Idiopathic Rapid Eye Movement Research Articles

Association between serum lipid levels and dopamine loss in idiopathic rapid eye movement sleep behavior disorder

Association between serum lipid levels and dopamine loss in idiopathic rapid eye movement sleep behavior disorder

Idiopathic Rapid Eye Movement Sleep Behavior Disorder (iRBD) Shares Similar Fecal Short-Chain Fatty Acid Alterations with Multiple System Atrophy (MSA) and Parkinson's Disease (PD).

Idiopathic rapid eye movement sleep behavior disorder (iRBD) is considered as a prodromal stage of synucleinopathies. Fecal short-chain fatty acid (SCFA) changes in iRBD and the relationships with synucleinopathies have never been investigated. To investigate fecal SCFA changes among iRBD, multiple system atrophy (MSA), and Parkinson's disease (PD), and evaluate their relationships. Fecal SCFAs and gut microbiota were measured in 29 iRBD, 42 MSA, 40 PD, and 35 normal controls (NC) using gas chromatography-mass spectrometry and 16S rRNA gene sequencing. Compared with NC, fecal SCFA levels (propionic, acetic, and butyric acid) were lower in iRBD, MSA, and PD. Combinations of these SCFAs could differentiate NC from iRBD (AUC 0.809), MSA (AUC 0.794), and PD (AUC 0.701). Decreased fecal SCFAs were associated with the common reducing SCFA-producing gut microbiota in iRBD, MSA, and PD. iRBD shares similar fecal SCFA alterations with MSA and PD, and the combination of these SCFAs might be a potential synucleinopathies-related biomarker. © 2024 International Parkinson and Movement Disorder Society.

Brain Functional Connectivity Changes in Rapid Eye Movement Sleep Behavior Disorder

The idiopathic rapid eye movement sleep behavior disorder (iRBD) has been reported as prodromal biomarker for neurodegenerative synucleinopathies. To early detect neurodegeneration in preclinical stage, pathophysiological changes of iRBD have been studied in many ways including structural magnetic resonance imaging (MRI), functional MRI (fMRI), and connectivity analyses. This review summarizes functional connectivity studies using resting-state fMRI in iRBD patients focused on motor-related network, compensatory mechanism of synucleinopathies, cognitive dysfunction, and non-motor symptoms.

Quantifying cerebral blood flow changes using arterial spin labeling: A comparative study of idiopathic rapid eye movement sleep behavior disorder and Parkinson's disease

IntroductionIdiopathic rapid eye movement sleep behavior disorder (iRBD) and Parkinson's disease (PD) have been found to have changes in cerebral perfusion and overlap of some of the lesioned brain areas. However, a consensus regarding the specific location and diagnostic significance of these cerebral blood perfusion alternations remains elusive in both iRBD and PD. The present study evaluated the patterns of cerebral blood flow changes in iRBD and PD. Material and methodsA total of 59 right-handed subjects were enrolled, including 15 patients with iRBD, 20 patients with PD, and 24 healthy controls (HC). They were randomly divided into groups at a ratio of 4 to 1 for training and testing. A PASL sequence was employed to obtain quantitative cerebral blood flow (CBF) maps. The CBF values were calculated from these acquired maps. In addition, AutoGluon was employed to construct a classifier for CBF features selection and classification. An independent t-test was performed for CBF variations, with age and sex as nuisance variables. The performance of the feature was evaluated using receiver operating characteristic (ROC) curves. A significance level of P < 0.05 was considered significant. CBF in several brain regions, including the left median cingulate and paracingulate gyri and the right middle occipital gyrus (MOG), showed significant differences between PD and HC, demonstrating good classification performance. The combined model that integrates all features achieved even higher performance with an AUC of 0.9380. Additionally, CBF values in multiple brain regions, including the right MOG and the left angular gyrus, displayed significant differences between PD and iRBD. Particularly, CBF values in the left angular gyrus exhibited good performance in classifying PD and iRBD. The combined model achieved improved performance, with an AUC of 0.8533. No significant differences were found in brain regions when comparing CBF values between iRBD and HC subjects. ConclusionsASL-based quantitative CBF change features can offer reliable biomarkers to assist in the diagnosis of PD. Regarding the characteristic of CBF in the right MOG, it is anticipated to serve as an imaging biomarker for predicting the progression of iRBD to PD.

Mitochondrial DNA deletions in the cerebrospinal fluid of patients with idiopathic REM sleep behaviour disorder

Idiopathic rapid eye movement (REM) sleep behaviour disorder (IRBD) represents the prodromal stage of Lewy body disorders (Parkinson's disease (PD) and dementia with Lewy bodies (DLB)) which are linked to variations in circulating cell-free mitochondrial DNA (cf-mtDNA). Here, we assessed whether altered cf-mtDNA release and integrity are already present in IRBD. We used multiplex digital PCR (dPCR) to quantify cf-mtDNA copies and deletion ratio in cerebrospinal fluid (CSF) and serum in a cohort of 71 participants, including 1) 17 patients with IRBD who remained disease-free (non-converters), 2) 34 patients initially diagnosed with IRBD who later developed either PD or DLB (converters), and 3) 20 age-matched controls without IRBD or Parkinsonism. In addition, we investigated whether CD9-positive extracellular vesicles (CD9-EVs) from CSF and serum samples contained cf-mtDNA. Patients with IRBD, both converters and non-converters, exhibited more cf-mtDNA with deletions in the CSF than controls. This finding was confirmed in CD9-EVs. The high levels of deleted cf-mtDNA in CSF corresponded to a significant decrease in cf-mtDNA copies in CD9-EVs in both IRBD non-converters and converters. Conversely, a significant increase in cf-mtDNA copies was found in serum and CD9-EVs from the serum of patients with IRBD who later converted to a Lewy body disorder. Alterations in cf-mtDNA copy number and deletion ratio known to occur in Lewy body disorders are already present in IRBD and are not a consequence of Lewy body disease conversion. This suggests that mtDNA dysfunction is a primary molecular mechanism of the pathophysiological cascade that precedes the full clinical motor and cognitive manifestation of Lewy body disorders. Funded by Michael J. Fox Foundation research grant MJFF-001111. Funded by MICIU/AEI/10.13039/501100011033 "ERDF A way of making Europe", grants PID2020-115091RB-I00 (RT) and PID2022-143279OB-I00 (ACo). Funded by Instituto de Salud Carlos III and European Union NextGenerationEU/PRTR, grant PMP22/00100 (RT and ACo). Funded by AGAUR/Generalitat de Catalunya, grant SGR00490 (RT and ACo). MP has an FPI fellowship, PRE2018-083297, funded by MICIU/AEI/10.13039/501100011033 "ESF Investing in your future".

Dreaming Characteristics in Non-Rapid Eye Movement Parasomnia and Idiopathic Rapid Eye Movement Sleep Behaviour Disorder: Similarities and Differences.

Speech graph analysis (SGA) of dreams has recently shown promise as an objective and language-invariant diagnostic tool that can aid neuropsychiatric diagnosis. Whilst the notion that dreaming mentations reflect distinct physiologic processes is not new, such studies in patients with sleep disorders remain exceptionally scarce. Here, using SGA and other dream content analyses, we set to investigate structural and thematic differences in morning dream recalls of patients diagnosed with Non-Rapid Eye Movement Parasomnia (NREMP) and Idiopathic REM Sleep Behavior Disorder (iRBD). A retrospective cross-sectional study of morning dream recalls of iRBD and NREMP patients was undertaken. Traditional dream content analyses, such as Orlinsky and Hall and Van de Castle analyses, were initially conducted. Subsequently, SGA was performed in order to objectively quantify structural speech differences between the dream recalls of the two patient groups. Comparable rate of morning recall of dreams in the sleep laboratory was recorded; 25% of iRBD and 18.35% of NREMP patients. Aggression in dreams was recorded by 28.57% iRBD versus 20.00% in NREMP group. iRBD patients were more likely to recall dreams (iRBD vs NREMP; P = 0.007), but they also had more white dreams, ie having a feeling of having dreamt, but with no memory of it. Visual and quantitative graph speech analyses of iRBD dreams suggested stable sequential structure, reflecting the linearity of the chronological narrative. Conversely, NREMP dream reports displayed more recursive, less stable systems, with significantly higher scores of graph connectivity measures. The findings of our exploratory study suggest that iRBD and NREMP patients may not only differ on what is recalled in their dreams but also, perhaps more strikingly, on how dreams are recalled. It is hoped that future SGA-led dream investigations of larger groups of patients will help discern distinct mechanistic underpinnings and any associated clinical implications.

Reading the mind in the eyes in patients with idiopathic REM sleep behavior disorder.

Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is characterized by vocalizations, jerks, and motor behaviors during REM sleep, often associated with REM-related dream content, which is considered a prodromal stage of α-synucleinopathy. The results of the Reading the Mind in the Eyes (RME) reflecting affective Theory of Mind (ToM) are inconsistent in α-synucleinopathy. The present study tried to investigate the RME in patients with iRBD. A total of 35 patients with iRBD and 26 healthy controls were included in the study. All participants were administered the RME and the cognitive assessments according to a standard procedure. The patients with iRBD were further divided into two groups (high or low RME) according to the scores of the RME (> 21, or ≤ 20). The patients with iRBD had worse scores on cognitive tests compared with healthy controls involving global cognitive screening, memory, and visuospatial abilities (p < 0.05), but the scores of the RME were similar between the two groups (20.83 ± 3.38, 20.58 ± 3.43) (p ˃ 0.05). Patients with low RME had more obvious cognitive impairments than healthy controls. After applying Bonferroni correction for multiple tests, the low REM group only performed worse on the Sum of trials 1 to 5 and delayed recall of the RAVLT compared with the healthy control group (p < 0.001, = 0.002). The RME correlated with the scores of cognitive tests involving executive function, attention, memory, and visuospatial function. The changes in RME had a relationship with cognitive impairments, especially memory, in patients with iRBD.

Predictive biomarkers for cognitive decline in patients with idiopathic REM sleep behavior disorder

AbstractBackgroundIdiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is regarded as an early stage of the synucleinopathy, which may precede the onset of cognitive impairment or parkinsonism. Biomarkers for cognitive decline in patients with iRBD would be helpful to early intervention. Our aim was to identify biomarkers for predicting the cognitive deterioration risk in patients with iRBD.MethodWe involved patients with polysomnographically confirmed iRBD who has at least 2 visits from the Parkinson’s Progression Markers Initiative (PPMI) database. Progression of cognitive state to MCI or dementia during follow‐up was defined as the endpoint. Baseline clinical features, biofluid and genetic biomarkers were compared between iRBD with or without progression of cognitive decline. Predictive biomarkers were identified with Kaplan‐Meier and Cox proportional hazards analysis, adjusting for age, sex, and years of education.ResultA total of 38 patients with iRBD were enrolled (average age: 69.53 ± 5.54, male: 84.21%) . During follow‐up (median 5.45, IQR 4.08‐7.1 years), Progression of cognitive decline occurred in 57.89% (22/38) patients with iRBD. Baseline clinical features including hallucinations and psychosis (HR = 13.783, p = 0.022) and higher confidence abnormalities consistent with a neurodegenerative parkinsonian syndrome (HR = 2.258, p = 0.017) increased the risk. Patients with a lower loge‐transformed the ratio of Aβ 1‐42 in cerebrospinal fluid (CSF) to ΝfL in serum (Aβ/NfL, HR = 0.375, p = 0.044) and t‐tau in CSF to ΝfL in serum (t‐tau/NfL, HR = 0.277, p = 0.044) had a higher risk of cognitive decline. Genetic biomarkers consisting of GBA rs75548401(HR = 13.783, p = 0.022), STK39 rs1955337 (HR = 11.882, p&lt;0.001), and COMT rs4680 (HR = 2.376, p = 0.021) variants increased the risk, while MCCC1 rs12637471 (HR = 0.408, p = 0.024), COMT rs165656 (HR = 0.451, p = 0.033), COMT rs4633 (HR = 0.421, p = 0.021), and COMT rs165599 (HR = 0.427, p = 0.023) variants decreased the risk. A model combining age and variables with p&lt;0.05 exhibited above presented the best predictive performance, with an AUC of 0.963 (95% CI 0.896–1.000, p&lt;0.001).ConclusionOur findings provide potential biomarkers to evaluate the risk of progression to MCI or dementia in patients with iRBD. Combination of clinical features, biofluid and genetic biomarkers performs optimal predicting accuracy.

Impaired Mitochondrial Respiration in REM-Sleep Behavior Disorder: A Biomarker of Parkinson's Disease?

Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is associated with prodromal Parkinson's disease (PD), but the mechanisms linking phenoconversion of iRBD to PD have not yet been clarified. Considering the association between mitochondrial dysfunction and sleep disturbances in PD, we explored mitochondrial activity in fibroblasts derived from iRBD patients to identify a biochemical profile that could mark the presence of impending neurodegeneration. The study involved 28 participants, divided into three groups: patients diagnosed with iRBD, PD patients converted from iRBD (RBD-PD), and healthy controls. We performed a comprehensive assessment of mitochondrial function, including an examination of mitochondrial morphology, analysis of mitochondrial protein expression levels by western blot, and measurement of mitochondrial respiration using the Seahorse XFe24 analyzer. In basal conditions, mitochondrial respiration did not differ between iRBD and control fibroblasts, but when cells were challenged with a higher energy demand, iRBD fibroblasts exhibited a significant (P = 0.006) drop in maximal and spare respiration compared to controls. Interestingly, RBD-PD patients showed the same alterations with a further significant reduction in oxygen consumption linked to adenosine triphosphate production (P = 0.032). Moreover, RBD-PD patients exhibited a significant decrease in protein levels of complexes III (P = 0.02) and V (P = 0.002) compared to controls, along with fragmentation of the mitochondrial network. iRBD patients showed similar, but milder alterations. Altogether, these findings suggest that mitochondrial dysfunctions in individuals with iRBD might predispose to worsening of the bioenergetic profile observed in RBD-PD patients, highlighting these alterations as potential predictors of phenoconversion to PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A Study on the Evaluation of Brainstem Dysfunction in Rapid Eye Movement Sleep Behavior Disorder Using Video Nystagmography

Background: This study aimed to differentiate video nystagmography (VNG) characteristics, including the video head impulse test (vHIT), in patients with idiopathic rapid eye movement behavior disorder (RBD) from healthy controls, which is considered a precursor to degenerative diseases.Methods: One hundred eighty-five patients underwent overnight polysomnography (PSG) and VNG. Based on overnight PSG, 27 patients with RBD or REM sleep without atonia (RWA) and AHI&lt;15 were categorized into the RBD group, 34 patients with RBD/RWA and AHI≥15 were grouped into the combined group. Sixty patients with AHI≥15 and no RBD/RWA were included in the obstructive sleep apnea (OSA) group, and 64 negative participants were assigned to the control group. In VNG, we measured the gain of vHIT in each canal, with the latency, amplitude, and velocity of horizontal saccades and smooth pursuit. We compared the results between groups using ANOVA, after normalization and adjustment for age and sex.Results: The gain of vHIT in the left horizontal canal was decreased in the RBD group, but it was more pronounced in the OSA group. Elevated gain of the left posterior canal was seen in the RBD group, but technical errors were attributable. The RBD group displayed prolonged latency of saccade on the left side and slowed saccade on the right side, but these were statistically insignificant.Conclusions: The VNG study revealed differences between the sleep disorders, potentially reflecting brainstem function in each disorder. However, these differences lacked statistical significance. We anticipate that significant results could be obtained with more controlled conditions.

Clinical and dopaminergic imaging characteristics of the FARPRESTO cohort of trial-ready idiopathic rapid eye movement sleep behavior patients.

Idiopathic/isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is considered the prodromal stage of alpha-synucleinopathies. Thus, iRBD patients are the ideal target for disease-modifying therapy. The risk FActoRs PREdictive of phenoconversion in iRBD Italian STudy (FARPRESTO) is an ongoing Italian database aimed at identifying risk factors of phenoconversion, and eventually to ease clinical trial enrollment of well-characterized subjects. Polysomnography-confirmed iRBD patients were retrospectively and prospectively enrolled. Baseline harmonized clinical and nigrostriatal functioning data were collected at baseline. Nigrostriatal functioning was evaluated by dopamine transporter-single-photon emission computed tomography (DaT-SPECT) and categorized with visual semi-quantification. Longitudinal data were evaluated to assess phenoconversion. Cox regressions were applied to calculate hazard ratios. 365 patients were enrolled, and 289 patients with follow-up (age 67.7 ± 7.3 years, 237 males, mean follow-up 40 ± 37 months) were included in this study. At follow-up, 97 iRBD patients (33.6%) phenoconverted to an overt synucleinopathy. Older age, motor and cognitive impairment, constipation, urinary and sexual dysfunction, depression, and visual semi-quantification of nigrostriatal functioning predicted phenoconversion. The remaining 268 patients are in follow-up within the FARPRESTO project. Clinical data (older age, motor and cognitive impairment, constipation, urinary and sexual dysfunction, depression) predicted phenoconversion in this multicenter, longitudinal, observational study. A standardized visual approach for semi-quantification of DaT-SPECT is proposed as a practical risk factor for phenoconversion in iRBD patients. Of note, non-converted and newly diagnosed iRBD patients, who represent a trial-ready cohort for upcoming disease-modification trials, are currently being enrolled and followed in the FARPRESTO study. New data are expected to allow better risk characterization.

Iron accumulation in the ventral tegmental area in Parkinson's disease.

The ventral tegmental area (VTA) is less affected compared to substantia nigra pars compacta (SNc) in Parkinson's disease (PD). This study aimed to quantitatively evaluate iron content in the VTA across different stages of PD in order to help explain the selective loss of dopamine neurons in PD. Quantitative susceptibility mapping (QSM) data were obtained from 101 PD patients, 35 idiopathic rapid eye movement sleep behavior disorder (RBD) patients, and 62 healthy controls (HCs). The mean QSM values in the VTA and SNc were calculated and compared among the groups. Both RBD and PD patients had increased iron values in the bilateral SNc compared with HCs. RBD and PD patients in the Hoehn-Yahr (H & Y) stage 1 did not show elevated iron values in the VTA, while PD patients with more than 1.5 H & Y staging had increased iron values in bilateral VTA compared to HCs. This study shows that there is no increased iron accumulation in the VTA during the prodromal and early clinical stages of PD, but iron deposition increases significantly as the disease becomes more severe.

Increased Free Water in the Putamen in Idiopathic REM Sleep Behavior Disorder.

It has been suggested that the loss of nigrostriatal dopaminergic axon terminals occurs before the loss of dopaminergic neurons in the substantia nigra (SN) in Parkinson's disease (PD). This study aimed to use free-water imaging to evaluate microstructural changes in the dorsoposterior putamen (DPP) of idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) patients, which is considered a prodromal stage of synucleinopathies. Free water values in the DPP, dorsoanterior putamen (DAP), and posterior SN were compared between the healthy controls (n = 48), iRBD (n = 43) and PD (n = 47) patients. In iRBD patients, the relationships between baseline and longitudinal free water values and clinical manifestations or dopamine transporter (DAT) striatal binding ratio (SBR) were analyzed. Free water values were significantly higher in the DPP and posterior substantia nigra (pSN), but not in the DAP, in the iRBD and PD groups than in controls. In iRBD patients, free water values in the DPP were progressively increased and correlated with the progression of clinical manifestations and the striatal DAT SBR. Baseline free water in the DPP was negatively correlated with striatal DAT SBR and hyposmia and positively correlated with motor deficits. This study demonstrates that free water values in the DPP are increased cross-sectionally and longitudinally and associated with clinical manifestations and the function of the dopaminergic system in the prodromal stage of synucleinopathies. Our findings indicate that free-water imaging of the DPP has the potential to be a valid marker of early diagnosis and progression of synucleinopathies. © 2023 International Parkinson and Movement Disorder Society.

Neurofilament Light Protein Predicts Disease Progression in Idiopathic REM Sleep Behavior Disorder.

Idiopathic rapid eye movement sleep behavior disorder (iRBD) is increasingly recognized as a manifestation preceding the α-synucleinopathies like Parkinson's disease (PD). Neurofilament light chain (NfL) have been reported to be higher in synucleinopathies as a sign of neurodegeneration. To evaluate whether plasma NfL is valuable in reflecting cognitive and motor status in iRBD and PD with a premorbid history of RBD (PDRBD), and predicting disease progression in iRBD. Thirty-one patients with iRBD, 30 with PDRBD, and 18 healthy controls were included in the cross-sectional and prospective study. Another cohort from the Parkinson's Progression Markers Initiative (PPMI) dataset was enrolled for verification analysis. All patients received evaluations of cognitive, motor, and autonomic function by a battery of clinical tests at baseline and follow-up. Blood NfL was measured by the Quanterix Simoa HD-1. In our cohort, 26 patients with iRBD completed the follow-up evaluations, among whom eight (30.8%) patients displayed phenoconversion. Baseline plasma NfL cutoff value of 22.93 pg/mL performed best in distinguishing the iRBD converters from non-converters (sensitivity: 75.0%, specificity: 83.3%, area under the curve: 0.84). Cognitive and motor function were significantly correlated with NfL levels in PDRBD (correlation coefficients: -0.379, 0.399; respectively). Higher baseline NfL levels in iRBD were significantly associated with higher risks for cognitive, motor, autonomic function progression, and phenoconversion at follow-up (hazard ratios: 1.069, 1.065, 1.170, 1.065; respectively). The findings were supported by the PPMI dataset. Plasma NfL is valuable in reflecting disease severity of PDRBD and predicting disease progression and phenoconversion in iRBD.

Disruption of locus coeruleus-related functional networks in Parkinson’s disease

Locus coeruleus (LC) is severely affected in Parkinson’s Disease (PD). However, alterations in LC-related resting-state networks (RSNs) in PD remain unclear. We used resting-state functional MRI to investigate the alterations in functional connectivity (FC) of LC-related RSNs and the associations between RSNs changes and clinical features in idiopathic rapid eye movement sleep behavior disorder (iRBD) and PD patients with (PDRBD+) and without RBD (PDRBD−). There was a similarly disrupted FC pattern of LC-related RSNs in iRBD and PDRBD+ patients, whereas LC-related RSNs were less damaged in PDRBD− patients than that in patients with iRBD and PDRBD+. The FC of LC-related RSNs correlated with cognition and duration in iRBD, depression in PDRBD−, and cognition and severity of RBD in patients with PDRBD+. Our findings demonstrate that LC-related RSNs are significantly disrupted in the prodromal stage of α-synucleinopathies and proposed body-first PD (PDRBD+), but are less affected in brain-first PD (PDRBD−).

0716 Quality of Life in Idiopathic REM Sleep Behavior Disorder and Isolated REM Sleep Without Atonia

Abstract Introduction Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) can affect quality of life (QOL) for both patient and bed partner; isolated REM sleep without atonia (iRSWA) has been less well-studied. We aimed to investigate whether QOL changes over time in those with either iRBD or iRSWA, as well as compare these changes to one another. Additionally, we attempted to demonstrate whether certain QOL changes were associated with phenoconversion to neurodegenerative illness. Methods We prospectively analyzed data from the “REM Sleep Behavior Disorder Associations with Parkinson’s Disease Study (RAPiDS)” cohort both at baseline and then at follow-up evaluations. We utilized the Neuro-QOL self-reported questionnaire to ascertain subjects’ level of QOL. Results There were 6 with iRSWA and 33 with iRBD, with an average age of 61.9 ± 13.0 years, with 13 women and 26 men. Significant QOL changes were found in both iRSWA and iRBD group. Among those who phenoconverted, fatigue and social functioning were the main QOL issues that that worsened over time. Conclusion This is the first time the Neuro-QOL has been studied in iRBD and iRSWA. QOL can be affected in both conditions; fatigue and social functioning seem to be of particular importance as they may be associated with phenoconversion. Support (if any) Grant from a private individual

Comparative Analysis of Pupillometry in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson’s Disease

Background and Objective Pupillary light reflex (PLR) abnormalities have been reported in patients with Parkinson’s disease (PD). However, few studies have been conducted on the abnormality of PLR in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD), which is a prodromal stage of α-synucleinopathy. We herein quantitatively analyzed the PLR of iRBD using an automated pupillometer, and compared the results with those of PD.Methods In this cross-sectional study, we prospectively enrolled 27 patients with polysomnography-confirmed iRBD, and 23 patients with PD. Pupillometry was performed three times in each eye, alternating left and right. We compared seven pupillometric parameters between the iRBD and PD patients.Results Maximum and minimum pupil diameters were significantly larger in PD patients than in iRBD patients. However, the other pupillometric parameters, such as mean constriction velocity, maximum constriction velocity, reflex amplitude, latency, and mean dilation velocity, did not differ between the two groups. Among iRBD patients, the pupillometric parameters were not correlated with any clinical characteristics related to autonomic dysfunction or neurodegeneration.Conclusions We found that the pupillary constriction and dilation in response to light of iRBD were not different from those of PD. These findings suggest that autonomic pupillary dysfunction already existed in the prodromal stage of α-synucleinopathy to a degree comparable to that in PD. Larger pupil diameters in PD than in iRBD may reflect the pharmacological effect of dopaminergic medications. Future studies are needed to elucidate the association between the PLR abnormalities and the risk of phenoconversion in iRBD.

Gut microbiota in dementia with Lewy bodies.

Gut microbiota and fecal bile acids were analyzed in 278 patients with α-synucleinopathies, which were comprised of 28 patients with dementia with Lewy bodies (DLB), 224 patients with Parkinson's disease (PD), and 26 patients with idiopathic rapid eye movement sleep behavior disorder (iRBD). Similarly to PD, short-chain fatty acids-producing genera were decreased in DLB. Additionally, Ruminococcus torques and Collinsella were increased in DLB, which were not changed in PD. Random forest models to differentiate DLB and PD showed that high Ruminococcus torques and high Collinsella, which presumably increase intestinal permeability, as well as low Bifidobacterium, which are also observed in Alzheimer's disease, were predictive of DLB. As Ruminococcus torques and Collinsella are also major secondary bile acids-producing bacteria, we quantified fecal bile acids and found that the production of ursodeoxycholic acid (UDCA) was high in DLB. Increased UDCA in DLB may mitigate neuroinflammation at the substantia nigra, whereas neuroinflammation may not be critical at the neocortex. Theraeutic intervention to increase Bifidobacteirum and its metabolites may retard the development and progression of DLB.

Obstructive sleep apnea may reduce a diagnostic accuracy of video-polysomnography for idiopathic REM sleep behavior disorder

BackgroundSevere obstructive sleep apnea (OSA) in patients with rapid eye movement (REM) sleep behavior disorder (RBD) may result in frequent fragmentation of REM sleep and consequently lead to a false negative diagnosis of RBD on a video-polysomnography (video-PSG). Thus, we determined whether OSA has the negative impact on video-PSG diagnostic accuracy for RBD. MethodsPatients with clinically diagnosed idiopathic RBD were included. RBD was confirmed if a video-PSG demonstrated complex motor behavior during REM sleep or REM sleep without atonia (RWA). Motor behavior was measured using the RBD Severity Scale. Cohen's kappa coefficient was calculated for qualitative assessment of RWA. A stepwise logistic regression analysis was performed. ResultsOf a total 254 patients included, a diagnosis of RBD was confirmed by a video-PSG in 221 patients (87.0%). RWA, vocalization, and axial or proximal muscle movements in REM sleep were noted in 86.6%, 58.3%, and 35.9%, respectively. A video-PSG diagnosis of RBD was less likely associated with severe OSA (odds ratio [OR] 0.284, p = 0.010) and moderate OSA (OR 0.404, p = 0.071) whereas was more likely associated with longer REM sleep time (OR 1.036, p < 0.001). In 43 patients who underwent a continuous positive airway pressure (CPAP) titration study, a diagnosis of RBD was more common on a CPAP titration study (88.4%) than on a first video-PSG (65.1%) (p = 0.013). Twelve (27.9%) of 43 CPAP patients were diagnosed with RBD according only to CPAP titration study. ConclusionsOSA that requires CPAP may reduce a diagnostic accuracy for RBD by a video-PSG. False negative results were probably due to frequent electromyographic artifacts and/or severe sleep disruption from apneic events during REM sleep.

Reward insensitivity is associated with dopaminergic deficit in rapid eye movement sleep behaviour disorder.

Idiopathic rapid eye movement sleep behaviour disorder (iRBD) has now been established as an important marker of the prodromal stage of Parkinson's disease and related synucleinopathies. However, although dopamine transporter single photon emission computed tomography (SPECT) has been used to demonstrate the presence of nigro-striatal deficit in iRBD, quantifiable correlates of this are currently lacking. Sensitivity to rewarding stimuli is reduced in some people with Parkinson's disease, potentially contributing to aspects of the neuropsychiatric phenotype in these individuals. Furthermore, a role for dopaminergic degeneration is suggested by the fact that reward insensitivity can be improved by dopaminergic medications. Patients with iRBD present a unique opportunity to study the relationship between reward sensitivity and early dopaminergic deficit in the unmedicated state. Here, we investigate whether a non-invasive, objective measure of reward sensitivity might be a marker of dopaminergic status in prodromal Parkinson's disease by comparing with SPECT/CT measurement of dopaminergic loss in the basal ganglia. Striatal dopaminergic deficits in iRBD are associated with progression to Parkinsonian disorders. Therefore, identification of a clinically measurable correlate of this degenerative process might provide a basis for the development of novel risk stratification tools. Using a recently developed incentivized eye-tracking task, we quantified reward sensitivity in a cohort of 41 patients with iRBD and compared this with data from 40 patients with Parkinson's disease and 41 healthy controls. Patients with iRBD also underwent neuroimaging with dopamine transporter SPECT/CT. Overall, reward sensitivity, indexed by pupillary response to monetary incentives, was reduced in iRBD cases compared with controls and was not significantly different to that in patients with Parkinson's disease. However, in iRBD patients with normal dopamine transporter SPECT/CT imaging, reward sensitivity was not significantly different from healthy controls. Across all iRBD cases, a positive association was observed between reward sensitivity and dopaminergic SPECT/CT signal in the putamen. These findings demonstrate a direct relationship between dopaminergic deficit and reward sensitivity in patients with iRBD and suggest that measurement of pupillary responses could be of value in models of risk stratification and disease progression in these individuals.