Eye Movement Sleep Behavior Disorder Research Articles

Progression trajectories from prodromal to overt synucleinopathies: a longitudinal, multicentric brain [18F]FDG-PET study

The phenoconversion trajectory from idiopathic/isolated Rapid eye movement (REM) sleep behavior disorder (iRBD) towards either Parkinson’s Disease (PD) or Dementia with Lewy Bodies (DLB) is currently uncertain. We investigated the capability of baseline brain [18F]FDG-PET in differentiating between iRBD patients eventually phenoconverting to PD or DLB, by deriving the denovoPDRBD-related pattern (denovoPDRBD-RP) from 32 de novo PD patients; and the denovoDLBRBD-RP from 30 de novo DLB patients, both with evidence of RBD at diagnosis. To explore [18F]FDG-PET phenoconversion trajectories prediction power, we applied these two patterns on a group of 115 iRBD patients followed longitudinally. At follow-up (25.6 ± 17.2 months), 42 iRBD patients progressed through overt alpha-synucleinopathy (21 iRBD-PD and 21 iRBD-DLB converters), while 73 patients remained stable at the last follow-up visit (43.2 ± 27.6 months). At survival analysis, both patterns were significantly associated with the phenoconversion trajectories. Brain [18F]FDG-PET is a promising biomarker to study progression trajectories in the alpha-synucleinopathy continuum.

Cognitive Impact of β-Amyloid Load in the Rapid Eye Movement Sleep Behavior Disorder-Lewy Body Disease Continuum.

Rapid eye movement sleep behavior disorder (RBD) is linked to the diffuse-malignant subtype and higher cognitive burden in Lewy body disease (LBD). This study explores brain β-amyloid deposition and its association with cognitive decline across the RBD-LBD continuum. Patients with isolated RBD (iRBD), Parkinson's disease with probable RBD (PDRBD), and dementia with Lewy bodies with probable RBD (DLBRBD) underwent 18F-florbetaben positron emission tomography, 3T magnetic resonance imaging scans, and comprehensive neuropsychological assessments. Subjects were categorized as cognitively normal (NC), mild cognitive impairment (MCI), or dementia. Global and regional standardized uptake value ratios (SUVR) were estimated in predefined cognitive volumes of interest (VOI) derived from voxel-wise comparison analysis among the cognitive groups, namely the prefrontal, parietal, precentral cortices, lingual gyrus, and supplementary motor area. Generalized linear models assessed the relationship between 18F-florbetaben SUVRs and neuropsychological testing, adjusting for age and sex. Subgroup analysis focused on the polysomnography-confirmed iRBD-continuum subset (n = 41) encompassing phenoconverters and nonconverters in our prospective iRBD cohort. Eighty-six subjects were classified as follows: 14 NC, 54 MCI, and 18 dementia. The proportion of positive β-amyloid scans increased with advanced cognitive stages (P = 0.038). β-Amyloid signals in cognitive VOIs were elevated in subgroups showing impairment in Trail-Making Test B (TMT-B). A linear association between TMT-B z score and global cortical β-amyloid levels was observed in the iRBD-continuum subset (P = 0.013). Cortical β-amyloid accumulates with declines in executive function within the RBD-LBD continuum. TMT-B performance may be a useful marker associating with β-amyloid load, particularly in the iRBD population. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Cholinergic dysfunction in isolated rapid eye movement sleep behaviour disorder links to impending phenoconversion.

Most patients with isolated rapid eye movement sleep behaviour disorder (iRBD) progress to a parkinsonian alpha-synucleinopathy. However, time to phenoconversion shows great variation. The aim of this study was to investigate whether cholinergic and dopaminergic dysfunction in iRBD patients was associated with impending phenoconversion. Twenty-one polysomnography-confirmed iRBD patients underwent baseline 11C-donepezil and 6-Fluoro-(18F)-l-3,4-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET). Potential phenoconversion was monitored for up to 8 years. PET images were analysed according to patients' diagnoses after 3 and 8 years using linear regression. Time-to-event analysis was made with Cox regression, dividing patients into low and high tracer uptake groups. Follow-up was accomplished in 17 patients. Eight patients progressed to either Parkinson's disease (n = 4) or dementia with Lewy bodies (n = 4), while nine remained non-phenoconverters. Compared with non-phenoconverters, 8-year phenoconverters had lower mean 11C-donepezil uptake in the parietal (p = 0.032) and frontal cortex (p = 0.042), whereas mean 11C-donepezil uptake in 3-year phenoconverters was lower in the parietal cortex (p = 0.005), frontal cortex (p = 0.025), thalamus (p = 0.043) and putamen (p = 0.049). Phenoconverters within 3 years and 8 years had lower 18F-DOPA uptake in the putamen (p < 0.001). iRBD patients with low parietal 11C-donepezil uptake had a 13.46 (95% confidence interval 1.42;127.21) times higher rate of phenoconversion compared with those with higher uptake (p = 0.023). iRBD patients with low 18F-DOPA uptake in the most affected putamen were all phenoconverters with higher rate of phenoconversion (p = 0.0002). These findings suggest that cortical cholinergic dysfunction, particularly within the parietal cortex, could be a biomarker candidate for predicting short-term phenoconversion in iRBD patients. This study aligns with previous reports suggesting dopaminergic dysfunction is associated with forthcoming phenoconversion.

Daily Life Experiences of People with Dementia with Lewy Bodies: A Qualitative Study

Dementia with Lewy bodies (DLB) is the second most common cause of dementia and is associated with unique difficulties due to its characteristic symptoms. This study aimed to identify daily life changes experienced by people with DLB due to characteristic symptoms other than visual hallucinations. Semi-structured interviews and content analyses were conducted on 13 people with DLB and their 17 family members. Qualitative content analysis identified three categories of difficulties experienced by people with DLB in daily life: body discomfort, obstacles in daily life, and psychological pain. Participants experienced not only physical changes due to symptoms such as cognitive fluctuations, parkinsonism, and rapid eye movement sleep behavior disorder but also psychological pain related to daily life difficulties. This suggests the need for care that appreciates the unique experiences of people with DLB and includes psychological care to develop appropriate individual coping strategies, rather than focusing solely on alleviating physical symptoms.

Urodynamic study and its correlation with cardiac meta-iodobenzylguanidine (MIBG) in body-first and brain-first subtypes of Parkinson's disease.

Lower urinary tract symptoms (LUTS) are frequently observed in patients with Parkinson's disease (PD), but the underlying mechanism remains elusive. The concept of "body-first" and "brain-first" subtypes in PD has been proposed, but the correlation of PD subtype with LUTS remains unclear. We aimed to investigate the disparities in urological dysfunctions between body-first and brain-first subtypes of PD using urodynamic studies (UDS). We reviewed patients with PD (disease duration <3 years) who had undergone UDS and completed urological questionnaires (Overactive Bladder Symptom Score [OABSS] and International Prostate Symptom Score [IPSS]) and a voiding diary. Patients were categorized as having body-first or brain-first PD based on cardiac sympathetic denervation (CSD) using cardiac meta-iodobenzylguanidine (MIBG) uptake and the presence of rapid eye movement sleep behavior disorder (RBD), assessed using a questionnaire (PD with CSD and RBD indicating the body-first subtype). A total of 55 patients with PD were categorized into body-first PD (n = 37) and brain-first PD (n = 18) groups. The body-first PD group exhibited smaller voiding volume and first desire volume (FDV) than the brain-first PD group (p < 0.05 in both). Also, the body-first PD group had higher OABSS and IPSS scores, and higher prevalence of overactive bladder diagnosed by OABSS, compared to the brain-first PD group. In multiple linear regression, cardiac MIBG uptake was positively correlated with FDV and voiding volume andnegatively correlated with OABSS and IPSS (p < 0.05 in all). Patients with the body-first PD subtype exhibited more pronounced overactive bladder symptoms and impaired storage function in the early stage of disease. Additionally, cardiac MIBG was significantly associated with urological dysfunction.

Temporal progression of sleep electroencephalography features in isolated rapid eye movement sleep behaviour disorder.

Previous studies indicated that patients with isolated rapid eye movement (REM) sleep behaviour disorder (iRBD) exhibit alterations in spectral electroencephalographic (EEG), spindle, and slow-wave features. As it is currently unknown how these EEG features evolve over time, this study aimed to evaluate their temporal progression in patients with iRBD in comparison to controls. We included 23 patients with iRBD and 23 controls. Two polysomnographies (baseline and follow-up) were recorded with a mean (standard deviation) interval of 4.0 (2.5) years and were automatically analysed for sleep stages, spectral bandpower, spindles, and slow waves. We used linear models to evaluate differences at each time point, and linear mixed-effects models to analyse differences in temporal progression between the groups. At baseline, patients with iRBD presented EEG slowing both in REM (expressed as significantly reduced α-bandpower and increased δ-bandpower in frontal channels) and in non-REM (NREM) sleep (significantly increased slow-to-fast ratio in central channels). These differences vanished at follow-up. In both REM and NREM sleep, γ-bandpower was increased at follow-up in patients with iRBD, resulting in significantly different temporal progression between groups (in occipital channels during REM sleep and frontal channels during NREM sleep). Relative power of sleep spindles was significantly higher at baseline in patients with iRBD in frontal channels, but we observed a significant reduction over time in central channels. Finally, slow waves were significantly shorter in patients with iRBD at both time-points. Our results underscore the need of considering longitudinal data when analysing sleep EEG features in patients with iRBD. The observed temporal changes as markers of progression of neurodegeneration require further investigations.

Contribution of basal ganglia activity to REM sleep disorder in Parkinson’s disease

BackgroundRapid eye movement (REM) sleep behaviour disorder (RBD) is one of the most common sleep problems and represents a key prodromal marker in Parkinson’s disease (PD). It remains unclear whether...

Research Progress on the Relationship between Parkinson's Disease and REM Sleep Behavior Disorder.

An individual's quality of life is greatly affected by Parkinson's disease (PD), a prevalent neurological degenerative condition. Rapid eye movement (REM) sleep behavior disorder (RBD) is a prominent non-motor symptom commonly associated with PD. Previous studies have shown a close relationship between PD and RBD. In addition to being a prodromal symptom of PD, RBD has a major negative impact on the prognosis of PD patients. This intrinsic connection indicates that there is a bidirectional relationship between PD and RBD. This paper provides a comprehensive review of the pathological mechanism related to PD and RBD, including the α-synuclein pathological deposition, abnormal iron metabolism, neuroinflammation, glymphatic system dysfunction and dysbiosis of the gut microbiota. Increasing evidence has shown that RBD patients have the same pathogenic mechanisms that underlie PD, but relatively little research has been done on how RBD contributes to PD progression. Therefore, a more thorough investigation is warranted to characterise how RBD affects the course of PD, in order to prepare for future therapeutic trials.

Orthostatic Hypotension: a clinical marker for the body-first subtype of patients with Parkinson’s Disease

Our study aimed to investigate the clinical characteristics of PD patients stratified by OH status before and after levodopa challenge to explore the hypothesis that OH might serve as a clinical marker for the body-first subtype of PD. Supine and standing blood pressure were measured in a large cross-sectional cohort of PD patients at the OFF status before and after levodopa challenge test (LCT). Based on OH status, patients were divided into three groups: spontaneous OH (SOH), only levodopa-induced OH (LOH) and non-OH (NOH). Clinical characteristics and associated factors were compared among the groups. A total of 928 patients with a mean age of 62.4 years and average disease duration of 7.9 years were included. There were 224 (24.1%) patients with SOH, 321 (34.6%) with LOH, and 383 (41.3%) with NOH. Compared to NOH, both SOH and LOH were associated with older age, motor fluctuations, and probable rapid eye movement sleep behavior disorder (pRBD). In addition, OH was more associated with cardiovascular and digestive dysfunction, disease severity and worse quality of life. Results of the current study suggest that PD patients developed OH which is more likely to comorbid with RBD, severe autonomic dysfunction and motor fluctuations, consistent with the body-first subtype of PD.

REM sleep without atonia and neurocognitive function in isolated REM sleep behaviour disorder: Cross-sectional and longitudinal study.

This study investigated the relationship between rapid eye movement sleep without atonia and cognitive profiles in individuals diagnosed with isolated rapid eye movement sleep behaviour disorder, assesssing both cross-sectional associations and their link to phenoconversion in a longitudinal follow-up. Participants underwent video-polysomnography, neurological examination, neuropsychological tests and structured interviews to confirm isolated rapid eye movement sleep behaviour disorder. Rapid eye movement sleep without atonia was manually scored using the Montreal method, and participants were categorized into either high or low electromyography activity groups, based on their tonic and phasic electromyography activities. The cross-sectional study included 250 patients with isolated rapid eye movement sleep behaviour disorder, revealing that those with high tonic electromyography activity exhibited significantly lower scores in the constructional praxis recall than those with low tonic electromyography activity (p = 0.002). In the longitudinal study, 79 participants (63 isolated rapid eye movement sleep behaviour disorder and 16 phenoconversion), tracked for at least 5 years, demonstrated that high tonic electromyography activity (odds ratio: 6.14; 95% confidence interval: 1.23-30.60; p = 0.027) and lower performance on the Trail Making Test A (odds ratio: 0.23; 95% confidence interval: 0.11-0.70; p = 0.007) were associated with future phenoconversion. These results confirm the link between tonic electromyography activity and neurodegeneration in isolated rapid eye movement sleep behaviour disorder. Combining rapid eye movement sleep without atonia assessment with cognitive evaluation could serve as an early predictive marker for phenoconversion in clinical settings.

Causal Associations between Tea Consumption and Rapid Eye Movement Sleep Behavior Disorder: A Mendelian Randomization Study

Introduction: Previous studies have shown that tea consumption may have a protective effect against neurodegenerative diseases. However, the exact causal relationship between tea consumption and the precursor stages of certain neurodegenerative diseases, namely, REM sleep behavior disorder (RBD), remains unclear. To evaluate the causal association between tea consumption and RBD, we employed a Mendelian randomization study. Methods: We identified genetic instrumental variables that are significantly associated with tea consumption through genome-wide association studies (GWAS) in European populations. Bidirectional two-sample Mendelian randomization was utilized to determine the causal relationship between tea consumption and RBD, while sensitivity analyses were further employed to evaluate the robustness of the results. The multivariate Mendelian randomization method was used to assess the influence of relevant confounding factors on the results. Results: In the MR analysis using the inverse-variance weighting method, a significant causal relationship between tea consumption and RBD was observed (OR = 0.046, 95% CI: 0.004–0.563, p = 0.016). The consistency of findings across maximum likelihood, MR Pleiotropy RESidual Sum and Outlier, and multivariate MR after adjusting for potential confounding further supports this causal association. Sensitivity analyses revealed no evidence of heterogeneity or pleiotropy. Conclusions: The findings of our study demonstrate a robust causal association between tea consumption and RBD, indicating that tea consumption may serve as a protective factor against the development of RBD.

Blunted tachycardia and cardiac sympathetic denervation in isolated rapid eye movement sleep behavior disorder

BackgroundIsolated rapid eye movement sleep behavior disorder (iRBD) serves as a prodromal phase of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Blunted tachycardia (BT) during postural changes indicates neurogenic orthostatic hypotension, a marker of autonomic dysfunction. We aimed to investigate whether BT is associated with cardiac sympathetic neurogenic denervation. Additionally, we conducted a preliminary short-term follow-up to examine the potential prognostic significance of BT regarding phenoconversion and mortality.MethodsForty-three patients with iRBD at Shiga University of Medical Science Hospital underwent active standing tests to identify BT, defined by a specific ratio of decrease in systolic blood pressure to inadequate increase in heart rate after standing, and orthostatic hypotension. 123I-metaiodobenzylguanidine myocardial scintigraphy (123I-MIBG) and dopamine transporter single-photon emission computed tomography (DAT-SPECT) were performed. Participants were followed up for 3.4 ± 2.4 years for phenoconversion and 4.0 ± 2.3 years for mortality assessment, and the risk of events was analyzed using log-rank tests.ResultsAmong the 43 participants (mean age, 72.3 ± 7.9 years; 8 female), 17 met the BT criteria. We found no significant comorbidity-related differences in hypertension or diabetes between the BT(+) and BT(-) groups. Orthostatic hypotension was more prevalent in the BT(+) group than in the BT(-) group (47.1% vs 7.7%, p = 0.003). BT(+) patients were older with a lower early and delayed MIBG uptake; however, no significant differences were observed in DAT accumulation. Phenoconversion was observed in seven (41.2%) BT(+) and seven (26.9%) BT(-) patients. Three deaths were recorded in the BT(+) group (17.6%) and three in the BT(-) group (11.5%). No significant differences were observed in the risk of phenoconversion or mortality between the groups.ConclusionsWe have identified the possibility that BT reflects cardiac sympathetic neurogenic denervation in patients with iRBD. Future research is needed to elucidate the potential prognostic value of BT.

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.].

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.

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.

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.

Gait Analysis with Wearable Sensors in Isolated REM Sleep Behavior Disorder Associated with Phenoconversion: An Explorative Study.

Gait disturbance is a vital characteristic of motor manifestation in α- synucleinopathies, especially Parkinson's disease. Subtle gait alterations are present in isolated rapid eye movement sleep behavior disorder (iRBD) patients before phenoconversion; it is yet unclear, if gait analysis may predict phenoconversion. To investigate subtle gait alterations and explore whether gait analysis using wearable sensors is associated with phenoconversion of iRBD to α-synucleinopathies. Thirty-one polysomnography-confirmed iRBD patients and 33 healthy controls (HCs) were enrolled at baseline. All participants walked for a minute while wearing 6 inertial sensors on bilateral wrists, ankles, and the trunk (sternal and lumbar region). Three conditions were tested: (i) normal walking, (ii) fast walking, and (iii) dual-task walking. Decreased arm range of motion and increased gait variation (stride length, stride time and stride velocity) discriminate converters from HCs at baseline. After an average of 5.40 years of follow-up, 10 patients converted to neurodegenerative diseases (converters). Cox regression analysis showed higher value of stride length asymmetry under normal walking condition to be associated with an early conversion of iRBD to α- synucleinopathies (adjusted HR 4.468, 95% CI 1.088- 18.349, p = 0.038). Stride length asymmetry is associated with progression to α- synucleinopathies in patients with iRBD. Gait analysis with wearable sensors may be useful for screening, monitoring, and risk stratification for disease-modifying therapy trials in patients with iRBD.

The activities of daily living partially mediate the relationship between rapid eye movement sleep behavior disorder and depressive symptoms in Parkinson's disease.

A longitudinal study was conducted to investigate whether rapid eye movement sleep behavior disorder affect depression in patients with Parkinson's disease through activities of daily living. A total of 387 Parkinson's disease patients' six-year follow-up data (one follow-up per year) were obtained from the Parkinson's Progression Markers Initiative. To allow causal effects to manifest, this study increased the lag period and divided the data from the six follow-ups into two groups: wave 1 (wave refers to time points), wave 3, and wave 5 as one group, and wave 2, wave 4, and wave6 as the other group. The time interval between two time points in each group was two years. To comprehensively and deeply analyze the dynamic relationships between variables, accurately infer causal relationships, control for individual differences, and detect the stability of these relationships, this study constructed the fixed effects cross-lagged panel model (CLPM), the random effects CLPM (RE-CLPM) model, and the Equating CLPM and Equating RE-CLPM models with applied restriction conditions. Additionally, a reverse path was added to verify the reverse prediction effect. The most suitable data analysis model was selected to explore the relationships between the study variables. Furthermore, the longitudinal mediating effect of daily living activities between rapid eye movement sleep behavior disorder and depression was investigated. In the models, Equating cross-lagged panel model was the best. The lag effect was positive and significant. In wave 1, 3, 5, activities of daily living mediated 11.82% on the path from rapid eye movement sleep behavior disorder to depression; in wave 2, 4, 6, it mediated 13.13%. Therefore, attention should be paid to the treatment of activities of daily living. Longitudinal changes in activities of daily living have indirect effects on the relationship between rapid eye movement sleep behavior disorder and depression, which highlights the importance of changes in activities of daily living ability in Parkinson's disease patients with rapid eye movement sleep behavior disorder.