Sleep Behavior Disorder Research Articles

Acetyl-DL-leucine in two individuals with REM sleep behavior disorder improves symptoms, reverses loss of striatal dopamine-transporter binding and stabilizes pathological metabolic brain pattern—case reports

Isolated REM Sleep Behavior Disorder (iRBD) is considered a prodrome of Parkinson’s disease (PD). We investigate whether the potentially disease-modifying compound acetyl-DL-leucine (ADLL; 5 g/d) has an effect on prodromal PD progression in 2 iRBD-patients. Outcome parameters are RBD-severity sum-score (RBD-SS-3), dopamine-transporter single-photon emission computerized tomography (DAT-SPECT) and metabolic “Parkinson-Disease-related-Pattern (PDRP)”-z-score in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). After 3 weeks ADLL-treatment, the RBD-SS-3 drops markedly in both patients and remains reduced for >18 months of ADLL-treatment. In patient 1 (female), the DAT-SPECT putaminal binding ratio (PBR) decreases in the 5 years pretreatment from normal (1.88) to pathological (1.22) and the patient’s FDG-PET-PDRP-z-score rises from 1.72 to 3.28 (pathological). After 22 months of ADLL-treatment, the DAT-SPECT-PBR increases to 1.67 and the FDG-PET-PDRP-z-score stabilizes at 3.18. Similar results are seen in patient 2 (male): his DAT-SPECT-PBR rises from a pretreatment value of 1.42 to 1.72 (close to normal) and the FDG-PET-PDRP-z-score decreases from 1.02 to 0.30 after 18 months of ADLL-treatment. These results support exploration of whether ADLL may have disease-modifying properties in prodromal PD.

Severe Sleep Disturbances in Persons With Dementia With REM Sleep Behavior Disorder and Family Caregivers: A Mixed Methods Study.

Coexisting dementia and rapid eye movement sleep behavior disorder (RBD) can negatively impact persons with dementia (PWD) and their family caregivers. Little research has investigated the relationship of sleep disturbance (i.e., RBD) in PWD-caregiver dyads who live together. Thus, we aimed to examine the impact of RBD symptoms on sleep quality of PWD and their family caregivers and describe sleep interrelationships. This mixed methods study analyzed qualitative and quantitative data (wearable devices, semi-structured interviews, sleep diaries, and sleep quality surveys). Two dyads' sleep parameters and sleep experiences are reported. Findings demonstrated that RBD symptoms in PWD affected sleep quality negatively (frequent awakening during the night and shortened deep sleep). Current findings highlight the importance of RBD assessment and management for PWD, as it could help improve caregivers' and PWDs' sleep quality and well-being. [Research in Gerontological Nursing, 17(5), 247-255.].

Outcomes of surgery for inflammatory bowel disease among patients with psychiatric disorders

BackgroundPsychiatric disorders (PDs) are common among patients with inflammatory bowel disease (IBD). Brain-gut dysfunction and psychotropic medications may have adverse effects on postoperative outcomes in patients with IBD. This study aimed to evaluate the association between PD and outcomes after surgery for IBD. MethodsThis was a retrospective study of adult patients with IBD who underwent small bowel, colon, or rectal resection in the 2016 to 2021 Nationwide Readmissions Database. PDs, including psychotic, mood, anxiety, eating, sleep, personality, and childhood-onset behavioral disorders, were identified. Records about colorectal cancer were excluded. Multivariate regressions were used to examine the association of PD with outcomes. ResultsOf 81,955 patients included in the study, 21,800 (26.6%) had PDs. On risk adjustment, PD was associated with significantly increased postoperative ileus (adjusted odds ratio [AOR], 1.11; 95% CI, 1.03–1.19), length of stay (β, +1.4 days; 95% CI, 1.1–1.7), and costs (β, +$2100; 95% CI, $1200-$3100) compared with no PD. In addition, patients with PDs experienced increased odds of nonhome discharge (AOR, 1.23; 95% CI, 1.12–1.34) and 30-day readmission (AOR, 1.32; 95% CI, 1.22–1.43). Over the study period, the prevalence of PDs significantly increased from 24.3% to 28.5% (P < .001), along with an increase in the rates of ileus among patients with PDs (8.1%−15.8%; P < .001). ConclusionPD is associated with a significantly greater burden of adverse clinical and financial outcomes after IBD operations. Given the growing prevalence of mental health conditions among patients with IBD, further efforts to optimize preoperative psychiatric care may enhance the quality of colorectal surgery.

REM and NREM Sleep Parasomnia in Anti-NMDA Receptor Encephalitis.

Encephalitis with anti-N-methyl-d-aspartate receptor antibodies (anti-NMDARe) is a rare disorder characterized by cognitive impairment, psychosis, seizures, and abnormal movements. Abnormal behaviors during REM sleep have not been described in anti-NMDARe. Patients were monitored by video-polysomnography on a first night followed by multiple sleep latency tests and 18 hours of bed rest. Two patients with anti-NMDARe developed during the acute and postacute phase parasomnias including REM sleep behavior disorder and continuous finalistic quiet gesturing during a mixed N2/R sleep. The parasomnia disorder was improved by gabapentin and clonazepam. Video-polysomnography avoids misdiagnosing these parasomnia behaviors for seizure or movement disorders and allows adequate treatment.

Difference in gut microbial dysbiotic patterns between body-first and brain-first Parkinson's disease

BackgroundThis study aims to identify distinct microbial and functional biomarkers characteristic of body-first or brain-first subtypes of Parkinson's disease (PD). This could illuminate the unique pathogenic mechanisms within these subtypes. MethodsIn this cross-sectional study, we classified 36 well-characterized PD patients into body-first, brain-first, or undetermined subtypes based on the presence of premotor REM sleep behavior disorder (RBD) and cardiac meta-iodobenzylguanidine (MIBG) uptake. We then conducted an in-depth shotgun metagenomic analysis of the gut microbiome for each subtype and compared the results with those from age- and sex-matched healthy controls. ResultsSignificant differences were found in the gut microbiome of body-first PD patients (n = 15) compared to both brain-first PD patients (n = 9) and healthy controls. The gut microbiome in body-first PD showed a distinct profile, characterized by an increased presence of Escherichia coli and Akkermansia muciniphila, and a decreased abundance of short-chain fatty acid-producing commensal bacteria. These shifts were accompanied by a higher abundance of microbial genes associated with curli protein biosynthesis and a lower abundance of genes involved in putrescine and spermidine biosynthesis. Furthermore, the combined use of premotor RBD and MIBG criteria was more strongly correlated with these microbiome differences than the use of each criterion independently. ConclusionsOur findings highlight the significant role of dysbiotic and pathogenic gut microbial alterations in body-first PD, supporting the body-first versus brain-first hypothesis. These insights not only reinforce the gut microbiome's potential as a therapeutic target in PD but also suggest the possibility of developing subtype-specific treatment strategies.

Machine Learning Predicts Phenoconversion from Polysomnography in Isolated REM Sleep Behavior Disorder.

Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of alpha-synucleinopathies. This study aimed at developing a fully-automated machine learning framework for the prediction of phenoconversion in patients with iRBD by using data recorded during polysomnography (PSG). A total of 66 patients with iRBD were included, of whom 18 converted to an overt alpha-synucleinopathy within 2.7 ± 1.0 years. For each patient, a baseline PSG was available. Sleep stages were scored automatically, and time and frequency domain features were derived from electromyography (EMG) and electroencephalography (EEG) signals in REM and non-REM sleep. Random survival forest was employed to predict the time to phenoconversion, using a four-fold cross-validation scheme and by testing several combinations of features. The best test performances were obtained when considering EEG features in REM sleep only (Harrel's C-index: 0.723 ± 0.113; Uno's C-index: 0.741 ± 0.11; integrated Brier score: 0.174 ± 0.06). Features describing EEG slowing had high importance for the machine learning model. This is the first study employing machine learning applied to PSG to predict phenoconversion in patients with iRBD. If confirmed in larger cohorts, these findings might contribute to improving the design of clinical trials for neuroprotective treatments.

Clinical assessment and striatal dopaminergic activity in healthy controls and patients with Parkinson's disease: a Bayesian approach.

We aimed to evaluate correlations between striatal dopamine transporter (DAT) uptake and clinical assessments in both patients with Parkinson's disease (PD) and healthy controls. This study enrolled 193 healthy controls, and 581 patients with PD. They underwent various clinical assessments and 123I-FP-CIT SPECT scans. After reconstruction, attenuation correction, and normalization of SPECT images, counts were measured from the bilateral caudate and putamen, and the occipital cortex for reference. Count densities for each region were extracted and used to calculate striatal binding ratios (SBRs) for each striatal region. SBR is calculated as (target region/reference region)-1. After logarithmic transformation of striatal SBRs, we analyzed the effects of clinical assessments on striatal SBRs using Bayesian hierarchical modeling. MDS-UPDRS total score, part I, part II, part III, Epworth Sleepiness Scale, REM sleep behavior disorder screening questionnaire, SCOPA-AUT total score were negatively associated with striatal SBR in patients with PD. Also, HVLT recognition discrimination was positively associated with striatal SBR in both healthy controls and patients with PD. In healthy control, MDS-UPDRS part II, MOCA, SCOPA-AUT total score were positively associated with striatal SBR. We demonstrated that motor symptom, sleep disturbance, autonomic symptom, and cognition of patients with PD were associated with striatal dopaminergic activity. In healthy controls, motor symptoms, autonomic symptom, and cognition were associated with striatal dopaminergic activity, some of which showing the opposite direction with patients with PD. This result might provide new insight to underlying mechanism of dopamine system with motor and non-motor assessments.

Clinical characteristics and phenoconversion in isolated REM sleep behavior disorder: a prospective single-center study in Korea, compared with Montreal cohort.

Isolated rapid-eye movement behavior disorder (iRBD) is a prodromal synucleinopathy, but its conversion rate and subtypes can vary among different cohorts. We report the clinical characteristics and phenoconversion rate of the large single-center iRBD cohort in Korea and compared it to the Montreal cohort. This prospective cohort study examined 238 patients with polysomnography confirmed iRBD from Seoul National University Hospital (SNUH) who completed at least one follow-up evaluation. We compared the baseline and phenoconversion data of the SNUH cohort to those of 242 iRBD patients in the Montreal cohort. In the SNUH cohort, age at RBD diagnosis was similar (66.4±7.8 vs 65.6±8.4, p=0.265), but the proportion of men was lower (63.0% vs. 74.0%, p=0.001), and the duration of follow-up was shorter than that in the Montreal cohort (3.7±2.0 vs. 4.8±3.6 years, p<0.001). During follow-up, 34 (11.8%) patients in the SNUH cohort converted to neurodegenerative disease: 18 (52.9%) to Parkinson's disease, 9 (26.5%) to dementia with Lewy bodies (DLB), and 7 (20.6%) to multiple system atrophy. The conversion rate in the SNUH cohort was 15% after 3 years, 22% after 5 years, and 32% after 7 years, which was significantly lower than that of the Montreal cohort (log-rank test, p=0.002). Among phenoconversion subtype, fewer subjects in the SNUH group than in the Montreal group converted to DLB (Gray's test p=0.001). Through a comparative analysis between the SNUH and Montreal cohorts, we identified a significant difference in phenoconversion rates, particularly for DLB patients. These findings underscore the importance of further research into the underlying factors, such as racial and geographical factors contributing to such disparities.

Loss of rapid eye movement atonia in rapid eye movement sleep behaviour disorder and narcolepsy.

A reduction of physiological muscle atonia during rapid eye movement sleep is characteristic in patients with rapid eye movement sleep behaviour disorder, however, it can also be found in narcolepsy patients. We evaluated rapid eye movement sleep associated electromyographic activity to set cut-off values of rapid eye movement sleep without atonia, differentiating rapid eye movement sleep behaviour disorder and narcolepsy patients from controls to enable more precise future diagnostic criteria for these disorders. We retrospectively analysed polysomnography recordings of 16 rapid eye movement sleep behaviour disorder patients, 15 narcolepsy patients, and 19 controls. The combination of phasic and tonic electromyographic activity was recorded in the mentalis and tibialis anterior muscles and analysed in 3 second miniepochs. The cut-off value for a diagnosis of rapid eye movement sleep behaviour disorder was 17.07% (100% sensitivity, 94.7% specificity, area under the curve 0.997). For the diagnosis of narcolepsy, we yielded a cut-off value of 8.4% (86.4% sensitivity, 68.4% specificity, area under the curve 0.850). Rapid eye movement sleep without atonia significantly (p = 0.046) increased in the second night half in rapid eye movement sleep behaviour disorder patients, while it remained moderately increased in the narcolepsy group. Polysomnographic evaluation proves significantly higher rates of rapid eye movement sleep without atonia in rapid eye movement sleep behaviour disorder than in narcolepsy patients, allowing differentiation from controls with high sensitivity and specificity. An increase throughout the night is characteristic for rapid eye movement sleep behaviour disorder, whereas a consistent elevation is typical in narcolepsy patients.

Cognitive, motor, and autonomic function among individuals with serotonergic versus isolated rapid eye movement sleep behavior disorder.

Cognitive, motor, and autonomic function among individuals with serotonergic versus isolated rapid eye movement sleep behavior disorder.

CSF markers of neurodegeneration Alzheimer’s and Lewy body pathology in isolated REM sleep behavior disorder

We investigated the biomarker profile of neurodegeneration, Alzheimer’s and Lewy body pathology in the CSF of 148 polysomnography-confirmed patients with isolated REM sleep behavior disorder (IRBD), a condition that precedes Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). We assessed misfolded α-synuclein (AS) by RT-QuIC assay, amyloid-beta peptides (Aβ42 and Aβ40), phosphorylated tau (p-tau), and total tau (t-tau) by CLEIA and neurofilament light chain (NfL) by ELISA. We detected AS in 75.3% of patients, pathologically decreased Aβ42/Aβ40 ratio in 22.5%, increased p-tau in 15.5%, increased t-tau in 14.9%, and elevated NfL in 14.7%. After a mean follow-up of 2.48 ± 2.75 years, 47 (38.1%) patients developed PD (n = 24) or DLB (n = 23). At CSF collection, AS positivity [HR 4.05 (1.26–12.99), p = 0.019], mild cognitive impairment [3.86 (1.96–7.61), p < 0.001], and abnormal DAT-SPECT [2.31 (1.09–4.91), p < 0.030] were independent predictors of conversion to PD and DLB. Among the other CSF markers, only elevated p-tau/Aβ42 was predictive of conversion, although only to DLB and not as an independent variable. In IRBD, CSF AS assessment by RT-QuIC provides an added value in defining the risk of short-term conversion to PD and DLB independent of clinical and instrumental investigations. Positive Alzheimer's disease (AD) pathology markers and elevated NfL occur in a subgroup of patients, but p-tau/Aβ42 is the only marker that predicts short-term conversion to DLB. Longer follow-up is needed to assess if AD biomarkers predict the later development of PD and DLB in IRBD.

Association of CSF α-Synuclein Seeding Amplification Assay Results With Clinical Features of Possible and Probable Dementia With Lewy Bodies.

The clinical diagnosis of dementia with Lewy bodies (DLB) depends on identifying significant cognitive decline accompanied by core features of parkinsonism, visual hallucinations, cognitive fluctuations, and REM sleep behavior disorder (RBD). Hyposmia is one of the several supportive features. α-Synuclein seeding amplification assays (αSyn-SAAs) may enhance diagnostic accuracy by detecting pathologic αSyn seeds in CSF. In this study, we examine how different clinical features associate with CSF αSyn-SAA positivity in a large group of clinically diagnosed participants with DLB. Cross-sectional and longitudinal CSF samples from the multicentered observational cohort study of the DLB Consortium and similar studies within the Parkinson's Disease Biomarker Program, contributed by academic medical centers in the United States, underwent αSyn-SAA testing. Participants included those clinically diagnosed with DLB and 2 control cohorts. Associations between core DLB features and olfaction with αSyn-SAA positivity were evaluated using logistic regression. CSF samples from 191 participants diagnosed with DLB (mean age 69.9 ± 6.8, 15% female), 50 age-matched and sex-matched clinical control participants, and 49 younger analytical control participants were analyzed. Seventy-two percent (137/191) of participants with DLB had positive αSyn-SAAs vs 4% of the control groups. Among participants with DLB, those who were αSyn-SAA-positive had lower Montreal Cognitive Assessment scores (18.8 ± 5.7 vs 21.2 ± 5.2, p = 0.01), had worse parkinsonism on the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (33.8 ± 15.1 vs 25.6 ± 16.4, p = 0.001), were more likely to report RBD (114/133 [86%] vs 33/53 [62%], p < 0.0001), and had worse hyposmia on the University of Pennsylvania Smell Identification Test (UPSIT) (94/105 [90%] below 15th percentile vs 14/44 [32%], p < 0.0001). UPSIT percentile had the highest area under the curve (0.87, 95% CI 0.81-0.94) in predicting αSyn-SAA positivity and participants scoring at or below the 15th percentile of age and sex normative values had 18.3 times higher odds (95% CI 7.52-44.6) of having a positive αSyn-SAA test. Among 82 participants with longitudinal CSF samples, 81 (99%) had the same αSyn-SAA result for initial and follow-up specimens. A substantial proportion of clinically diagnosed participants with DLB had negative αSyn-SAA results. Hyposmia was the strongest clinical predictor of αSyn-SAA positivity. Hyposmia and αSyn-SAA may have utility in improving the diagnostic assessment of individuals with potential DLB. This study provided Class III evidence that CSF αSyn-SAA distinguishes patients with clinically diagnosed DLB from normal controls.

Application of Deep Learning in the Classification of EEG Signals of Parkinson's Disease Patients

This article summarizes research on classifying electroencephalogram (EEG) signals of Parkinson's disease (PD) patients using deep learning technologies. Parkinson's disease is a common neurodegenerative disorder that severely affects quality of life. EEG signals provide valuable information about brain activity. Therefore, analyzing and classifying the EEG signals of PD patients can aid in early diagnosis and treatment. The paper outlines the assessment metrics and cross-validation methods in the diagnosis of Parkinson's disease, highlighting the effectiveness of deep learning in diagnosis. The key technologies reviewed in the article include Wavelet Packet Transform (WPT) and Deep Residual Neural Networks (DRSN), with the WPT-DRSN method achieving up to 99.92% prediction accuracy in the binary classification task of PD patients. Furthermore, this method has also been applied to more complex classweweification tasks, such as categorizing PD patients, REM sleep behavior disorder patients, and healthy controls, maintaining high accuracy. When analyzing Parkinson's disease EEG with the CRNN model, the accuracy is high, but the sample size is small and the model interpretability is limited, necessitating further validation and improvement. For EEG-based PD diagnosis and classification methods, high accuracy was achieved through ICA preprocessing, CSP feature extraction, and ensemble learning classifiers. Future research should consider the integration of multimodal data fusion, deep learning, and NLP technologies, as well as the development of personalized models to enhance the accuracy of PD diagnosis.

Cortical activation in REM behavior disorder mimics voluntary movement. An electroencephalography study

ObjectivesMotor symptoms of Parkinson’s disease improve during REM sleep behavior disorder movement episodes. Our aim was to study cortical activity during these movement episodes, in patients with and without Parkinson’s disease, in order to investigate the cortical involvement in the generation of its electromyographic activity and its potential relationship with Parkinson’s disease. MethodsWe looked retrospectively in our polysomnography database for patients with REM sleep behavior disorder, analyzing fifteen patients in total, seven with idiopathic REM sleep behavior disorder and eight associated with Parkinson’s disease. We selected segments of REM sleep with the presence of movements (evidenced by electromyographic activation), and studied movement-related changes in cortical activity by averaging the electroencephalographic signal (premotor potential) and by means of time/frequency transforms. ResultsWe found a premotor potential and an energy decrease of alpha–beta oscillatory activity preceding the onset of electromyographic activity, together with an increase of gamma activity for the duration of the movement. All these changes were similarly present in REM sleep behavior disorder patients with and without Parkinson’s disease. ConclusionsMovement-related changes in electroencephalographic activity observed in REM sleep behavior disorder are similar to those observed during voluntary movements, regardless of the presence of Parkinson’s disease motor symptoms. SignificanceThese results suggest a main involvement of the cortex in the generation of the movements during REM sleep.

Major alteration of motor control during rapid eye movements sleep in mice models of sleep disorders.

Alteration of motor control during rapid eye movements (REM) sleep has been extensively described in sleep disorders, in particular in isolated REM sleep behavior disorder (iRBD) and narcolepsy type 1 (NT1). NT1 is caused by the loss of orexin/hypocretin (ORX) neurons. Unlike in iRBD, the RBD comorbid symptoms of NT1 are not associated with alpha-synucleinopathies. To determine whether the chronic absence of ORX neuropeptides is sufficient to induce RBD symptoms, we analyzed during REM sleep the EMG signal of the prepro-hypocretin knockout mice (ORX-/-), a recognized mouse model of NT1. Then, we evaluated the severity of motor alterations by comparing the EMG data of ORX-/- mice to those of mice with a targeted suppression of the sublaterodorsal glutamatergic neurotransmission, a recognized rodent model of iRBD. We found a significant alteration of tonic and phasic components of EMG during REM sleep in ORX-/- mice, with more phasic events and more REM sleep episodes without atonia compared to the control wild-type mice. However, these phasic events were fewer, shorter, and less complex in ORX-/- mice compared to the RBD-like ORX-/- mice. We thus show that ORX deficiency, as seen in NT1, is sufficient to impair muscle atonia during REM sleep with a moderate severity of alteration as compared to isolated RBD mice. As described in NT1 patients, we report a major interindividual variability in the severity and frequency of RBD symptoms in ORX-deficient mice.

GBA-AAV mitigates sleep disruptions and motor deficits in mice with REM sleep behavior disorder

Sleep disturbances, including rapid eye movement sleep behavior disorder (RBD), excessive daytime sleepiness, and insomnia, are common non-motor manifestations of Parkinson’s disease (PD). Little is known about the underlying mechanisms, partly due to the inability of current rodent models to adequately mimic the human PD sleep phenotype. Clinically, increasing studies have reported that variants of the glucocerebrosidase gene (GBA) increase the risk of PD. Here, we developed a mouse model characterized by sleep–wakefulness by injecting α-synuclein preformed fibronectin (PFF) into the sublaterodorsal tegmental nucleus (SLD) of GBA L444P mutant mice and investigated the role of the GBA L444P variant in the transition from rapid eye movement sleep behavior disorder to PD. Initially, we analyzed spectral correlates of REM and NREM sleep in GBA L444P mutant mice. Importantly, EEG power spectral analysis revealed that GBA L444P mutation mice exhibited reduced delta power during non-rapid eye movement (NREM) sleep and increased theta power (8.2–10 Hz) in active rapid eye movement (REM) sleep phases. Our study revealed that GBA L444P-mutant mice, after receiving PFF injections, exhibited increased sleep fragmentation, significant motor and cognitive dysfunctions, and loss of dopaminergic neurons in the substantia nigra. Furthermore, the over-expression of GBA-AAV partially improved these sleep disturbances and motor and cognitive impairments. In conclusion, we present the initial evidence that the GBA L444P mutant mouse serves as an essential tool in understanding the complex sleep disturbances associated with PD. This model further provides insights into potential therapeutic approaches, particularly concerning α-synuclein accumulation and its subsequent pathological consequences.

Network structure of REM sleep behavior disorder symptoms in iRBD patients

ObjectiveEmploying the REM Sleep Behavior Disorder Questionnaire-Hong Kong (RBDQ-HK) to investigate symptoms and their severity in rapid eye movement (REM) sleep behavior disorder (RBD) patients, this study delves into the construct of RBD through the RBDQ-HK and its links to depression and sleep quality. MethodsData from the RBDQ-HK, the Geriatric Depression Scale (GDS), and the Pittsburgh Sleep Quality Index (PSQI) were compiled from individuals with isolated RBD (iRBD) confirmed by polysomnography. We constructed a network analysis of the RBDQ-HK, measured the centrality of each symptom (node), conducted Exploratory Graph Analysis (EGA) to unveil the dimension structure of the questionnaire, and calculated bridge expected influence (BEI) to identifying critical bridge. Multivariate linear regression was also employed to discover relationships between RBDQ-HK dimensions and variables such as PSQI and GDS. ResultsIn our cohort of 455 iRBD patients (299 males), the items in the RBDQ-HK were divided into three dimensions: dream, movement, and SRI/violence. The symptoms identified as most central to RBD were ‘shouting or yelling in sleep’, ‘dream-enacting movements’, and ‘talking during sleep’. The highest (BEI) was ‘violent and aggressive dreams’, which has the potential to bridge three dimensions within the symptom network. Depression was significantly correlated with the movement and dream dimensions of RBD, and sleep quality was predominantly related to the dream dimension score. ConclusionOur findings verify that the principal symptoms of the RBDQ-HK align with the established diagnostic criteria and reveal a three-dimensional structure within RBD symptoms. The relationships between the RBD symptoms, depression, and sleep quality need to be identified for the effective management of RBD patients.

Polysomnographic features prior to dream enactment behaviors in isolated rapid eye movement sleep behavior disorder

ObjectiveThis study aimed to identify electroencephalogram correlates of dream enactment behaviors (DEBs) and elucidate their cortical dynamics in patients with isolated/idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). MethodsThis cross-sectional study included 15 patients with iRBD. Two REM sleep periods in routine polysomnography were compared: the 60 s preceding the DEBs (“pre-representative behavior” [preR]), and the 60 s with the least submental electromyogram activity (“background” [BG]). Six EEG frequency bands and electrooculogram were analyzed; power spectra, coherence and phase-locking values in four 15-s periods were examined to assess trends. These indices were also compared between preR and BG. ResultsCompared with BG, significantly higher delta power in the F3 channel and gamma power in the F4 and O2 channels were observed during preR. For functional connectivity, the widespread beta-band connectivity was significantly increased during preR than BG. ConclusionBefore notable REM sleep behaviors, uneven distributed higher EEG spectral power in both very low and high frequencies, and increased wide-range beta band functional connectivity, were observed over 60 s, suggesting cortical correlates to subsequent DEBs. SignificanceThis study may shed light on the pathological mechanisms underlies RBD through the routine vPSG analysis, leading to detection of DEBs.

Pain, obesity, adenosine salvage disruption, and smoking behavior mediate the effect of gut microbiota on sleep disorders: results from network Mendelian randomization and 16S rDNA sequencing.

The objective of this study is to investigate the indirect causalities between gut microbiota and sleep disorders. In stage 1, we utilized 196 gut microbiota as the exposure factor and conducted a two-sample univariable Mendelian randomization (MR) analysis on five sleep disorders: insomnia, excessive daytime sleepiness (EDS), sleep-wake rhythm disorders (SWRD), obstructive sleep apnea (OSA), and isolated REM sleep behavior disorder (iRBD). In stage 2, we validated the MR findings by comparing fecal microbiota abundance between patients and healthy controls through 16S rDNA sequencing. In stage 3, we explored the indirect pathways by which the microbiota affects sleep, using 205 gut microbiota metabolic pathways and 9 common risk factors for sleep disorders as candidate mediators in a network MR analysis. In stage 1, the univariable MR analysis identified 14 microbiota potentially influencing five different sleep disorders. In stage 2, the results from our observational study validated four of these associations. In stage 3, the network MR analysis revealed that the Negativicutes class and Selenomonadales order might worsen insomnia by increasing pain [mediation: 12.43% (95% CI: 0.47, 24.39%)]. Oxalobacter could raise EDS by disrupting adenosine reuptake [25.39% (1.84, 48.95%)]. Allisonella may elevate OSA risk via obesity promotion [36.88% (17.23, 56.54%)], while the Eubacterium xylanophilum group may lower OSA risk by decreasing smoking behavior [7.70% (0.66, 14.74%)]. Triangulation of evidence from the MR and observational study revealed indirect causal relationships between the microbiota and sleep disorders, offering fresh perspectives on how gut microbiota modulate sleep.

Quantitative EEG in Parkinson's disease: when REM sleep behavior disorder onset really matters.

Parkinson's Disease (PD) body-first subtype is characterized by prodromal autonomic symptoms and REM sleep behavior disorder (RBD), symmetric dopaminergic degeneration, and increased risk of dementia. On the other hand, the PD brain-first subtype has fewer non-motor symptoms and a milder motor phenotype. The temporal relationship between RBD onset and motor symptoms onset may differentiate these two subtypes. We aimed to investigate electrocortical differences between brain-first and body-first PD patients. PD patients with an available routinely collected EEG were retrospectively selected. RBD was diagnosed using the RBD screening questionnaire (≥ 6). According to the onset of RBD patients were classified into PD-RBDpre (RBD onset before motor symptoms) and PD-RBDpost (RBD onset after motor symptoms). Patients without RBD were classified as PD-RBD-. Presence of Mild Cognitive Impairment (MCI) was diagnosed according to the MDS criteria. EEG Spectral analysis was performed in resting state by computing the Power Spectral Density (PSD) of site-specific signal epochs for the common frequency bands (delta, theta, alpha, beta). Thirty-eight PD-RBD-, 14 PD-RBDpre and 31 PD-RBDpost patients were recruited. Comparing both global and site-specific absolute values, we found a significant trend toward beta band reduction going from PD-RBD-, PD-RBDpost and PD-RBDpre. No significant differences were found between PD-RBDpost and PD-RBD- patients. PD-RBDpre patients may represent a different subset of patients as compared to patients without RBD, while patients with later onset have intermediate EEG spectral features. Quantitative EEG may provide new hints in PD subtyping.