Idiopathic Rapid Eye Movement Research Articles

CD4+ T-cell Transcription Factors in Idiopathic REM Sleep Behavior Disorder and Parkinson's Disease.

CD4+ T-cell dysregulation occurs in Parkinson's disease (PD); however, it is unknown whether it contributes to PD development. The objective of this study was to investigate transcription factor gene expression in CD4+ T cells in idiopathic rapid eye movement sleep behavior disorder, the strongest risk factor for prodromal PD. Expression of transcription factors (TBX21, STAT1, STAT3, STAT4, STAT6, RORC, GATA3, FOXP3, and NR4A2) was measured in CD4+ T cells from 33 polysomnographically confirmed idiopathic rapid eye movement sleep behavior disorder subjects and compared with expression in cells from matched healthy subjects and antiparkinson drugs-naive PD patients. Compared with healthy subjects, idiopathic rapid eye movement sleep behavior disorder subjects and PD patients had lower TBX21, STAT3, and STAT4, and higher FOXP3 expression. TBX21 expression discriminated healthy subjects from idiopathic rapid eye movement sleep behavior disorder subjects and PD patients, but not idiopathic rapid eye movement sleep behavior disorder subjects with PD. In idiopathic rapid eye movement sleep behavior disorder subjects CD4+ T cells exhibit a peculiar molecular signature strongly resembling cells from PD patients, suggesting early involvement of peripheral immunity in PD. © 2020 International Parkinson and Movement Disorder Society.

Altered structure and functional connectivity of the central autonomic network in idiopathic rapid eye movement sleep behaviour disorder.

Evidence suggests peripheral autonomic structures may contribute to autonomic dysfunction in idiopathic rapid eye movement sleep behaviour disorder (iRBD). However, whether the central autonomic network (CAN) is affected in iRBD remains unclear. Magnetic resonance imaging data were acquired from 65 participants (32 patients with iRBD and 33 matched healthy controls). We investigated the CAN in patients with iRBD using a combined voxel-based morphometry and resting-state functional connectivity analysis and characterised the relationships between alterations of the CAN and autonomic symptoms. Patients with iRBD had significantly reduced grey matter volume in the brainstem, anterior cingulate and insula compared with healthy controls. Functional connectivity analysis revealed reduced functional connectivity between the brainstem and the cerebellum posterior lobe, temporal lobe and anterior cingulate in patients with iRBD. In patients with iRBD, both reduced grey matter volume and decreased functional connectivity of the CAN were negatively correlated with the Scales for Outcomes in Parkinson's Disease-Autonomic scores. The present study demonstrated that both the structure and the functional connectivity of the CAN were abnormal in patients with iRBD. In addition, correlation analysis suggested that CAN abnormalities may also play a role in the development of autonomic symptoms in iRBD.

Structural and functional brain alterations in patients with idiopathic rapid eye movement sleep behavior disorder

ObjectiveTo investigate structural and functional alterations in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) compared with healthy controls. MethodsTwenty-seven patients with polysomnography-confirmed iRBD and 33 healthy subjects were recruited. All subjects underwent a 3-tesla structural and resting-state functional magnetic resonance imaging (fMRI) examination. Voxel-based morphometry (VBM) analysis was performed to assess grey matter alterations between groups. The amplitude of low-frequency fluctuations (ALFF) was calculated and then compared to measure differences in spontaneous brain activity. Correlations were performed to explore associations between imaging metrics and clinical characteristics in iRBD patients. ResultsCompared with healthy controls, patients with iRBD had decreased grey matter volume in the frontal, temporal, parietal, occipital cortices as well as increased grey matter volume in cerebellum posterior lobe, putamen, and thalamus. Patients with iRBD also exhibited increased ALFF values in the right parahippocampal gyrus. Olfaction correlated with ALFF value changes in occipital cortices. ConclusionsPatients with iRBD had widespread decreases of grey matter volume. Increases of grey matter volume in cerebellum, putamen, and thalamus may suggest a compensatory effect, while the altered ALFF values in parahippocampal gyrus and occipital cortices may play a role in the underlying process of neurodegeneration in this disorder.

Metformin as a Potential Neuroprotective Agent in Prodromal Parkinson's Disease-Viewpoint.

To date, there are no clinically effective neuroprotective or disease-modifying treatments that can halt Parkinson's disease (PD) progression. The current clinical approach focuses on symptomatic management. This failure may relate to the complex neurobiology underpinning the development of PD and the absence of true translational animal models. In addition, clinical diagnosis of PD relies on presentation of motor symptoms which occur when the neuropathology is already established. These multiple factors could contribute to the unsuccessful development of neuroprotective treatments for PD. Prodromal symptoms develop years prior to formal diagnosis and may provide an excellent tool for early diagnosis and better trial design. Patients with idiopathic rapid eye movement behavior disorder (iRBD) have the highest risk of developing PD and could represent an excellent group to include in neuroprotective trials for PD. In addition, repurposing drugs with excellent safety profiles is an appealing strategy to accelerate drug discovery. The anti-diabetic drug metformin has been shown to target diverse cellular pathways implicated in PD progression. Multiple studies have, additionally, observed the benefits of metformin to counteract other age-related diseases. The purpose of this viewpoint is to discuss metformin's neuroprotective potential by outlining relevant mechanisms of action and the selection of iRBD patients for future clinical trials in PD.

The Neural Signature of Impaired Dual-Tasking in Idiopathic Rapid Eye Movement Sleep Behavior Disorder Patients.

The objective of this cross-sectional study was to determine the neural signature of dual-tasking deficits in idiopathic rapid eye movement sleep behavior disorder using a validated gait paradigm. Fifty-eight participants (28 controls; 30 idiopathic rapid eye movement sleep behavior disorder patients) were recruited; 52 participants had functional MRI scans as they performed a validated dual-task virtual reality gait paradigm using foot pedals. Forty-one participants completed single- and dual-task "overground walking" on a pressure sensor carpet. Idiopathic rapid eye movement sleep behavior disorder patients showed deficits in dual-tasking (i.e., greater mean step time) compared to controls during "overground walking." Functional MRI revealed that idiopathic rapid eye movement sleep behavior disorder patients had reduced blood-oxygen-level-dependent signal change in the dorsal caudate nucleus, and significantly different corticostriatal functional connectivity patterns from controls, when dual-tasking in high versus low cognitive load. While controls showed greater connectivity between frontoparietal and motor networks, idiopathic rapid eye movement sleep behavior disorder patients exhibited less change in this connectivity as a function of cognitive load. These findings demonstrate evidence of dual-task gait deficits in idiopathic rapid eye movement sleep behavior disorder patients, underpinned by disrupted corticostriatal connectivity. Minimal differences in the level of functional connectivity between dual-tasking conditions of high and low cognitive load suggest that idiopathic rapid eye movement sleep behavior disorder patients recruit cognitive networks to control gait even when the cognitive demands are low. This may indicate a compensatory strategy for early cognitive decline in idiopathic rapid eye movement sleep behavior disorder. © 2020 International Parkinson and Movement Disorder Society.

Severity of idiopathic rapid eye movement sleep behavior disorder correlates with depression and alexithymia

BackgroundDepression and alexithymia often accompany early stages of Parkinson's disease (PD). However, these symptoms in idiopathic rapid eye movement sleep behavior disorder (iRBD) remain incompletely understood. The aim of this study was to compare depression and alexithymia between iRBD patients and healthy controls, and to evaluate the association between clinical RBD severity and severity of depression and alexithymia. MethodsPolysomnography-confirmed iRBD patients (n = 86) and healthy controls (n = 74) were enrolled. Clinical RBD severity was assessed using the RBD questionnaire-Hong Kong (RBDQ-HK). Depression and alexithymia were evaluated by the Beck Depression Inventory (BDI) and the 20-item Toronto Alexithymia Scale (TAS-20), respectively. Multivariate linear regression analysis was performed with adjustments for several covariates to determine the correlations between RBD severity and severity of depression and alexithymia. ResultsBDI scores were significantly higher in the iRBD group (10.6 ± 7.3) than in healthy controls (8.2 ± 6.0, p = 0.024). Higher total RBDQ-HK scores were associated with more severe depression in iRBD patients, even after controlling for confounding variables. iRBD patients exhibited significantly higher TAS-20 scores (45.7 ± 10.4) than healthy controls (42.1 ± 9.8, p = 0.026). Total RBDQ-HK scores were positively correlated with TAS-20 scores independent of BDI scores. ConclusionsPatients with iRBD were more depressed and had more severe alexithymia than healthy controls. Notably, as the clinical severity of RBD increased, both depression and alexithymia worsened.

Changes in Regional Cerebral Perfusion Over Time in Idiopathic REM Sleep Behavior Disorder.

Idiopathic rapid eye movement sleep behavior disorder is associated with increased risk of neurodegeneration, but the temporal evolution of regional perfusion, a marker of cerebral activity, has not been characterized. The objective of the current study was to study longitudinal regional perfusion in patients with idiopathic rapid eye movement sleep behavior disorder. Thirty-seven patients and 23 controls underwent high-resolution single-photon emission computed tomography. After 17 months on average, scans were repeated for idiopathic rapid eye movement sleep behavior disorder patients. We compared regional cerebral blood flow between groups and over time. At baseline, patients showed lower relative regional perfusion in the anterior frontal and lateral parietotemporal cortex compared with controls. However, over time, patients showed an increase in relative regional perfusion in the anterior frontal, lateral parietal, and occipitotemporal cortex, reverting toward normal control levels. Patients with idiopathic rapid eye movement sleep behavior disorder showed significant areas of relative regional hypoperfusion, which disappeared over time to finally return to average levels, suggesting possible developing compensation in areas affected by neurodegeneration. © 2020 International Parkinson and Movement Disorder Society.

A longitudinal study on α-synuclein in plasma neuronal exosomes as a biomarker for Parkinson's disease development and progression.

The identification of reliable diagnostic and prognostic biomarkers for Parkinson's disease (PD) is urgently needed. Here, we explored the potential use of α-synuclein (α-syn) in plasma neuronal exosomes as a biomarker for early PD diagnosis and disease progression. This study included both cross-sectional and longitudinal designs. The subjects included 36 patients with early-stage PD, 17 patients with advanced PD, 20 patients with idiopathic rapid eye movement sleep behavior disorder and 21 healthy controls (HCs). α-syn levels were measured by electrochemiluminescence immunoassay. A subgroup of patients with early-stage PD (n=18) participated in a follow-up examination with repeated blood collection and clinical assessments after an average of 22months. The α-syn levels in plasma neuronal exosomes were significantly higher in patients with early-stage PD compared with HCs (P=0.007). Differences in α-syn levels between patients with idiopathic rapid eye movement sleep behavior disorder and HCs did not reach statistical significance (P=0.08). In addition, Spearman correlation analysis revealed that neuronal exosomal α-syn concentrations were correlated with Movement Disorders Society Unified Parkinson's Disease Rating Scale III/(I+II+III) scores, Non-Motor Symptom Questionnaire scores and Sniffin' Sticks 16-item test scores of patients with PD (P<0.05). After a mean follow-up of 22months in patients with early-stage PD, a Cox regression analysis adjusted for age and gender showed that longitudinally increased α-syn rather than baseline α-syn levels were associated with higher risk for motor symptom progression in PD (P=0.039). Our results suggested that α-syn in plasma neuronal exosomes may serve as a biomarker to aid early diagnosis of PD and also as a prognostic marker for PD progression.

Reduced dopamine transporter binding predicts early transition to Lewy body disease in Japanese patients with idiopathic rapid eye movement sleep behavior disorder

PurposeWe examined dopamine transporter (DAT) binding in Japanese patients with idiopathic rapid eye movement sleep behavior disorder (IRBD) as a biomarker for the development of Lewy body disease (LBD). Methods[123I]FP-CIT SPECT (DAT-SPECT) scans of 74 IRBD patients were compared to those from healthy Japanese subjects, and the predictive value for conversion to LBD during a 5-year follow-up was evaluated. ResultsBaseline DAT deficits (Z-score ≤ −2.5) were observed in 25 (33.8%) of the IRBD patients. During follow-up, 25 patients (33.8%) developed LBD [19 Parkinson's disease and 6 dementia with Lewy bodies], with a mean latency of 2.4 ± 1.6 years from imaging. The receiver operating characteristics curve revealed that the Z-score of baseline DAT binding in the striatum of abnormal DAT-SPECT patients who later developed LBD differed from those who remained disease-free. Kaplan-Meier survival analysis showed an increased risk of LBD in patients with a Z-score ≤ −2.5 for DAT binding in the striatum of abnormal DAT-SPECT patients compared to patients with a Z-score > −2.5. ConclusionsDAT-SPECT identifies IRBD patients at short-term risk for developing LBD. Decreased DAT binding in the striatum (Z-score ≤ −2.5) predicts development of LBD within 5 years, and may be useful in future disease-prevention trials in IRBD patients.

The fate of patients with REM sleep behavior disorder and mild cognitive impairment

ObjectiveTo investigate clinical and dopaminergic pre-synaptic brain imaging characteristics of subjects with idiopathic rapid eye movement (REM) behavior disorder (iRBD) and mild cognitive impairment (MCI), and to evaluate the combined predictive value of risk factors for short-term conversion to synucleinopathy. MethodIn sum, 44 polysomnography (PSG)-confirmed iRBD patients (68.5 ± 7.2 years; 38 males) underwent 123I-FP-CIT-SPECT, comprehensive neuropsychological evaluation, clinical examination and clinical follow-up every six months (30.6 ± 21.5 months). Step-wise logistic regression was applied to identify those features discriminating iRBD patients with (iRBD-MCI; n = 14) and without MCI (normal cognition [NC], iRBD-NC; n = 30). The risk of neurodegeneration was estimated with Kaplan–Meier analysis. Predictors of phenoconversion were assessed with Cox proportional-hazards analysis, adjusting for age, gender and education. A generalized linear model (GLM) was applied to define the best combination of risk factors predicting conversion at follow-up. ResultsAt baseline, patients with iRBD-MCI showed reduced striatal dopamine transporter (DAT) specific to non-displaceable binding ratio (SBR) and more constipation compared with iRBD-NC patients (p < 0.0001). During the follow-up, 10 patients (22.7%) develop an overt synucleinopathy. GLM analysis showed that patients with orthostatic hypotension, non-motor experiences of daily living, reduced putaminal DAT-SPECT SBR, and cognitive impairment in verbal memory/visuoconstruction abilities were at higher risk of phenoconversion (Hazard Ratio [HR] 26.05; Sensitivity 90%; Specificity 100%; Accuracy 97.73%; Positive Predictive Value 100%; Negative Predictive Value 97.14%). ConclusionsiRBD-MCI patients showed a more severe dopaminergic neuroimaging and clinical phenotype. Combining clinical and neuroimaging markers allowed to achieve excellent ability in identifying iRBD patients at high risk of developing a synucleinopathy within about three years from diagnosis.

Comparative study of the substantia nigra echogenicity and 123I-Ioflupane SPECT in patients with synucleinopathies with and without REM sleep behavior disorder

ObjectivesHyperechogenicity of the substantia nigra (SN) and abnormal dopamine transporter-single-photon emission computed tomography (DAT-SPECT) are biomarkers commonly used in the assessment of prodromal synucleinopathy. Our goals were as follows: (1) to compare echogenicity of SN in idiopathic rapid eye movement (REM) behavior disorder (iRBD), Parkinson's disease (PD) without RBD (PD-noRBD), PD with RBD (PD + RBD), and control subjects; and (2) to examine association between SN degeneration assessed by DAT-SPECT and SN echogenicity. Patients/methodsA total of 61 subjects with confirmed iRBD were examined using Movement Disorders Society-unified PD rating scale (MDS-UPDRS), TCS (transcranial sonography) and DAT-SPECT. The results were compared with 44 patients with PD (25% PD + RBD) and with 120 age-matched healthy subjects. Results and conclusionThe abnormal SN area was found in 75.5% PD, 23% iRBD and 7.3% controls. Median SN echogenicity area in PD (0.27 ± 0.22 cm2) was higher compared to iRBD (0.07 ± 0.07 cm2; p < 0.0001) and controls (0.05 ± 0.03 cm2; p < 0.0001). SN echogenicity in PD + RBD was not significantly different from PD-noRBD (0.30 vs. 0.22, p = 0.15).Abnormal DAT-SPECT was found in 16 iRBD (25.4%) and 44 PD subjects (100%). No correlation between the larger SN area and corresponding putaminal binding index was found in iRBD (r = −0.13, p = 0.29), nor in PD (r = −0.19, p = 0.22).The results of our study showed that: (1) SN echogenicity area in iRBD was higher compared to controls, but the hyperechogenicity was present only in a minority of iRBD patients; (2) SN echogenicity and DAT-SPECT binding index did not correlate in either group; and (3) SN echogenicity does not differ between PD with/without RBD.

Compromised Dynamic Cerebral Autoregulation in Patients With Idiopathic Rapid Eye Movement Behavior Disorder: A Case-Control Study Using Transcranial Doppler.

BackgroundPatients with idiopathic rapid eye movement behavior disorder (IRBD) have been suggested to exhibit altered cerebral perfusion and abnormal cerebral blood flow, which imply a possibility of cerebral autoregulation (CA) impairment. We aimed to investigate the dynamic CA (dCA) in patients with IRBD during wakefulness and to explore the correlations between dCA parameters and clinical measurements.MethodsWe assessed the dCA capability of 30 patients with IRBD and 36 sex- and age-matched healthy controls by using transcranial Doppler and finger plethysmography. CA function was evaluated by transfer function analysis based on spontaneous oscillation of cerebral blood flow and arterial blood pressure. Transfer function parameters (phase difference and gain) were used to quantify the CA.ResultsNo significant differences were observed between the right and left middle cerebral artery dCA parameters (phase difference and gain) of both groups. Patients with IRBD had significantly lower phase difference than the healthy controls, indicating their impaired CA capability. Besides, the value of gain in patients with IRBD was higher than the healthy controls, but the difference did not reach statistical level.ConclusionsCA function is compromised in patients with IRBD during wakefulness, which might be an intermediate link between IRBD and neurological symptoms.

Changes of brain structural network properties in patients with rapid eye movement sleep behavior disorder

To investigate the changes in behaviors and brain structural network in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD). Twenty patients with iRBD (iRBD group) and 22 healthy control subjects were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn-Yahr staging. Diffusion tensor imaging and graph- theoretical analysis were performed for analyzing the topological characteristics of brain structural networks of the patients, and the correlation between the behavioral changes and the changes in the topological characteristics of the brain networks was analyzed. The UPDRS score was significantly higher in iRBD group than in the healthy control group (P < 0.05). No significant difference was found in small-world attributes between the patients with iRBD and the control subjects (P>0.05). The patients with iRBD exhibited significantly shortened characteristic shortest path length Lp (P < 0.05) and significantly increased global efficiency, local efficiency and assortativity (P < 0.05). Examination of regional topological properties of the brain network revealed abnormal node properties in the frontal, temporal, parietal, occipital, and striatal and limbic lobes in patients with iRBD. The patients also had significantly increased degree centrality of the left pallidum and enhanced nodal efficiency in the left thalamus, superior temporal gyrus, temporal pole and bilateral superior occipital gyrus, bilateral putamens as well as the right gyrus rectus, amygdala, supramarginal gyrus, and middle temporal gyrus. The nodal local efficiency was significantly increased in the left superior frontal gyrus, middle cingulate gyrus, superior parietal gyrus, bilateral fusiform gyrus, right superior motor area, postcentral gyrus and angular gyrus of the patients with iRBD. The nodal shortest path was significantly shortened in the left superior motor area, pallidum, thalamus, superior temporal gyrus, temporal pole, bilateral putamens, bilateral superior occipital gyrus, right rectus gyrus, amygdala, supramarginal gyrus and middle temporal gyrus, and the nodal clustering coefficient was significantly lowered in the left superior occipital gyrus of the patients. In patients with iRBD, the UPDRS I score was positively correlated with the nodal efficiency in the right supramarginal gyrus (r=0.50, P < 0.05) and local nodal efficiency in the right fusiform gyrus (r=0.53, P < 0.05), and negatively correlated with the nodal clustering coefficient in the left superior occipital gyrus (r=-0.552, P < 0.05). Patients with iRBD present with abnormal changes in mental condition, behaviors, emotions, activities of daily living and motor functions. The brain structural network of patient with iRBD still has a small-world property with abnormal global topological property and abnormal distribution of local topological property in the cortex, striatum and limbic system.

Retrospective analysis of the incidence of neurodegenerative disorders in idiopathic rapid eye movement sleep behavior disorder: a preliminary study in Japanese patients.

Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is characterized by abnormal and potentially violent behaviors during REM sleep, typically observed in older adult subjects. Previous reports have described a high risk for neurodegeneration in patients with iRBD; however, to date, no published study has analyzed an adequate number of Japanese patients. We retrospectively analyzed the incidence of neurodegenerative disorders among patients diagnosed with iRBD in our department. The data were retrospectively collected from patients' medical records. The patients included in the study were diagnosed with iRBD using polysomnography in our department, from May 1, 2005 to November 30, 2018, with a follow-up of ≥6 months. Using the Kaplan-Meier (KM) method, we estimated the incidence of later diagnoses of neurodegenerative disorders among this cohort of patients with iRBD. Among 57 consecutive patients diagnosed with iRBD, 14 (24.6%) were later diagnosed with neurodegenerative disorders. Using the KM method, we estimated that the incidence was as high as 18.5% and 68.1% at 5 and 10 years, respectively. Of the 14 patients who developed neurodegenerative disorders, 12 (85.7%) had α-synucleinopathies (Parkinson's disease in eight patients, Lewy body dementia in three, Alzheimer's-type dementia in two, and multiple system atrophy in one). The results of this study suggest the high likelihood that iRBD may subsequently progress to neurodegenerative disorders in Japanese patients, a finding similar to those previously reported by studies performed overseas. Further studies using standardized prospective evaluation methods must be performed in Japan.

Predictors of Conversion to α-Synucleinopathy Diseases in Idiopathic Rapid Eye Movement Sleep Behavior Disorder.

Idiopathic rapid eye movement sleep behavior disorder (iRBD) often precedes the development of α-synucleinopathy diseases. We aimed to assess the predictive value of clinical variables and biomarkers for the early development of α-synucleinopathy diseases in subjects with iRBD. 56 patients with RBD Screening Questionnaire (RBDSQ) scores ≥5 at baseline and subsequent visit were enrolled as probable iRBD from the Parkinson's Progression Markers Initiative (PPMI) database. Baseline clinical data and biomarkers were analyzed. The endpoint was defined as disease progression to α-synucleinopathy diseases. Cox proportional hazard and Kaplan-Meier analyses were used to evaluate the predictive values of the indicators. During a mean follow-up duration of 5.1 years, 15 of 56 patients (26.8%) developed α-synucleinopathy diseases. Baseline clinical variables, including University of Pennsylvania Smell Identification Test (UPSIT, HR = 26.18, p = 0.004), 15-item Geriatric Depression Scale (GDS, HR = 14.26, p = 0.001), Montreal Cognitive Assessment (MoCA, HR = 3.56, p = 0.025), and Hopkins Verbal Learning Test Total recall (HVLT-TR, HR = 3.70, p = 0.014); genotype status of TMEM175 (HR = 3.74, p = 0.017), SCN3A (HR = 5.81, p = 0.022) and NUCKS1 (HR = 0.342, p = 0.049); ratio of phosphorylated tau to total tau (p-tau/t-tau, HR = 8.36, p = 0.001) in cerebrospinal fluid; and gray matter atrophy in inferior frontal gyrus (IFG, HR = 15.49, p = 0.001) were associated with phenoconversion to α-synucleinopathy diseases. A model combined the three independent variables (UPSIT, TMEM175 and gray matter atrophy in IFG) exhibited significantly improved predictive performance. For patients with iRBD, progression to α-synucleinopathy diseases can be predicted with good accuracy using a model combining clinical variables and biomarkers, which could form a basis for future disease prevention.

Comorbid neuropsychiatric and autonomic features in REM sleep behavior disorder

ObjectiveOur aim is to define the extent of comorbidities in order to improve clinical care of patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) utilizing the REM Sleep Behavior Disorder Associations with Parkinson's Disease Study (RAPiDS) cohort. MethodsConsecutive adult study participants with iRBD confirmed on polysomnogram (PSG) were prospectively recruited from the Weill Cornell Center for Sleep Medicine. Evaluations comprised multiple facets of sleep, neurological, autonomic, and psychiatric function. ResultsParticipants evaluated included 30 individuals with iRBD, with mean 1.5 ± 2.3 years from PSG to neuropsychiatric evaluation. Mean age was 59.5 ± 16.0 years at time of PSG, and 6/30 were women. Urinary difficulties were reported in 14/30 (47%): slight 7 (23%), mild 4 (13%), moderate 2 (7%), and severe 1 (3.0%). Ten out of 29 (34%) had abnormal Montreal Cognitive Assessment (MoCA) scores and the mean was 26.5 ± 3.2. The distribution of MoCA scores was significantly associated with urinary problems insofar as the more severe urinary problems were, the lower the MoCA scores (p = 0.04). ConclusionsIn this RAPiDS cohort, we detected an unexpectedly high occurrence of non-motor dysfunction. Our results point to the need for screening patients with iRBD for complaints that are actionable, for example those affecting mood, cognition, urinary function, and bowel function. We propose the term RBD+ to be used to identify such individuals. For the quality of life in patients diagnosed with RBD, a closer look by the clinician should be enacted, with appropriate referrals and workup.

Characterizing the heterogeneous metabolic progression in idiopathic REM sleep behavior disorder

ObjectiveIdiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of synucleinopathies such as Parkinson’s disease (PD). Positron emission tomography (PET) with 18F-FDG reveals metabolic perturbations, which are scored by spatial covariance analysis. However, the resultant pattern scores do not capture the spatially heterogeneous trajectories of metabolic changes between individual brain regions. Assuming metabolic progression occurs as a continuum from the healthy control (HC) condition to iRBD and then PD, we investigated spatial dynamics of progressively perturbed glucose metabolism in a cross-sectional study. Methods19 iRBD patients, 38 PD patients and 19 HC subjects underwent 18F-FDG PET. The images were spatially normalized, scaled to the global mean uptake, and automatically parcellated. We contrasted regional metabolism by group, and allocated the inferred progression to one of several possible trajectories. We further investigated the correlations between 18F-FDG uptake and the disease duration in the iRBD and PD groups, respectively. We also explored relationships between 18F-FDG uptake and the Unified Parkinson’s Disease Rating Scale motor (UPDRS III) scores in the PD group. ResultsPD patients exhibited more extensive relative hyper- and hypo-metabolism than iRBD patients. We identified three dynamic metabolic trajectories, cross-sectional hypo- or hypermetabolism, cross-sectionally unchanged hypo- or hypermetabolism, cross-sectionally late hypo- or hypermetabolism, appearing only in the contrast of PD with iRBD. No correlation was found between relative 18F-FDG metabolism and disease duration in the iRBD group. Regional hyper- and hypo-metabolism in the PD patients correlated with disease duration or clinical UPDRS III scores. ConclusionCerebral metabolism changes heterogeneously in a continuum extending from HC to iRBD and PD groups in this preliminary study. The distinctive metabolic trajectories point towards a potential neuroimaging biomarker for conversion of iRBD to frank PD, which should be amenable to advanced pattern recognition analysis in future longitudinal studies.

Cholinergic denervation in patients with idiopathic rapid eye movement sleep behaviour disorder.

Cholinergic dysfunction appears to play a role in the cognitive impairment observed in Parkinson's disease and dementia with Lewy bodies. The occurrence of cholinergic dysfunction in the early stages of these conditions, however, has not been investigated. The objective of this study was to investigate cholinergic function in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), a disorder recognized to be an early stage of both Parkinson's disease and dementia with Lewy bodies. A total of 21 patients with polysomnography-confirmed iRBD with no evidence of parkinsonism and cognitive impairment and 10 controls underwent positron emission tomography (PET) to assess brain acetylcholinesterase levels (11 C-donepezil PET) and nigrostriatal dopaminergic function (18 F-DOPA PET). Clinical examination included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination and Montreal Cognitive Assessment. The 11 C-donepezil PET was successfully performed in 17 patients with iRBD and nine controls. Compared with controls, patients with iRBD showed a mean 7.65% reduction in neocortical 11 C-donepezil levels (P=0.005). Bilateral superior temporal cortex, occipital cortex, cingulate cortex and dorsolateral prefrontal cortex showed the most significant reductions at voxel level. Reduced neocortical 11 C-donepezil binding in our patients indicates cholinergic denervation and suggests that the projections from the nucleus basalis of Meynert, which supplies cholinergic innervation to the neocortex, are dysfunctional in iRBD. Longitudinal studies will clarify if these changes are predictive of future cognitive impairment in these patients.

Quantitative evaluation of iron content in idiopathic rapid eye movement sleep behavior disorder.

Idiopathic rapid eye movement sleep behavior disorder is an early sign of neurodegenerative disease. This study aimed to quantitatively evaluate iron content in idiopathic rapid eye movement sleep behavior disorder patients using quantitative susceptibility mapping and to examine the potential of this technique to identify the prodromal stage of α-synucleinopathies. Twenty-five idiopathic rapid eye movement sleep behavior disorder patients, 32 Parkinson's disease patients, and 50 healthy controls underwent quantitative susceptibility mapping. The mean magnetic susceptibility values within the bilateral substantia nigra, globus pallidus, red nucleus, head of the caudate nucleus, and putamen were calculated and compared among groups. The relationships between the values and the clinical features of idiopathic rapid eye movement sleep behavior disorder and Parkinson's disease were measured using correlation analysis. Idiopathic rapid eye movement sleep behavior disorder patients had elevated iron in the bilateral substantia nigra compared with healthy controls. Parkinson's disease patients had increased iron in the bilateral substantia nigra, globus pallidus, and left red nucleus compared with healthy controls and had elevated iron levels in the bilateral substantia nigra compared with idiopathic rapid eye movement sleep behavior disorder patients. Mean magnetic susceptibility values were positively correlated with disease duration in the left substantia nigra in idiopathic rapid eye movement sleep behavior disorder patients. Quantitative susceptibility mapping can detect increased iron in the substantia nigra in idiopathic rapid eye movement sleep behavior disorder, which becomes more significant as the disorder progresses. This technique has the potential to be an early objective neuroimaging marker for detecting α-synucleinopathies. © 2019 International Parkinson and Movement Disorder Society.

Cortical hypoperfusion in patients with idiopathic rapid eye movement sleep behavior disorder detected with arterial spin-labeled perfusion MRI.

Idiopathic rapid eye movement sleep behavior disorder (iRBD) is an important risk factor for α-synucleinopathy. We investigated alterations in the cerebral blood flow (CBF) based on arterial spin-labeled (ASL) imaging in patients with iRBD to determine brain perfusion changes associated with the disorder. Fifteen patients with iRBD and twenty age-gender-matched healthy controls were enrolled. Cortical perfusions were compared between the two groups after the ASL data was co-registered to the high-resolution T1-weighted images. No significant differences were detected between the groups in regard to age, gender, education, or UPDRS-III score. The iRBD group showed a lower MMSE score than the healthy controls (27.07 ± 2.25 vs. 28.55 ± 1.23, p < 0.05). Compared with the healthy controls, the iRBD group showed significantly decreased CBF values in the right inferior frontal gyrus, right middle frontal gyrus, and right insula (p < 0.05 corrected). The cortical hypoperfusion areas in patients with iRBD were similar to the patterns in patients with α -synucleinopathies. ASL perfusion MRI is a potential approach to find biomarkers in preclinical stages of α -synucleinopathies.