Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.
This week, we would like to share several latest articles are related to Sleep Disorders and Parkinson's Disease.
Title: Association between probable REM sleep behavior disorder and increased dermal alpha-synuclein deposition in Parkinson's disease
Authors: K. Doppler, S. Mammadova, A. Kuzkina, K. Reetz, J. Michels, W. Hermann, M. Sommerauer, J. Volkmann, W.H. Oertel, A. Janzen, C. Sommer
Type: Short Communication
●Dermal alpha-synuclein deposition is higher in PD patients with RBD.
●Dermal alpha-synuclein deposition is similar in PD patients with RBD and isolated RBD.
●RBD may be an indicator of a strong involvement of peripheral nerves in PD.
Many patients with Parkinson's disease suffer from REM sleep behavior disorder, potentially preceding the onset of motor symptoms. Phospho-alpha-synuclein is detectable in skin biopsies of patients with isolated REM sleep behavior disorder several years prior to the onset of manifest PD, but information on the association between dermal phospho-alpha-synuclein deposition and REM sleep behavior disorder in patients with manifest PD is limited. We therefore aimed to investigate the alpha-synuclein burden in dermal peripheral nerve fibers in patients with Parkinson's disease with and without REM sleep behavior disorder.
Patients with Parkinson's disease (n = 43) who had undergone skin biopsy for the immunohistochemical detection of phosphorylated alpha-synuclein were screened for REM sleep behavior disorder using RBDSQ and Mayo Sleep Questionnaire. Skin biopsies from 43 patients with isolated polysomnography-confirmed REM sleep behavior disorder were used as comparators.
Dermal alpha-synuclein deposition was more frequently found (81.8% vs. 52.4%, p = 0.05) and was more abundant (p = 0.01) in patients with Parkinson's disease suffering from probable REM sleep behavior disorder compared to patients without REM sleep behavior disorder and was similar to patients with isolated REM sleep behavior disorder (79.1%).
The phenotype of REM sleep behavior disorder is associated with high amounts of dermal alpha-synuclein deposition, demonstrating a strong involvement of peripheral nerves in patients with this non-motor symptom and may argue in favor of REM sleep behavior disorder as an indicator of a "body-predominant" subtype of Parkinson's disease.
Access this article: https://doi.org/10.1016/j.parkreldis.2022.05.010
Title: Peripheral Blood Inflammatory Cytokines are Associated with Rapid Eye Movement Sleep Behavior Disorder in Parkinson's Disease
Authors: Lan-xiang Wang, Chang Liu, Ying-qi Shao, Hong Jin, Cheng-jie Mao, Jing Chen
Type: Research Article
●CRP and LMR is associated with increased risk of PD, especially in RBD patients.
●We hypothesize that CRP and LMR can serve as biomarkers of RBD in PD patients.
Previous studies have shown the essential role of inflammation in rapid eye movement (REM) sleep behavior disorder (RBD). However, the association of RBD in Parkinson's disease (PD) with peripheral blood inflammatory cytokines is still unknown. We investigated the relationship between inflammatory cytokines and the clinical characteristics of PD patients with RBD.
A total of 153 PD patients and 36 healthy controls were included in this study, and blood plasma was collected. PD patients were classified as PD with RBD (PD-RBD, n=60) and PD without RBD (PD-nRBD, n=93). Inflammatory factor levels were compared among the control, PD-RBD, and PD-nRBD groups.
The PD-RBD group had significantly higher C-reactive protein (CRP) levels (P<0.001), monocytes (P=0.003), and neutrophil-to-lymphocyte ratio (NLR) (P<0.001), whereas this group has lower lymphocytes levels (P<0.001) and lymphocyte-to-monocyte ratio (LMR) (P<0.001) than the PD-nRBD group. Univariate and multivariate logistic regression analysis indicated that LMR (P<0.0001 odds ratio [OR]=0.424) was a protective factor, whereas CRP (P<0.001 OR=2.326) was a risk factor for the PD-RBD group. PD-RBD patients had lower Montreal Cognitive Assessment (Beijing version) (MoCA) (P<0.001) and Mini-Mental State Examination (MMSE) (P=0.039) scores than PD-nRBD patients.
Significant differences were found in inflammation levels between PD-RBD and PD-nRBD, suggesting that inflammatory factors are associated with the pathogenesis of RBD in PD patients. Thus, CRP and LMR levels may serve as biomarkers and predict the prognosis of PD patients with RBD.
Access this article: https://doi.org/10.1016/j.neulet.2022.136692
Title: Decision making under uncertainty in Parkinson's disease with Rem sleep behavior disorder
Authors: Ana Marques, Bruno Pereira, Michela Figorilli, Tiphaine Vidal, Paul Deffarges, Franck Durif, Livia Fantini
Type: Original Article
●IGT was used to assess decision making under uncertainty in PD with and without RBD.
●Decision making impairment was reported in PD with RBD vs. without RBD and controls.
●This impairment was regardless to cognitive status, disease duration and treatment.
●RBD in PD could be associated with an inability to learn from punishment or reward.
●This could explain the increased risk to develop ICDs reported in PD patients with RBD.
REM sleep behavior disorder (RBD) is associated with an increased risk to develop Impulse control disorders (ICDs) in Parkinson's disease (PD), however the mechanisms underlying this putative association are still poorly understood. Decision-making impairment, one major neuro-psychological dimension that may lead to ICDs, has been reported in idiopathic RBD, but has never been assessed in RBD associated with PD.
We aimed to assess decision-making abilities under ambiguous situations associated with the presence of RBD in PD patients.
In this cross-sectional study, 60 non-demented PD patients with (PD-RBD, n = 40) and without (PD-nRBD, n = 20) video polysomnography-confirmed RBD, and 20 healthy controls matched for gender and age were included. All subjects underwent neurological and neuropsychological examination, including Iowa Gambling task designed to asses decision-making under uncertainty.
IGT total score did not differ between groups (p = 0.851), however PD-RBD presented, more disadvantageous choices for the last blocks of IGT compared to PD-nRBD (p = 0.001) and to HC (p = 0.012). Progression of scores did not differ between HC and PD-nRBD. Multivariate analyses taking into account the value of scores at baseline, as well as the duration of PD, the duration of treatment, the presence of ICDs and MMSE confirmed those results.
Decision making under uncertainty is impaired in PD-RBD compared to PD-nRBD and healthy controls, regardless to the duration of disease, treatment, cognitive status and the presence of ICDs. This could reflect an inability to learn from punishment or reward in PD-RBD, and could explain the increased risk to develop ICDs reported in those patients.
Access this article: https://doi.org/10.1016/j.sleep.2022.01.025
Title: Sleep disturbance and health-related quality of life in Parkinson's disease: A clear correlation between health-related quality of life and subjective sleep quality
Authors: Ayumi Tsuru, Kentaro Matsui, Ayano Kimura, Takuya Yoshiike, Rei Otsuki, Kentaro Nagao, Megumi Hazumi, Tomohiro Utsumi, Michio Fukumizu, Yohei Mukai, Yuji Takahashi, Takashi Sakamoto, Kenichi Kuriyama
Type: Original Article
●Polysomnographic measures showed negligible correlation with HRQoL in PD patients.
●Subjective sleep quality was associated with both mental and physical HRQoL.
●Objective sleep fragmentation may not be well recognized in PD patients.
Comorbid insomnia and poor sleep quality in Parkinson's disease (PD) are associated with a poor health-related quality of life (HRQoL). However, the relationship between HRQoL and sleep measures obtained using polysomnography (PSG) remains unclear. We aimed to examine the association between various sleep measures and HRQoL in PD patients.
We retrospectively included patients with PD who underwent PSG and responded to self-administered questionnaires including the Pittsburgh Sleep Quality Index (PSQI) and Medical Outcomes Study 36-Item Short-Form Health Survey.
The patients' (n = 120) mean age was 67.06 (SD = 8.77) years, and their mean Hoehn and Yahr stage was 2.25 (SD = 0.78). A higher PSQI score (worse subjective sleep quality) was correlated in PSG with shorter sleep latency, less N1 sleep, and more N2 sleep. Multiple regression analysis showed that the total PSQI score correlated with both physical and mental HRQoL (p < 0.001 in both cases). However, neither type of HRQoL studied correlated with objective sleep measures, including indicators of sleep architecture, sleep-disordered breathing, and sleep related movement disorders.
Despite the association between subjective sleep quality and HRQoL, the associations between objective measures and HRQoL were negligible. Objective sleep fragmentation may not be perceived as a sleep disturbance in patients with PD, and therefore may not adversely affect their subjective health, given the paradoxical correlation between PSQI score and sleep architecture.
Access this article: https://doi.org/10.1016/j.parkreldis.2022.04.014
Title: REM sleep behavior disorder
Authors: Joshua Roland, Alon Y. Avidan
Type: Review Article
Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia distinguished by the partial to total loss of the normally occurring skeletal muscle atonia characteristically seen during REM sleep. Clinically, patients with RBD experience complex motor behaviors or vocalizations during sleep, a phenomenon recognized as dream enactment behavior (DEB). During polysomnography (PSG), people with RBD experience REM sleep without atonia (RSWA, or RWA), an electromyographic (EMG) manifestation reflecting the absence of muscle atonia.
The associated DEBs, which have the potential to be violent, may put both patients and bed partners at risk for physical injury. Examples include punching and limb flailing movements, often oriented toward a supposed intruder corresponding to dream content where patients perceive defending themselves. RBD is the only parasomnia where diagnostic polysomnography is fundamental for diagnosis, given that dream enactment is not unique to RBD, and with diagnosis requiring documentation of loss of REM-related muscle atonia. Management goals focus on improving patient and bed partner safety by implementing strategies to reduce risk by modifying the sleep environment. Pharmacotherapy typically utilizing melatonin or clonazepam may be necessary based on the frequency and the severity of DEB. RBD is a strong prognostic indicator for progression to neurodegenerative α-synucleinopathies with a high rate of phenoconversion of patients with RBD to neurological disorders such as Parkinson's disease, dementia with Lewy bodies (DLB), or multiple system atrophy. RBD may also be provoked or be unmask by antidepressant medications, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs). Disclosure of the diagnosis of RBD and the potential risk for progression to alpha-synucleinopathies is generally recommended based on the principle of transparency, but requires shared decision support considering patient's preferences and values.
Access this article: https://doi.org/10.1016/B978-0-12-822963-7.00336-4