Association between <scp>cerebrospinal fluid</scp> Orexin A level and severity of <scp>rapid eye movement</scp> sleep behaviour disorder in dementia with Lewy bodies

Inagawa, Yuta; Shimizu, Soichiro; Takahashi, Naoto; Tsugawa, Akito; Hirose, Daisuke; Kanbayashi, Takashi; Imanishi, Aya; Sakurai, Hirofumi; Hanyu, Haruo; Kanetaka, Hidekazu; Hirao, Kentaro

doi:10.1111/psyg.12618

Cited by 7 publications

(26 citation statements)

References 8 publications

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“…From the remaining 23 studies, eight were excluded after abstract review, six were excluded after full-text review, and two excluded due to a lack of CSF orexin-A data. The remaining seven articles, with 432 participants, 179 with LBD and 253 controls, were finally included in the meta-analysis ( 6 , 7 , 10 , 16 , 17 , 20 , 21 ) ( Table 1 ). Two studies ( 7 , 17 ) came from the same research team and had the same control group; therefore, we analyzed them together.…”

Section: Resultsmentioning

confidence: 99%

“…To compare CSF orexin-A levels in LBD patients against NCs, five studies ( 7 , 10 , 16 , 17 , 20 ) were included (97 LBD patients vs . 92 NCs).…”

Section: Resultsmentioning

confidence: 99%

“…In other research involving LBD (including DLB, PD, or PDD) and AD, CSF orexin-A levels in LBD patients were significantly lower than those in the AD group ( 9 , 28 ). In addition, significant correlations were identified between CSF orexin-A levels and sleep disturbance severity ( 10 ) or the scores of Epworth sleepiness scale (ESS), a scale used to evaluate EDS/hypersomnia ( 7 ), after calculation. These findings on the connection between AD and LBD remain controversial.…”

Section: Discussionmentioning

confidence: 99%

“…To compare CSF orexin-A levels in LBD patients against NCs, five studies ( 7,10,16,17,20) were included (97 LBD patients vs. 92 NCs). Studies showed low heterogeneity (I 2 = 0%, P = 0.75), so a fixed-effects model was used to calculate the pooled SMD.…”

Section: Cerebrospinal Fluid Orexin-a Levels In Lewy Body Disease Vs Normal Controlsmentioning

confidence: 99%

“…Previous studies indicated that narcolepsy was linked with reduced orexin-A levels ( 8 ), and a correlation was identified between neocortical orexin-A levels and hypersomnolence in patients with DLB ( 9 ). Orexinergic overexpression may have important roles in the manifestation of rapid-eye-movement sleep behavior disorders (RBDs) in DLB; previous evidence described a significant positive correlation between RBD severity and CSF orexin-A levels ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

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Orexin-A in Patients With Lewy Body Disease: A Systematic Review and Meta-Analysis

et al. 2021

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BackgroundAbnormal orexin-A levels in cerebrospinal fluid (CSF) have been identified in Alzheimer’s disease (AD) and other neurodegenerative diseases. However, few studies have focused on Lewy body disease (LBD) and often with debatable outcomes. Thus, we performed this systematic review and meta-analysis to investigate orexin-A levels in LBD by incorporating data from different studies.MethodsWe gathered studies comparing orexin-A levels in patients with LBD and controls (including healthy controls and other dementia subtypes). In the initial search, 117 relevant articles were identified. After a selection process, seven studies, conducted in Japan, USA, Spain, Switzerland, France, Italy, and Netherlands, were chosen.ResultsIn total, 179 patients with LBD and 253 controls were included. Patients with LBD had significantly lower mean orexin-A CSF levels when compared with patients with AD [standard mean difference (SMD): −0.35, 95% confidence interval (CI): −0.70 to −0.00, Z = 1.96, P = 0.05], whereas mean orexin-A levels were significantly higher when compared with patients with frontotemporal lobar degeneration (FTLD) (SMD: 0.61, 95% CI: 0.23–0.99, Z = 3.12, P = 0.002). Orexin-A CSF levels in LBD patients were approximately equal to levels in healthy elderly individuals, whereas they were significantly decreased in LBD patients with excessive daytime sleepiness (EDS) (SMD: -0.15, 95% CI: -0.59 to 0.29, Z = 0.67, P = 0.50).ConclusionsWe showed that orexin-A levels in patients with LBD were not very different from those in normal elderly individuals, whereas they were lower than those in AD patients and higher than those in FTLD patients. The influence of hypersomnia on orexin-A levels should be carefully interpreted.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021265900.

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Section: Resultsmentioning

confidence: 99%

“…To compare CSF orexin-A levels in LBD patients against NCs, five studies ( 7 , 10 , 16 , 17 , 20 ) were included (97 LBD patients vs . 92 NCs).…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Cerebrospinal Fluid Orexin-a Levels In Lewy Body Disease Vs Normal Controlsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Orexin-A in Patients With Lewy Body Disease: A Systematic Review and Meta-Analysis

et al. 2021

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Sleep disturbances in Lewy body dementia: A systematic review

Elder

Lázár

Alfonso‐Miller

et al. 2022

Int J Geriat Psychiatry

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Background: Lewy body dementia (LBD) refers to both dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). Sleep disturbances are common in LBD, and can include poor sleep quality, excessive daytime sleepiness (EDS), and rapid eye movement behaviour disorder (RBD). Despite the high clinical prevalence of sleep disturbances in LBD, they are under-studied relative to other dementias. The aim of the present systematic review was to examine the nature of sleep disturbances in LBD, summarise the effect of treatment studies upon sleep, and highlight specific and necessary directions for future research. Methods: Published studies in English were located by searching PubMED and PSYCArticles databases (until 10 June 2022). The search protocol was preregistered in PROSPERO (CRD42021293490) and performed in accordance with PRISMA guidelines. Results: Following full-text review, a final total of 70 articles were included. These included 20 studies focussing on subjective sleep, 14 on RBD, 8 on EDS, 7 on objective sleep, and 1 on circadian rhythms. The majority of the 18 treatment studies used pharmacological interventions (n = 12), had an open-label design (n = 8), and were of low-to-moderate quality. Most studies (n = 55) included only patients with DLB. Due to the heterogeneity of the studies, we reported a narrative synthesis without meta-analysis. Conclusions: At least one form of sleep disturbance may be present in as many as 90% of people with LBD. Subjectively poor sleep quality, excessive daytime sleepiness, and RBD are more common and severe in LBD relative to other dementias.

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Orexin and Sleep Disturbances in Alpha-Synucleinopathies: a Systematic Review

Raheel,

See,

Munday

et al. 2024

Curr Neurol Neurosci Rep

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Purpose of Review Sleep disturbances are amongst most frequent non-motor symptoms of Parkinson’s Disease (PD), and they are similarly frequently reported in other alpha-syncleinopathies, such as Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA). More recently, the orexin system has been implicated in control of arousal based on salient environmental set points, and its dysregulation in sleep issues in alpha-synucleinopathies suggested by the findings from the translational animal models. However, its role in the patients with alpha-synucleinopathies remains unclear. We thus set to systematically review, and to critically assess, contemporary evidence on the association of the orexinergic system and sleep disturbances in alpha-synucleinopathies. In this systematic review, studies investigating orexin and sleep in alpha-synucleinopathies (Rapid Eye Movement (REM) Behaviour Disorder (RBD), Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA)) were identified using electronic database searches of PubMed, Web of Science and PsychINFO using MeSH terms, keywords, and title words such as “Alpha-synucleinopathies” AND “Orexin” AND “Sleep Disturbances”. Recent findings 17 studies were included in this systemic review, of which 2 studies on RBD, 10 on PD, 4 on DLB, and 1 on MSA patients. Taken together, RBD and PD studies suggest a potential adaptive increase in orexin levels in early stages of the neurodegenerative process, with reduced levels more often reported for later, more advanced stages of illness. To date, no differences in orexin levels were demonstrated between MSA patients and healthy controls. Summary There is a dearth of studies on the role of orexin levels in alpha-synucleinopathies. Moreover, significant methodologic limitations in the current body of work, including use of non-standardised research protocols and lack of prospective, multi-centre studies, disallow for any finite conclusion in regards to underlying pathomechanisms. Nonetheless, a picture of a complex, multifaceted relationship between the dysregulation of the orexinergic pathway and sleep disturbances in alpha-synucleinopathies is emerging. Hence, future studies disentangling orexinergic pathomechanisms of alpha-syncleinopathies are urgently needed to obtain a more comprehensive account of the role of orexinergic pathway in alpha-synucleinopathies. Pharmacological manipulations of orexins may have multiple therapeutic applications in treatment strategies, disease diagnosis, and might be effective for treating both motor and non-motor symptoms.

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Association between cerebrospinal fluid Orexin A level and severity of rapid eye movement sleep behaviour disorder in dementia with Lewy bodies

Cited by 7 publications

References 8 publications

Orexin-A in Patients With Lewy Body Disease: A Systematic Review and Meta-Analysis

Orexin-A in Patients With Lewy Body Disease: A Systematic Review and Meta-Analysis

Sleep disturbances in Lewy body dementia: A systematic review

Orexin and Sleep Disturbances in Alpha-Synucleinopathies: a Systematic Review

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