of sleep and circadian rhythms. 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