Cerebrospinal-fluid Orexin-A levels in different neurocognitive disorders: a comparison study.

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Title: Cerebrospinal-fluid Orexin-A levels in different neurocognitive disorders: a comparison study.
Authors: Lozano-Tovar, Susana (AUTHOR), Cremascoli, Riccardo (AUTHOR), Nuccetelli, Marzia (AUTHOR), Sancesario, Giuseppe (AUTHOR), Cattaldo, Stefania (AUTHOR), Prina, Elisa (AUTHOR), Verde, Federico (AUTHOR), Cappelli, Simone (AUTHOR), Bernardini, Sergio (AUTHOR), Mercuri, Nicola Biagio (AUTHOR), Liguori, Claudio (AUTHOR)
Source: Neurological Sciences. Aug2025, Vol. 46 Issue 8, p3631-3638. 8p.
Subjects: Alzheimer's disease, Neurobehavioral disorders, Frontotemporal dementia, Sleep-wake cycle, Idiopathic diseases
Abstract: In the present study, we investigated the differences in cerebrospinal fluid (CSF) orexin-A levels among patients with different neurocognitive disorders, such as mild or moderate to severe Alzheimer's disease (AD; mAD, msAD, respectively), behavioral variants of frontotemporal dementia (bv-FTD), non-fluent primary aphasia (NFPA), and idiopathic normal pressure hydrocephalus (iNPH). 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 ± 56.89 pg/mL). Patients affected by NFPA (210.86 ± 61.99 pg/mL), iNPH, and msAD (173.04 ± 19.76 pg/mL) showed higher CSF orexin-A concentrations than controls (145.18 ± 27.01pg/mL) (p < 0.001). Bv-FTD (190.12 ± 100.84 pg/mL) and mAD (130.76 ± 21.70 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. 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. [ABSTRACT FROM AUTHOR]
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Database: Psychology and Behavioral Sciences Collection
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Abstract:In the present study, we investigated the differences in cerebrospinal fluid (CSF) orexin-A levels among patients with different neurocognitive disorders, such as mild or moderate to severe Alzheimer's disease (AD; mAD, msAD, respectively), behavioral variants of frontotemporal dementia (bv-FTD), non-fluent primary aphasia (NFPA), and idiopathic normal pressure hydrocephalus (iNPH). 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 ± 56.89 pg/mL). Patients affected by NFPA (210.86 ± 61.99 pg/mL), iNPH, and msAD (173.04 ± 19.76 pg/mL) showed higher CSF orexin-A concentrations than controls (145.18 ± 27.01pg/mL) (p < 0.001). Bv-FTD (190.12 ± 100.84 pg/mL) and mAD (130.76 ± 21.70 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. 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. [ABSTRACT FROM AUTHOR]
ISSN:15901874
DOI:10.1007/s10072-025-08148-0