REM Sleep Behavior Disorder Group Research Articles

REM Sleep Behavior Disorder and Its Possible Prodromes in General Population: Prevalence, Polysomnography Findings, and Associated Factors.

To evaluate the prevalence of REM sleep behavior disorder (RBD) and its possible prodromal conditions, isolated dream enactment behavior (DEB) and isolated REM without atonia (RWA), in a general population sample, and the factors associated with diagnosis and symptom frequency. From a population-based prospective cohort in Korea, 1,075 participants (age 60.1 ± 7.0 years; range 50-80 years; men 53.7%) completed the RBD screening questionnaire (RBDSQ), a structured telephone interview for the presence and characteristics of repeated DEB, and home polysomnography (PSG). RWA was measured on submentalis EMG, including 30-second epoch-based tonic and phasic activity as well as 3-second mini-epoch-based phasic and any EMG activities. Based on the presence of repeated DEB and any EMG activity of ≥22.3%, we categorized the participants into no RBD, isolated RWA, isolated DEB, and RBD groups. RBD was diagnosed in 20 participants, isolated RWA in 133 participants, and isolated DEB in 48 participants. Sex and DEB frequency-adjusted prevalence of RBD was 1.4% (95% CI 1.0%-1.8%), isolated RWA was 12.5% (95% CI 11.3%-13.6%), and isolated DEB was 3.4% (95% CI 2.7%-4.1%). Total RBDSQ score was higher in the RBD and isolated DEB groups than in the isolated RWA and no RBD group (median 5 [interquartile range (IQR) 4-6] for RBD, median 4 [IQR 3-6] for isolated DEB, median 2 [IQR 1-3] for isolated RWA, and median 2 [IQR 1-4] for no RBD groups, p < 0.001). RBDSQ score of ≥5 had good specificity but poor positive predictive value (PPV) for RBD (specificity 84.1% and PPV 7.7%) and its prodromal conditions (specificity 85.2% and PPV 29.1%). Among the RWA parameters, any EMG activity showed the best association with the RBD and its possible prodromes (area under the curve, 0.917). Three-second mini-epoch-based EMG activity and phasic EMG activity were correlated with the frequency of DEB (standardized Jonckheere-Terpstra statistic [std. J-T static] for trend = 0.488, p < 0.001, and std. J-T static = 3.265, p = 0.001, respectively). This study provides prevalence estimates of RBD and its possible prodromal conditions based on a structured telephone interview and RWA measurement on PSG from the general population.

Striatal Subregion Analysis Associated with REM Sleep Behavior Disorder in Parkinson's Disease.

REM sleep behavior disorder (RBD) in Parkinson's disease (PD) is associated with characteristic clinical subtypes and prognosis. In addition, nigrostriatal pathway, the most vulnerable anatomical area in PD, formed neuronal network interplaying with cortical and subcortical structures, and which may cause PD clinical phenotype. We evaluated the regional selectivity of presynaptic striatal dopaminergic denervation associated with RBD in PD. We compared two groups (n = 16) of PD patients with and without RBD in terms of specific binding ratios (SBR) in subregions of the striatum, which were measured using positron emission tomography with 18F-FP-CIT. SBRs of the anterior and posterior caudate, ventral striatum, and posterior and ventral putamen regions were measured in more or less affected side, and right or left side, or bilateral sum of the striatum. Age, disease duration, and severity of parkinsonism were not significantly different between groups. Although group differences in all areas were not significant with multiple comparison corrections, SBR of the ventral striatum and anterior caudate in sum of both sides was significantly less in the RBD than in the non-RBD group without correction (p < 0.05). In the right anterior caudate and left ventral striatum, SBR was also lower in the RBD than in the non-RBD group without correction (p < 0.05). Attention function was impaired in the RBD group compared with the non-RBD group (p < 0.05). However, these statistical significances were not definite after correction of multiple comparisons (p > 0.05). There is a possibility that RBD in early PD may be associated with presynaptic dopaminergic denervation in the ventral striatum and anterior caudate, which may explain decreased attention in our RBD group. RBD in PD may imply a distinct pathological progression. However, further study using large numbers of participants or longitudinal observation is necessary for the statistical conclusion because of small sample size.

Blood neuroexosomal excitatory amino acid transporter-2 is associated with cognitive decline in Parkinson's disease with RBD.

BackgroundRapid eye movement (REM) sleep behavior disorder (RBD) predicts cognitive decline in Parkinson’s disease (PD) patients without dementia. However, underlying mechanisms remain unknown. Accumulating studies suggest glutamatergic system dysregulation is associated.ObjectiveTo examine the effect of RBD on the rate of cognitive decline in PD patients and investigate whether plasma levels of the neuroexosomal vesicular glutamate transporter-1 (VGLUT-1) and excitatory amino acid transporter-2 (EAAT-2) are altered in PD patients with RBD.MethodsThis study included 157 newly diagnosed cognitive normal PD patients and 70 healthy controls (HCs). Based on one-night polysomnography recordings, the PD subjects were divided into PD with and without RBD (PD-RBD and PD-nRBD) groups. All participants received a complete clinical and neuropsychological evaluation at baseline. Plasma levels of neuroexosomal VGLUT-1 and EAAT-2 were measured by ELISA kits. After a 3-year follow-up, we evaluated baseline plasma levels of neuroexosomal glutamate transporters in each group as a predictor of cognitive decline using MoCA score changes over 3 years in regression models.ResultsPlasma levels of neuron-derived exosomal EAAT-2 and VGLUT-1 were significantly lower in PD patients than in HCs. Plasma levels of neuroexosomal EAAT-2 were significantly lower in PD-RBD than PD-nRBD group at baseline. At the 3-year follow-up, PD-RBD patients presented greater cognitive decline. Lower baseline blood neuroexosomal EAAT-2 predicted cognitive decline over 3 years in PD-RBD patients (β = 0.064, P = 0.003).ConclusionThese findings indicate that blood neuroexosomal EAAT-2 is associated with cognitive decline in PD with RBD.

REM sleep without atonia and vestibular-evoked myogenic potentials: clinical brainstem dysfunction in early-stage Parkinson's disease and isolated REM sleep behavior disorder

ObjectiveTo determine whether the onset of rapid eye movement (REM) sleep behavior disorder (RBD) is associated with changes in brainstem neuronal pathway dysfunction as reflected by vestibular-evoked myogenic potentials (VEMPs) and to evaluate associations between VEMPs and REM sleep without atonia (RSWA) in patients with early-stage Parkinson's disease (PD) and isolated RBD (iRBD). MethodsEighty-two early-stage PD patients, 40 iRBD patients, and 41 healthy control individuals underwent one-night video-polysomnography (vPSG) and VEMPs examination. We compared cervical (cVEMP), ocular (oVEMP), and masseter (mVEMP) VEMP parameters among PD with RBD (PD + RBD), PD without RBD (PD-RBD), iRBD, and control groups and analyzed correlations between VEMPs and RSWA in PD and iRBD groups. ResultsThe PD + RBD group showed delays in bilateral cVEMP (Lp13, Ln23, Rn23: all p < 0.05) and oVEMP (Ln10, Rn10, Rp15: all p < 0.05) peak latencies compared with the PD-RBD group. Total cVEMP scores were higher in the PD + RBD group than in the iRBD group (p = 0.033). In PD patients, phasic RSWA was correlated with total cVEMP scores (p = 0.003), and tonic RSWA was correlated with left oVEMP scores (p = 0.013). ConclusionsBrainstem neurophysiology as evidenced by altered VEMPs in patients with PD and iRBD could reflect disease evolvement. Moreover, VEMPs alterations may vary depending on the presence of RBD in PD patients. The associations between altered RSWA and VEMP parameters highlight the meaningfulness of detecting brainstem dysfunction in early-stage PD.

AI-Enabled Algorithm for Automatic Classification of Sleep Disorders Based on Single-Lead Electrocardiogram.

Healthy sleep is an essential physiological process for every individual to live a healthy life. Many sleep disorders both destroy the quality and decrease the duration of sleep. Thus, a convenient and accurate detection or classification method is important for screening and identifying sleep disorders. In this study, we proposed an AI-enabled algorithm for the automatic classification of sleep disorders based on a single-lead electrocardiogram (ECG). An AI-enabled algorithm—named a sleep disorder network (SDN)—was designed for automatic classification of four major sleep disorders, namely insomnia (INS), periodic leg movement (PLM), REM sleep behavior disorder (RBD), and nocturnal frontal-lobe epilepsy (NFE). The SDN was constructed using deep convolutional neural networks that can extract and analyze the complex and cyclic rhythm of sleep disorders that affect ECG patterns. The SDN consists of five layers, a 1D convolutional layer, and is optimized via dropout and batch normalization. The single-lead ECG signal was extracted from the 35 subjects with the control (CNT) and the four sleep disorder groups (seven subjects of each group) in the CAP Sleep Database. The ECG signal was pre-processed, segmented at 30 s intervals, and divided into the training, validation, and test sets consisting of 74,135, 18,534, and 23,168 segments, respectively. The constructed SDN was trained and evaluated using the CAP Sleep Database, which contains not only data on sleep disorders, but also data of the control group. The proposed SDN algorithm for the automatic classification of sleep disorders based on a single-lead ECG showed very high performances. We achieved F1 scores of 99.0%, 97.0%, 97.0%, 95.0%, and 98.0% for the CNT, INS, PLM, RBD, and NFE groups, respectively. We proposed an AI-enabled method for the automatic classification of sleep disorders based on a single-lead ECG signal. In addition, it represents the possibility of the sleep disorder classification using ECG only. The SDN can be a useful tool or an alternative screening method based on single-lead ECGs for sleep monitoring and screening.

Abnormalities of Resting-State Electroencephalographic Microstate in Rapid Eye Movement Sleep Behavior Disorder.

Objective: Rapid eye movement (REM) sleep behavior disorder (RBD) is a disease characterized by dream enacting behavior and is now commonly believed to be a harbinger to alpha-synucleinopathy diseases such as dementia with Lewy bodies, Parkinson's disease, and multiple system atrophy. The aim of this study was to explore the quasi-stable topological structure of the brain in RBD by analyzing resting-state electroencephalography (EEG) microstates.Methods: We enrolled 22 participants with RBD and 46 healthy controls (HCs) with age and gender-matched. After the resting-state EEG recordings were acquired, EEG microstate features were analyzed to assess the functional networks of all participants.Results: Significant differences in the brain topological structure and temporal characteristics of sub-second brain activity were identified between the RBD and HCs. The RBD group had a shorter average duration of microstate A and microstate D when compared with HCs, and microstate B contributed more, while microstate D contributed significantly less to the RBD group. Furthermore, the average duration and proportion of microstate D were negatively correlated with the RBD questionnaire Hong Kong (RBDQ-HK) score.Conclusion: The result of this study indicates that the microstate dynamics is disturbed in RBD, which might jeopardize the flexibility and adaptability of the brain. Microstates are potential biomarkers to explore the early electrophysiological abnormality of alpha-synucleinopathy diseases.

Patients with REM sleep behavior disorder have higher serum levels of allantoin

IntroductionRapid eye movement (REM) sleep behavior disorder (RBD) is associated with an increased risk of developing Parkinson's disease (PD). Low uric acid (UA) levels are associated with the risk of development and progression of PD. Allantoin is the major oxidation product of UA and is considered as a biomarker of oxidative stress. We aimed to compare serum levels of UA, allantoin, and allantoin/UA ratio in RBD patients with those in healthy controls, and to examine their associations with clinical severity. MethodsWe evaluated serum levels of UA, allantoin, and allantoin/UA ratio in 38 RBD patients (one female, mean age 66.8 (SD 6.3) years) and in 47 controls (four females, 66.8 (7.6) years). All RBD patients were assessed according to an examination protocol, which included structured interview, Montreal Cognitive Assessment (MoCA), Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and dopamine transporter single-photon emission computed tomography (DAT-SPECT). The lower putaminal binding ratio from both hemispheres was used for analysis. ResultsMean serum allantoin concentration and allantoin/UA ratio were significantly increased in the RBD group compared to controls (2.6 (1.8) vs. 1.4 (0.7) μmol/l, p = 0.0004, and 0.008 (0.004) vs. 0.004 (0.002), p < 0.0001, respectively). There were no significant differences in UA levels between the two groups. No significant associations between any biochemical parameter and RBD duration, putaminal binding ratio on DAT-SPECT, MDS-UPDRS, or MoCA score were found. ConclusionSerum allantoin and allantoin/UA ratio are increased in RBD patients in comparison to controls, which may reflect increased systemic oxidative stress in prodromal synucleinopathy.

Prefrontal network dysfunctions in rapid eye movement sleep behavior disorder

IntroductionResting-state functional connectivity magnetic resonance imaging (rsfcMRI) of rapid eye movement (REM) sleep behavior disorder (RBD) may provide an early biomarker of α-synucleinopathy. However, few rsfcMRI studies have examined cognitive networks. To elucidate brain network changes in RBD, we performed rsfcMRI in patients with polysomnography-confirmed RBD and healthy controls (HCs), with a sufficiently large sample size in each group. MethodsWe analyzed rsfcMRI data from 50 RBD patients and 70 age-matched HCs. Although RBD patients showed no motor signs, some exhibited autonomic and cognitive problems. Several resting-state functional networks were extracted by group independent component analysis from HCs, including the executive-control (ECN), default-mode (DMN), basal ganglia (BGN), and sensory-motor (SMN) networks. Functional connectivity (FC) was compared between groups using dual regression analysis. In the RBD group, correlation analysis was performed between FC and clinical/cognitive scales. ResultsPatients with RBD showed reduced striatal-prefrontal FC in ECN, consistent with executive dysfunctions. No abnormalities were found in DMN. In the motor networks, we identified reduced midbrain-pallidum FC in BGN and reduced motor and somatosensory cortex FC in SMN. ConclusionWe found abnormal ECN and normal DMN as a possible hallmark of cognitive dysfunctions in early α-synucleinopathies. We replicated abnormalities in BGN and SMN corresponding to subclinical movement disorder of RBD. RsfcMRI may provide an early biomarker of both cognitive and motor network dysfunctions of α-synucleinopathies.

The probable REM sleep behavior disorder negatively affects health-related quality of life in Parkinson's disease with bilateral subthalamic nucleus stimulation

ObjectiveThe aim of this study was to compare the short- and long-term outcomes of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients with and without probable REM sleep behavior disorder (RBD). MethodsWe retrospectively reviewed 127 patients who underwent bilateral STN-DBS for PD with probable RBD from September 2011 to November 2018. Motor performance, physical and mental health-related quality of life (HRQoL), cognitive function, and depressive severity were compared between with or without probable RBD at the baseline and at the 1-, 3- or 5-year follow-up. ResultsOne hundred three PD patients (55 with RBD; 48 without RBD) were evaluated at the baseline and at the 1-year follow-up and 33 (17 with RBD, 16 without RBD) of them were examined at the 5-year follow-up. Motor performances were significantly improved in the non-RBD group compared to the RBD group at the 1-year follow-up, and there was a trend toward a greater difference in the physical HRQoL compared with the 1-year follow-up. There were also marked improvements of axial symptom and physical HRQoL in the non-RBD group compared with the RBD group from baseline to 5 years after STN-DBS. ConclusionOur study showed that RBD negatively affected the short- and long-term outcomes on motor performances, especially axial symptom and HRQoL after STN-DBS in PD patients.

Impulse control disorders in Parkinson disease and RBD: A longitudinal study of severity.

ObjectiveTo describe the prevalence, natural history, and risk factors for impulse control behaviors (ICBs) among people with Parkinson disease (PD), those with REM sleep behavior disorder (RBD), and controls.MethodsParticipants with early PD (within 3.5 years of diagnosis), those with RBD, and controls were clinically phenotyped and screened for ICBs longitudinally (with the Questionnaire for Impulsivity in Parkinson's Disease). ICB-positive individuals were invited for a semistructured interview, repeated 1 year later. The severity of the ICB was assessed with the Parkinson's Impulse Control Scale. Multiple imputation and regression models were used to estimate ICB prevalence and associations.ResultsData from 921 cases of PD at baseline, 768 cases at 18 months, and 531 cases at 36 months were included, with 21% to 25% screening positive for ICBs at each visit. Interviews of ICB screen–positive individuals revealed that 10% met formal criteria for impulse control disorders (ICD), while 33% had subsyndromal ICD (ICB symptoms without reaching the formal diagnostic criteria for ICD). When these data were combined through the use of multiple imputation, the prevalence of PD-ICB was estimated at 19.1% (95% confidence interval 10.1–28.2). On follow-up, 24% of cases of subsyndromal ICD had developed full symptoms of an ICD. PD-ICD was associated with dopamine agonist use, motor complications, and apathy but not PD-RBD. ICD prevalence in the RBD group (1%) was similar to that in controls (0.7%).ConclusionsICBs occur in 19.1% of patients with early PD, many persisting or worsening over time. RBD is not associated with increased ICD risk. Psychosocial drivers, including mood and support networks, affect severity.

Assessment of Amyloid Deposition in Patients With Probable REM Sleep Behavior Disorder as a Prodromal Symptom of Dementia With Lewy Bodies Using PiB-PET.

Introduction: Dementia with Lewy bodies (DLB) often exhibits REM sleep behavior disorder (RBD) at its prodromal stage. Meanwhile, DLB is often comorbid with Alzheimer's disease (AD)-type pathology. In typical AD, amyloid-β deposition begins considerably before the onset of dementia and has already reached a plateau at the stage of mild cognitive impairment. However, it is not known when amyloid accumulation starts in DLB with AD-type pathology. In the present study, we examined amyloid deposition in patients with RBD as a prodromal symptom of DLB using [11C]-Pittsburgh compound B positron emission tomography (PiB-PET).Methods: The subjects were 12 patients with probable RBD as diagnosed by the Japanese RBD screening questionnaire. They also showed abnormality in 123I-metaiodobenzylguanidine myocardial scintigraphy, a biomarker for DLB. For comparison, 11 patients with probable DLB were included. Applying PMOD software to the PiB-PET images, the global cortical distribution volume ratio was calculated and a ratio >1.3 was regarded as PiB-positive.Results: Two of the RBD patients (16.7%) and eight of the DLB patients (72.7%) were PiB-positive. The amyloid-positive rate was significantly lower in the RBD group than in the DLB group (P = 0.012).Conclusion: The prevalence of amyloid deposition in RBD as a prodromal symptom of DLB was significantly lower than that in DLB, suggesting that amyloid accumulation does not always begin at the early stage of DLB.

Heart rate variability in Parkinson disease and idiopathic REM sleep behavior disorder.

Heart rate variability, a marker of autonomic function modulation, is known to be blunted in Parkinson disease, although data remains conflicting and a putative modifying role of REM sleep behavior disorder persists unclarified. We assessed ten patients with idiopathic REM sleep behavior disorder patients, 18 patients with Parkinson disease and REM behavior disorder and eight patients with Parkinson disease without REM sleep behavior disorder. Heart rate variability analysis was performed in 5-min epochs selected from wake, Non-REM and REM polysomnography records. We compared heart rate variability measures by stage between two sets of groups: Parkinson disease vs. idiopathic RBD and patients with vs. without RBD, by using repeated measures ANOVA. There were no heart rate variability differences between Parkinson disease and idiopathic REM sleep behavior disorder groups. There were significant stage vs. group interactions (p = 0.045) regarding the high frequencies components when comparing patients with and without REM sleep behavior disorder, with the former presenting lower values and attenuation of sleep stage variations. Our study suggests that RBD is related with reduction in parasympathetic modulation of heart rate variability and blunting of sleep stage related variations.

Deterioration of executive dysfunction in elderly with REM sleep behavior disorder (RBD).

REM sleep behavior disorder (RBD) represents a major and relatively specific prodromal marker for synucleinopathies such as Parkinson's disease (PD), dementia with Lewy bodies, and multisystem atrophy. Because PD patients primarily suffer from executive dysfunction, we hypothesized that individuals with RBD show an impairment in the nonamnestic executive domain rather than in amnestic domains. To address this question, we investigated a cohort of 1145 healthy elderly (183 with RBD) cross-sectionally and a subgroup of 544 of them longitudinally (144 with RBD) over 6years. Assessments included the RBD screening questionnaire, the extended Consortium to Establish a Registry for Alzheimer's Disease test battery, and genetic testing for the risk variant rs356219 in the alpha-synuclein gene. In the cross-sectional analysis, the RBD subgroup showed worse performance in the Trail Making Test (TMT) part B and the delta-TMT_B-A when compared to non-RBD subjects. Longitudinal observation revealed a deterioration of TMT-B and delta-TMT_B-A in RBD subjects, a phenomenon that was not observed in the group of non-RBD subjects. These data argue for an early and progressive deterioration of executive dysfunction associated with RBD. Of the total cohort, 18 developed Parkinsonism including 16 with sporadic PD after a mean follow-up of 4.6years. Of the sporadic PD cases, 4.4% were from the probable RBD group and 0.8% of the non-RBD group. The potential of this dynamic for the detection of prodromal synucleinopathies seems relevant, but has to be determined in studies including converters.

Association of rapid eye movement sleep behavior disorder with sleep-disordered breathing in Parkinson's disease

ObjectiveRapid eye movement (REM) sleep behavior disorder (RBD) and sleep-disordered breathing (SDB) are two major sleep disturbances observed in patients with Parkinson's disease (PD). However, prior studies exploring the clinical correlations between RBD and SDB in PD have been limited. We aimed to investigate the relationship between RBD and SDB in PD using a case–control study. MethodsA total of 46 PD patients with Hoehn–Yahr stages ranging from 1 to 3 participated in the present study. Participants underwent polysomnography to diagnose the presence of RBD and SDB, and were classified into groups, accordingly. SDB was defined as an apnea–hypopnea index greater than 5. Comparison of clinical and sleep-respiratory parameters was performed among them. ResultsSDB was more frequent in the RBD group than in the non-RBD group (51.4% vs 9.1%, p = 0.016). PD patients with RBD had significantly reduced mean SaO2 and more severe sleep apnea–related parameters during total sleep and non-REM sleep in comparison with non-RBD PD patients. However, there were no differences on the REM-related apnea/hypopnea variables between participants with and without RBD (p > 0.05). Both the frequency of RBD and RBD screening questionnaire (RBDSQ) scores were higher in the participants with SDB than in the participants without SDB (p < 0.05). Furthermore, a significant negative correlation was found between RBDSQ and mean SaO2 in all participants. ConclusionsIn PD patients, SDB is more frequent and more severe in patients with RBD than in patients without, and RBD increases the risk of hypoxemia during sleep.

TCM psychological pathomechanism of RBD

Introduction: Resting-state functional MRI (rs-fMRI) has been shown by our group as a promising tool for the diagnosis of early Parkinson’s disease (PD). As REM sleep behavior disorder (RBD) is strongly associated with alpha-synucleinopathy, we aimed to investigate potential resting-state connectivity and structural changes in this promising prodromal group. Materials and methods: Twenty-six patients with polysomnography-proven idiopathic RBD and 22 age and sexmatched healthy controls were recruited from the Oxford Parkinson’s Disease Centre (OPDC) patient cohort. All subjects underwent a structural MRI protocol, including T1weighted and diffusion imaging. Blood-oxygen level dependent (BOLD) sequences were acquired during resting conditions, with the subject awake and their eyes open. Resting-state analysis was performed using probabilistic independent component analysis (ICA) as implemented in the Multivariate Exploratory Linear Optimized Decomposition into Independent Component FSL tool (MELODIC). A previously developed template of resting-sate networks typical for healthy elderly participants was used. Based on a priori hypotheses, three networks of interest (the basal ganglia network (BGN), the sensorimotor network (SMN) and the default mode network (DMN)), and one control network (the primary visual network (PVN)) were chosen for further analyses. The dual regression approach was then used to identify individual temporal dynamics and the associated spatial maps. Statistical comparisons between RBD and healthy controls were performed using permutation-based non-parametric inference. Results were corrected for age, sex and voxelwise gray matter volume, and defined as significant at p < 0.05 after FWE correction. Results: One of the RBD patients had significant cortical atrophy on their T1-weighted structural scan, and was excluded from further analyses. Patients with RBD performed marginally worse on the UPDRS part III (0.7 (1.1) vs. 3.0 (3.4), p = 0.005) and had lower cognitive scores (MMSE 29.3 (1.0) vs. 27.4 (1.7), p < 0.001). The two groups performed comparatively on the Purdue Pegboard Test (p = 0.5). At the time of the MRI investigation, none of the subjects fulfilled the UK Parkinson’s Disease Society Brain bank criteria for the diagnosis of idiopathic Parkinson’s disease and there was no clinical suspicion of any other neurological condition. There were no significant volumetric differences between patients with RBD and healthy controls. Voxel-based morphometry analysis did not yield any significant graymatter differences between the two groups. Similarly, no significant differences of fractional anisotropy were found using white matter tract analysis. Rs-fMRI revealed decreased coactivation within the BGN (involving the caudate, putamen, globus pallidus and the dorsolateral prefrontal cortex) and the SMN (precentral gyrus) of patients with RBD. No increased coactivation within these networks was seen in the RBD group, and no between-group differences were seen in the DMN and PVN. Conclusion: Rs-fMRI demonstrates significantly reduced coactivation within the BGN and SMN of patients with RBD. These results are similar to those found in early PD and are likely to represent pre-clinical basal ganglia dysfunction. This approach shows great promise as a potential biomarker for prodromal alpha-synucleinopathy. Acknowledgements: This studywas funded by theMonument Trust Discovery Award from Parkinson’s UK and supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. The authors report no conflict of interest in relation to this work.

Antidepressants Increase REM Sleep Muscle Tone in Patients with and without REM Sleep Behavior Disorder.

REM sleep behavior disorder (RBD) is associated with antidepressant treatment, especially in younger patients; but quantitative REM sleep without atonia (RSWA) analyses of psychiatric RBD patients remain limited. We analyzed RSWA in adults receiving antidepressants, with and without RBD. We comparatively analyzed visual, manual, and automated RSWA between RBD and control groups. RSWA metrics were compared between groups, and regression was used to explore associations with clinical variables. Tertiary-care sleep center. Participants included traditional RBD without antidepressant treatment (n = 30, 15 Parkinson disease [PD-RBD] and 15 idiopathic); psychiatric RBD receiving antidepressants (n = 30); and adults without RBD, including antidepressant-treated psychiatric (n = 30), untreated psychiatric (n = 15), and OSA (n = 60) controls. N/A. RSWA was highest in traditional and psychiatric RBD, intermediate in treated psychiatric controls, and lowest in untreated psychiatric and OSA controls (P < 0.01). RSWA distribution and type also differed between antidepressant-treated patients having higher values in anterior tibialis, and PD-RBD with higher submentalis and tonic RSWA. Psychiatric RBD had significantly younger age at onset than traditional RBD patients (P < 0.01). Antidepressant treatment was associated with elevated REM sleep without atonia (RSWA) even without REM sleep behavior disorder (RBD), suggesting that antidepressants, not depression, promote RSWA. Differences in RSWA distribution and type were also seen, with higher anterior tibialis RSWA in antidepressant-treated patients and higher tonic RSWA in Parkinson disease-RBD patients, which could aid distinction between RBD subtypes. These findings suggest that antidepressants may mediate different RSWA mechanisms or, alternatively, that RSWA type and distribution evolve during progressive neurodegeneration. Further prospective RSWA analyses are necessary to clarify the relationships between antidepressant treatment, psychiatric disease, and RBD.

Reduced striatal dopamine transmission in REM sleep behavior disorder comorbid with depression.

To investigate dopamine transmission in patients with comorbid REM sleep behavior disorder (RBD) and major depressive disorder (MDD). This is a case-control study including 11 medicated patients with comorbid RBD and MDD (mean age 47.5 ± 8.2), 8 medicated patients with MDD only (mean age 47.9 ± 8.4), and 10 healthy participants (mean age 46.5 ± 10.6 years). They underwent clinical assessment, video-polysomnography, olfactory tests, and neuroimaging studies ((18)F-DOPA, (11)C-raclopride, and (18)F-FDG PET neuroimaging). Compared with the 2 control groups, patients with comorbid RBD and MDD had significantly lower (18)F-DOPA uptake at 60 minutes in the putamen and caudate after controlling for age and sex effect (p < 0.05). There were no significant differences for the (11)C-raclopride and (18)F-FDG-PET. The (18)F-DOPA uptake in putamens had significant inverse correlation with severity of RBD symptoms (p < 0.01) and REM-related tonic muscle activity (p < 0.01). The comorbid RBD and MDD group had more impairment in olfactory function. Patients with comorbid RBD and MDD had presynaptic dopamine dysfunction and impaired olfactory function. There is a distinct possibility that the development of RBD symptoms among patients with MDD may represent an early phase of α-synucleinopathy neurodegeneration instead of a merely antidepressant-induced condition.

Frequency of REM sleep behavior disorders in patients with Parkinson's disease.

Sleep is prompted by natural cycles of activity in the brain and consists of two basic states: rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. REM sleep behavior disorder (RBD) is characterized by violent motor and vocal behavior during REM sleep which represents dream enactment. The normal loss of muscle tone, with the exception of respiratory, sphincter, extra ocular and middle ear muscles, is absent in patients with RBD. The origin of RBD is frequently unknown, but can be associated with degenerative neurological disorders, such as Parkinson's disease (PD). PD patients do not necessarily express features of RBD, which is identified in approximately third to a half of them. The aim of this study was to estimate the prevalence of RBD in a cohort of PD patients, as well as to identify risk-factors for its development. In the period from December 2010 to September 2011 we recruited 97 consecutive PD outpatients, treated in the Institute of Neurology, Clinical Center of Serbia, Belgrade. After establishing the diagnosis, all the patients filled out a specially constructed questionnaire with the following items: actual age, sex, age at disease onset, disease duration, form of the disease, type of treatment, duration of treatment, the presence of constipation, lessening of smell sense, and family history of PD. At entring the study, patients disability was scored using the Unified Parkinson's Disease Rating Scale (motor part - UPDRS). Cognitive abilities were assessed by the Mini Mental Status Examination (MMSE) scale, and depression symptoms by the 21-item Hamilton Depression Rating Scale (HDRS). The patients with PD were dichotomized to those with and without RBD using the RBD Questionnaire-Hong Kong (RBDQ-HK) in the manner of an interview. Forms of PD, mode of treatment, sex, constipation and family history were investigated using the Fishers χ2 test. Symptoms and treatment duration, the presence of smell disturbances, MMSE score, UPDRS motor score and HDRS score were analyzed by implementation of the Z-test. Actual age and age at disease onset were evaluated by the unpaired t-test. The RBD-positive group contained 15 (15.5%) patients, while in the rest of them (82/97), RBD was not identified (nonRBD group). There was no difference between the two groups considering gender distribution (p = 0.847), age (p = 0.577), age at disease onset (p = 0.141 ), duration. of PD (p = 0.069), family history (p = 0.591), type of initial symptoms (p = 0.899), constipation (p = 0.353), olfaction (p = 0.32) and MMSE scores (p = 0.217). The duration of treatment in the RBD group was longer than in the non-RBD group (9.4 ± 5.3 and 6.3 ± 3.9 years, respectively; p = 0.029), and the UPDRS motor score in the RBD group was higher (19.1 ± 9.4 and 12.7 ± 8.2, respectively; p = 0.013). Also, HDRS scores were higher in patients expressing RBD (10.1 ± 6.0 and 6.4 ± 4.5, respectively; p = 0.019). We found that 15.5% of the consecutive PD patients had RBD, and that the patients with RBD differed from the non-RBD ones regarding duration of treatment, disease and depressive symptoms severity.

Polysomnography Findings of Rapid Eye Movement Sleep Behavior Disorder in Korean Young Age Population

Objectives: Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia manifested by vivid dreams associated with complex motor behavior during REM sleep. It was originally described as a parasomnia in older men, however it is now recognized as a disorder of all ages and both sexes. We determine clinical characteristics of young age RBD patients who visited single sleep center in Korea. Methods: This is a retrospective chart review of RBD patients visiting single sleep center from August, 2003 to August, 2014. Patients with history of RBD were evaluated with overnight polysomnography (PSG). The PSG re sults were compared between young (<40 years old) and elderly (40 years or older). Results: The total of 149 patients (young RBD: n=22, 14.8%, elderly RBD: n=127, 85.2%) were included. Mean age upon diagnosis were 24.97±7.42 years (male: n=17, 77.3%) for young age RBD, and 64.40±8.73 years (male: n=82, 64.6%) for elderly RBD patients. PSG results reveled young age RBD patients had longer total sleep time (416.16±44.19, 345.73±78.03, p<0.001), higher sleep efficiency (87.60 ±6.90, 76.85±14.07, p<0.001), less arousal index (17.85±20.81, 23.14±12.15, p<0.001). Three patients in young age RBD group were also diag nosed with narcolepsy. Conclusions: This is the first study to evaluate PSG findings in young age RBD in Korean. The young age RBD sleep longer and better, with less arousal. Further on they have associated with sleep talking and walking, and narcolepsy. While few previous reports indicated association with medication use, our young age population was not related to medication effects. J Korean Sleep Res Soc 2014;11(2):57-60

REM sleep behavior disorder: association with motor complications and impulse control disorders in Parkinson's disease.

Clinical phenotypes such as old age, longer disease duration, motor disability, akineto-rigid type, dementia and hallucinations are known to be associated with REM sleep behavior disorder (RBD) in Parkinson's disease (PD). However, the relationship between motor fluctuations/impulse control and related behaviors (ICRB) and RBD is not clear. We designed this study to elucidate the clinical manifestations associated with RBD to determine the implications of RBD in PD. In a cross-sectional study, a total of 994 patients with PD were interviewed to determine the presence of RBD and their associated clinical features including motor complications and ICRB. Of the 944 patients, 578 (61.2%) had clinical RBD. When comparing the clinical features between patients with RBD (RBD group) and without RBD (non-RBD group), older age, longer disease duration, higher Hoehn and Yahr stage (H&Y stage), higher levodopa equivalent daily dose (LEDD), and the existence of wearing off, dyskinesia, freezing, and ICRB, especially punding, were associated with the RBD group compared to the non-RBD group (P<.05 in all). Multivariate analysis showed that motor complications including wearing off, peak dose dyskinesia, and diphasic dyskinesia were the only relevant factors for RBD after adjusting for age and disease duration. Motor complications and ICRB are more frequent in patients with RBD than in patients without RBD. In addition, motor complications are related to RBD even after adjusting for age and disease duration.