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Brain Sciences
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Sleep Disorders in Parkinson’s Disease
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Sleep Disorders in Parkinson’s Disease

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neurodegenerative Diseases".

Deadline for manuscript submissions: closed (25 August 2023) | Viewed by 10117

Special Issue Editor

Dr. Salar Vaseghi

E-Mail Website1 Website2
Guest Editor
Cognitive Neuroscience Lab, Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj P.O. Box 1419815477, Iran
Interests: Parkinson’s disease; neurodegenerative disease; sleep disorders; REM sleep behavior disorder; non-motor symptoms

Special Issue Information

Dear Colleagues,

Parkinson’s disease is a chronic neurodegenerative disorder characterized by a wide range of motor symptoms, including resting tremor, rigidity, bradykinesia, and postural instability, and non-motor symptoms, including depression, anhedonia, fatigue, and apathy. Brain changes in Parkinson's disease can also lead to sleep disorders, including insomnia, restless-legs syndrome, fragmented sleep, excessive daytime sleepiness, and very vivid dreams which may cause hallucinations or confusion after waking up. Furthermore, rapid-eye-movement sleep behavior disorder (RBD) has been considered the most reliable and powerful prodromal marker of Parkinson’s disease. So far, however, sleep disorders in Parkinson's disease have been underestimated. Considering these findings and the high rate of sleep disorders in Parkinson’s disease, it is necessary to conduct more studies in this field.

We invite you to submit your papers to the Brain Sciences Special Issue “Sleep Disorders in Parkinson’s Disease”. Clinical and preclinical studies regarding the mechanisms involved in the induction of sleep disorders or different therapeutic approaches for the treatment of sleep disorders in Parkinson's disease will be accepted for review or publishing. Please make sure that your research title is within the scope of the journal, which you can check in the journal menu, and that the scope is not too broad or too narrow. The aim is to have a collection of at least 10 articles; the Special Issue may be printed in book form if this number is reached.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

1) Mechanisms involved in the induction of sleep disorders in Parkinson’s disease;

2) Therapeutic approaches for the treatment of sleep disorders in Parkinson’s disease;

3) REM sleep behavior disorder in Parkinson’s disease;

4) The relationship between sleep disorders and Parkinson’s disease.

We look forward to receiving your contributions.

Dr. Salar Vaseghi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Parkinson’s disease
  • neurodegenerative disease
  • sleep disorders
  • REM sleep behavior disorder
  • non-motor symptom
  • insomnia
  • neurodegeneration
  • treatment

Published Papers (4 papers)

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Research

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14 pages, 288 KiB  
Article
The Genetic Basis of Probable REM Sleep Behavior Disorder in Parkinson’s Disease
by Santiago Perez-Lloret, Guenson Chevalier, Sofia Bordet, Hanny Barbar, Francisco Capani, Lucas Udovin and Matilde Otero-Losada
Brain Sci. 2023, 13(8), 1146; https://doi.org/10.3390/brainsci13081146 - 30 Jul 2023
Cited by 2 | Viewed by 1344
Abstract
Patients with Parkinson’s Disease (PD) experience REM sleep behavior disorder (RBD) more frequently than healthy controls. RBD is associated with torpid disease evolution. To test the hypothesis that differential genetic signatures might contribute to the torpid disease evolution in PD patients with RBD [...] Read more.
Patients with Parkinson’s Disease (PD) experience REM sleep behavior disorder (RBD) more frequently than healthy controls. RBD is associated with torpid disease evolution. To test the hypothesis that differential genetic signatures might contribute to the torpid disease evolution in PD patients with RBD we compared the rate of genetic mutations in PD patients with or without probable RBD. Patients with a clinical diagnosis of PD in the Parkinson’s Progression Markers Initiative (PPMI) database entered the study. We excluded those with missing data, dementia, psychiatric conditions, or a diagnosis change over the first five years from the initial PD diagnosis. Probable RBD (pRBD) was confirmed by a REM Sleep Behavior Disorder Screening Questionnaire score > 5 points. Logistic regression and Machine Learning (ML) algorithms were used to relate Single Nucleotide Polymorphism (SNPs) in PD-related genes with pRBD. We included 330 PD patients fulfilling all inclusion and exclusion criteria. The final logistic multivariate model revealed that the following SNPs increased the risk of pRBD: GBA_N370S_rs76763715 (OR, 95% CI: 3.38, 1.45–7.93), SNCA_A53T_rs104893877 (8.21, 2.26–36.34), ANK2. CAMK2D_rs78738012 (2.12, 1.08–4.10), and ZNF184_rs9468199 (1.89, 1.08–3.33). Conversely, SNP COQ7. SYT17_rs11343 reduced pRBD risk (0.36, 0.15–0.78). The ML algorithms led to similar results. The predictive models were highly specific (95–99%) but lacked sensitivity (9–39%). We found a distinctive genetic signature for pRBD in PD. The high specificity and low sensitivity of the predictive models suggest that genetic mutations are necessary but not sufficient to develop pRBD in PD. Additional investigations are needed. Full article
(This article belongs to the Special Issue Sleep Disorders in Parkinson’s Disease)

Review

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40 pages, 2407 KiB  
Review
Neurological Insights into Sleep Disorders in Parkinson’s Disease
by Subramanian Thangaleela, Bhagavathi Sundaram Sivamaruthi, Periyanaina Kesika, Subramanian Mariappan, Subramanian Rashmi, Thiwanya Choeisoongnern, Phakkharawat Sittiprapaporn and Chaiyavat Chaiyasut
Brain Sci. 2023, 13(8), 1202; https://doi.org/10.3390/brainsci13081202 - 14 Aug 2023
Cited by 2 | Viewed by 3128
Abstract
Parkinson’s disease (PD) is a common multidimensional neurological disorder characterized by motor and non-motor features and is more prevalent in the elderly. Sleep disorders and cognitive disturbances are also significant characteristics of PD. Sleep is an important physiological process for normal human cognition [...] Read more.
Parkinson’s disease (PD) is a common multidimensional neurological disorder characterized by motor and non-motor features and is more prevalent in the elderly. Sleep disorders and cognitive disturbances are also significant characteristics of PD. Sleep is an important physiological process for normal human cognition and physical functioning. Sleep deprivation negatively impacts human physical, mental, and behavioral functions. Sleep disturbances include problems falling asleep, disturbances occurring during sleep, abnormal movements during sleep, insufficient sleep, and excessive sleep. The most recognizable and known sleep disorders, such as rapid-eye-movement behavior disorder (RBD), insomnia, excessive daytime sleepiness (EDS), restless legs syndrome (RLS), sleep-related breathing disorders (SRBDs), and circadian-rhythm-related sleep–wake disorders (CRSWDs), have been associated with PD. RBD and associated emotional disorders are common non-motor symptoms of PD. In individuals, sleep disorders and cognitive impairment are important prognostic factors for predicting progressing neurodegeneration and developing dementia conditions in PD. Studies have focused on RBD and its associated neurological changes and functional deficits in PD patients. Other risks, such as cognitive decline, anxiety, and depression, are related to RBD. Sleep-disorder diagnosis is challenging, especially in identifying the essential factors that disturb the sleep–wake cycle and the co-existence of other concomitant sleep issues, motor symptoms, and breathing disorders. Focusing on sleep patterns and their disturbances, including genetic and other neurochemical changes, helps us to better understand the central causes of sleep alterations and cognitive functions in PD patients. Relations between α-synuclein aggregation in the brain and gender differences in sleep disorders have been reported. The existing correlation between sleep disorders and levels of α-synuclein in the cerebrospinal fluid indicates the risk of progression of synucleinopathies. Multidirectional approaches are required to correlate sleep disorders and neuropsychiatric symptoms and diagnose sensitive biomarkers for neurodegeneration. The evaluation of sleep pattern disturbances and cognitive impairment may aid in the development of novel and effective treatments for PD. Full article
(This article belongs to the Special Issue Sleep Disorders in Parkinson’s Disease)
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28 pages, 495 KiB  
Review
Parkinson’s Disease: A Narrative Review on Potential Molecular Mechanisms of Sleep Disturbances, REM Behavior Disorder, and Melatonin
by Mohammad-Ali Samizadeh, Hamed Fallah, Mohadeseh Toomarisahzabi, Fereshteh Rezaei, Mehrsa Rahimi-Danesh, Shahin Akhondzadeh and Salar Vaseghi
Brain Sci. 2023, 13(6), 914; https://doi.org/10.3390/brainsci13060914 - 6 Jun 2023
Cited by 1 | Viewed by 2105
Abstract
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. There is a wide range of sleep disturbances in patients with PD, such as insomnia and rapid eye movement (REM) sleep behavior disorder (or REM behavior disorder (RBD)). RBD is a sleep [...] Read more.
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. There is a wide range of sleep disturbances in patients with PD, such as insomnia and rapid eye movement (REM) sleep behavior disorder (or REM behavior disorder (RBD)). RBD is a sleep disorder in which a patient acts out his/her dreams and includes abnormal behaviors during the REM phase of sleep. On the other hand, melatonin is the principal hormone that is secreted by the pineal gland and significantly modulates the circadian clock and mood state. Furthermore, melatonin has a wide range of regulatory effects and is a safe treatment for sleep disturbances such as RBD in PD. However, the molecular mechanisms of melatonin involved in the treatment or control of RBD are unknown. In this study, we reviewed the pathophysiology of PD and sleep disturbances, including RBD. We also discussed the potential molecular mechanisms of melatonin involved in its therapeutic effect. It was concluded that disruption of crucial neurotransmitter systems that mediate sleep, including norepinephrine, serotonin, dopamine, and GABA, and important neurotransmitter systems that mediate the REM phase, including acetylcholine, serotonin, and norepinephrine, are significantly involved in the induction of sleep disturbances, including RBD in PD. It was also concluded that accumulation of α-synuclein in sleep-related brain regions can disrupt sleep processes and the circadian rhythm. We suggested that new treatment strategies for sleep disturbances in PD may focus on the modulation of α-synuclein aggregation or expression. Full article
(This article belongs to the Special Issue Sleep Disorders in Parkinson’s Disease)
19 pages, 592 KiB  
Review
Melatonin as a Chronobiotic/Cytoprotective Agent in REM Sleep Behavior Disorder
by Daniel P. Cardinali and Arturo Garay
Brain Sci. 2023, 13(5), 797; https://doi.org/10.3390/brainsci13050797 - 13 May 2023
Cited by 3 | Viewed by 2967
Abstract
Dream-enactment behavior that emerges during episodes of rapid eye movement (REM) sleep without muscle atonia is a parasomnia known as REM sleep behavior disorder (RBD). RBD constitutes a prodromal marker of α-synucleinopathies and serves as one of the best biomarkers available to predict [...] Read more.
Dream-enactment behavior that emerges during episodes of rapid eye movement (REM) sleep without muscle atonia is a parasomnia known as REM sleep behavior disorder (RBD). RBD constitutes a prodromal marker of α-synucleinopathies and serves as one of the best biomarkers available to predict diseases such as Parkinson disease, multiple system atrophy and dementia with Lewy bodies. Most patients showing RBD will convert to an α-synucleinopathy about 10 years after diagnosis. The diagnostic advantage of RBD relies on the prolonged prodromal time, its predictive power and the absence of disease-related treatments that could act as confounders. Therefore, patients with RBD are candidates for neuroprotection trials that delay or prevent conversion to a pathology with abnormal α-synuclein metabolism. The administration of melatonin in doses exhibiting a chronobiotic/hypnotic effect (less than 10 mg daily) is commonly used as a first line treatment (together with clonazepam) of RBD. At a higher dose, melatonin may also be an effective cytoprotector to halt α-synucleinopathy progression. However, allometric conversion doses derived from animal studies (in the 100 mg/day range) are rarely employed clinically regardless of the demonstrated absence of toxicity of melatonin in phase 1 pharmacological studies with doses up to 100 mg in normal volunteers. This review discusses the application of melatonin in RBD: (a) as a symptomatic treatment in RBD; (b) as a possible disease-modifying treatment in α-synucleinopathies. To what degree melatonin has therapeutic efficacy in the prevention of α-synucleinopathies awaits further investigation, in particular multicenter double-blind trials. Full article
(This article belongs to the Special Issue Sleep Disorders in Parkinson’s Disease)
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