Decreased cerebrospinal fluid orexin levels not associated with clinical sleep disturbance in Parkinson's disease: A retrospective study

Takuya Ogawa; Yuta Kajiyama; Hideaki Ishido; Shigeru Chiba; Gajanan S Revankar; Tomohito Nakano; Seira Taniguchi; Takashi Kanbayashi; Kensuke Ikenaka; Hideki Mochizuki

doi:10.1371/journal.pone.0279747

Decreased cerebrospinal fluid orexin levels not associated with clinical sleep disturbance in Parkinson's disease: A retrospective study

PLoS One. 2022 Dec 30;17(12):e0279747. doi: 10.1371/journal.pone.0279747. eCollection 2022.

Authors

Takuya Ogawa^{1

2}, Yuta Kajiyama¹, Hideaki Ishido^{3

4}, Shigeru Chiba^{3

5}, Gajanan S Revankar¹, Tomohito Nakano⁶, Seira Taniguchi¹, Takashi Kanbayashi^{3

5}, Kensuke Ikenaka¹, Hideki Mochizuki¹

Affiliations

¹ Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan.
² Department of Neurology, Morinomiya Hospital, Osaka, Japan.
³ International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan.
⁴ Department of Neurology, Dokkyo Medical University Saitama Medical Center, Mibu, Japan.
⁵ Ibaraki Prefectural Medical Center of Psychiatry, Kasama, Japan.
⁶ Department of Neurology, Higashiosaka City Medical Center, Osaka, Japan.

Abstract

Patients with Parkinson's disease (PD) often suffer from sleep disturbances, including excessive daytime sleepiness (EDS) and rapid eye movement sleep behavior disorder (RBD). These symptoms are also experienced by patients with narcolepsy, which is characterized by orexin neuronal loss. In PD, a decrease in orexin neurons is observed pathologically, but the association between sleep disturbance in PD and cerebrospinal fluid (CSF) orexin levels is still unclear. This study aimed to clarify the role of orexin as a biomarker in patients with PD. CSF samples were obtained from a previous cohort study conducted between 2015 and 2020. We cross-sectionally and longitudinally examined the association between CSF orexin levels, sleep, and clinical characteristics. We analyzed 78 CSF samples from 58 patients with PD and 21 samples from controls. CSF orexin levels in patients with PD (median = 272.0 [interquartile range = 221.7-334.5] pg/mL) were lower than those in controls (352.2 [296.2-399.5] pg/mL, p = 0.007). There were no significant differences in CSF orexin levels according to EDS, RBD, or the use of dopamine agonists. Moreover, no significant correlation was observed between CSF orexin levels and clinical characteristics by multiple linear regression analysis. Furthermore, the longitudinal changes in orexin levels were also not correlated with clinical characteristics. This study showed decreased CSF orexin levels in patients with PD, but these levels did not show any correlation with any clinical characteristics. Our results suggest the limited efficacy of CSF orexin levels as a biomarker for PD, and that sleep disturbances may also be affected by dysfunction of the nervous system other than orexin, or by dopaminergic treatments in PD. Understanding the reciprocal role of orexin among other neurotransmitters may provide a better treatment strategy for sleep disturbance in patients with PD.

Copyright: © 2022 Ogawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers / cerebrospinal fluid
Disorders of Excessive Somnolence* / complications
Humans
Neuropeptides*
Orexins
Parkinson Disease*
Retrospective Studies
Sleep
Sleep Wake Disorders* / complications

Substances

Orexins
Neuropeptides
Biomarkers

Associated data

Dryad/10.5061/dryad.905qfttq0

Grants and funding

YK and HM reports grants (Grant number 20FC1049) from the Research Committee of Central Nervous System Degenerative Diseases, Research on Policy Planning and Evaluation for Rare and Intractable Diseases, Health, Labour and Welfare Sciences Research Grants, the Ministry of Health, Labour and Welfare, Japan (https://www.mhlw.go.jp/english/); the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. TK reports grants (Grant number JP19dm0908001, JP20dm0107162, JP21zf0127005) from AMED (https://www.amed.go.jp/), and grants (19K08037) from JSPS KAKENHI Grant-in-Aid for Scientific Research (https://www.jsps.go.jp/j-grantsinaid/); the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.