Idiopathic Rapid Eye Movement Sleep 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.

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.

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.

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−).

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.

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.

Research progress on neuromolecular imaging of REM sleep behavior disorder.

Idiopathic rapid eye movement sleep behavior disorder (iRBD) is an important non-motor complication of Parkinson's disease. At the same time, iRBD is considered to be the prodromal stage of α-synucleinopathy. This high risk of conversion suggests that iRBD becomes a nerve It is a window for early research on degenerative diseases and is the best candidate for neuroprotection trials. A wide range of neuroimaging techniques has improved our understanding of iRBD as a prodromal stage of the disease. In addition, neuroimaging of abnormal iRBD is expected to be a potential biomarker for predicting clinical phenotypic transformation. This article reviews the research progress of neuromolecular imaging in patients with iRBD from the perspective of iRBD transforming synucleinopathies.

Derivation and Validation of a Phenoconversion-Related Pattern in Idiopathic Rapid Eye Movement Behavior Disorder.

Idiopathic rapid eye movement sleep behavior disorder (iRBD) represents the prodromal stage of α-synucleinopathies. Reliable biomarkers are needed to predict phenoconversion. The aim was to derive and validate a brain glucose metabolism pattern related to phenoconversion in iRBD (iRBDconvRP) using spatial covariance analysis (Scaled Subprofile Model and Principal Component Analysis [SSM-PCA]). Seventy-six consecutive iRBD patients (70 ± 6 years, 15 women) were enrolled in two centers and prospectively evaluated to assess phenoconversion (30 converters, 73 ± 6 years, 14 Parkinson's disease and 16 dementia with Lewy bodies, follow-up time: 21 ± 14months; 46 nonconverters, 69 ± 6 years, follow-up time: 33 ± 19months). All patients underwent [18 F]FDG-PET (18 F-fluorodeoxyglucose positron emitting tomography) to investigate brain glucose metabolism at baseline. SSM-PCA was applied to obtain the iRBDconvRP; nonconverter patients were considered as the reference group. Survival analysis and Cox regression were applied to explore prediction power. First, we derived and validated two distinct center-specific iRBDconvRP that were comparable and significantly able to predict phenoconversion. Then, SSM-PCA was applied to the whole set, identifying the iRBDconvRP. The iRBDconvRP included positive voxel weights in cerebellum; brainstem; anterior cingulate cortex; lentiform nucleus; and middle, mesial temporal, and postcentral areas. Negative voxel weights were found in posterior cingulate, precuneus, middle frontal gyrus, and parietal areas. Receiver operating characteristic analysis showed an area under the curve of 0.85 (sensitivity: 87%, specificity: 72%), discriminating converters from nonconverters. The iRBDconvRP significantly predicted phenoconversion (hazard ratio: 7.42, 95% confidence interval: 2.6-21.4). We derived and validated an iRBDconvRP to efficiently discriminate converter from nonconverter iRBD patients. [18 F]FDG-PET pattern analysis has potential as a phenoconversion biomarker in iRBD patients. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Different patterns of exosomal α-synuclein between Parkinson's disease and probable rapid eye movement sleep behavior disorder.

The insidious onset of Parkinson's disease (PD) makes early diagnosis difficult. Notably, idiopathic rapid eye movement sleep behavior disorder (iRBD) was reported as a prodrome of PD, which may represent a breakthrough for the early diagnosis of PD. However, currently there is no reliable biomarker for PD diagnosis. Considering that α-synuclein (α-Syn) and neuroinflammation are known to develop prior to the onset of clinical symptoms in PD, it was hypothesized that plasma total exosomal α-Syn (t-exo α-Syn), neural-derived exosomal α-Syn (n-exo α-Syn) and exosomal apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) may be potential biomarkers of PD. In this study, 78 PD patients, 153 probable iRBD patients (pRBD) and 63 healthy controls (HCs) were recruited. α-Syn concentrations were measured using a one-step paramagnetic particle-based chemiluminescence immunoassay, and ASC levels were measured using the Ella system. It was found that t-exo α-Syn was significantly increased in the PD group compared to the pRBD and HC groups (p &lt; 0.0001), whilst n-exo α-Syn levels were significantly increased in both the PD and pRBD groups compared to HCs (p &lt; 0.0001). Furthermore, although no difference was found in ASC levels between the PD and pRBD groups, there was a positive correlation between ASC and α-Syn in exosomes. Our results suggest that both t-exo α-Syn and n-exo α-Syn were elevated in the PD group, whilst only n-exo α-Syn was elevated in the pRBD group. Additionally, the adaptor protein of inflammasome ASC is correlated with α-Syn and may facilitate synucleinopathy.

Idiopathic rapid eye movement sleep behavior disorder in Japan: An observational study

IntroductionIdiopathic rapid eye movement sleep behavior disorder (iRBD) is one of the most specific prodromal symptoms of synucleinopathies, including Parkinson's disease (PD) and multiple system atrophy. The Japan Parkinson's Progression Markers Initiative (J-PPMI) was a prospective cohort study conducted in Japanese patients with iRBD to investigate biomarkers for prodromal synucleinopathies. We carried out an initial assessment of the J-PPMI study to reveal the factors correlated with dopamine transporter single-photon emission computed tomography (DaT) and 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy. MethodsThis cross-sectional study was conducted in 108 patients with iRBD, selected from the J-PPMI study. We divided the patients into four groups based on the MIBG and DaT results. We also recorded the patients’ demographics and clinical data. Following PD probability calculation, we examined the biomarkers associated with DaT and MIBG. ResultsNinety-five of the enrolled patients (88%) met the diagnostic criteria for prodromal PD based on the probability score. Only five patients had normal MIBG and DaT. We identified 29 cases with decreased DaT and MIBG, all of whom met the above diagnostic criteria. Both DaT and MIBG were significantly correlated with the Japanese version of the Montreal Cognitive Assessment (MoCA-J) score. ConclusionBoth DaT and MIBG are important biomarkers for confirming synucleinopathies and/or staging disease progression. Although 95% of iRBD patients were consistent with the body-first subtype concept, alpha-synuclein pathologies of iRBD might have widespread systemic involvement rather than being confined to the lower brainstem, particularly in patients with reduced MoCA-J scores.

Which should be a beginning point for the disease duration of idiopathic rapid eye movement sleep behavior disorder, the estimated onset of symptoms, or the date when diagnosed?

Which should be a beginning point for the disease duration of idiopathic rapid eye movement sleep behavior disorder, the estimated onset of symptoms, or the date when diagnosed?

Personality profile and its association with conversion to neurodegenerative disorders in idiopathic REM sleep behavior disorder

Patients with Parkinson’s disease (PD) were described less extraverted and more neurotic. It remained unclear whether similar personality traits could be found in idiopathic rapid eye movement sleep behavior disorder (iRBD), a prodromal stage of PD, and could predict phenoconversion to neurodegenerative disorders. We aimed to investigate the personality profile and its association with future neurodegenerative phenoconversion in iRBD patients. One hundred and eighty-five video-polysomnography confirmed iRBD patients and 91 age- and sex-matched controls underwent personality assessment using the NEO five-factor inventory, and 171 iRBD patients were followed up. Our results showed that iRBD was marginally negatively associated with extraverted personality trait (B = −0.28, 95% confidence interval (CI) = −0.55, −0.001). During a median follow-up of 5.9 years, 47 iRBD patients (27.5%) had phenoconversion. More neurotic (adjusted hazard ratio (HR) = 2.0, 95% CI = 1.3, 3.1) and less extraverted personality traits (adjusted HR = 0.53, 95% CI = 0.36, 0.77) were associated with an increased risk of phenoconversion in iRBD patients. Our findings suggest that personality profile may be a potential prodromal marker of iRBD.

Neuroimaging evidence of glymphatic system dysfunction in possible REM sleep behavior disorder and Parkinson\u2019s disease

Alpha-synucleinopathy is postulated to be central to both idiopathic rapid eye movement sleep behaviour disorder (iRBD) and Parkinson’s disease (PD). Growing evidence suggests an association between the diminished clearance of α-synuclein and glymphatic system dysfunction. However, evidence accumulating primarily based on clinical data to support glymphatic system dysfunction in patients with iRBD and PD is currently insufficient. This study aimed to use diffusion tensor image analysis along the perivascular space (DTI-ALPS) to evaluate glymphatic system activity and its relationship to clinical scores of disease severity in patients with possible iRBD (piRBDs) and those with PD. Further, we validated the correlation between the ALPS index and the prognosis of PD longitudinally. Overall, 168 patients with PD, 119 piRBDs, and 129 healthy controls were enroled. Among them, 50 patients with PD had been longitudinally reexamined. Patients with PD exhibited a lower ALPS index than those with piRBDs (P = 0.036), and both patient groups showed a lower ALPS index than healthy controls (P < 0.001 and P = 0.001). The ALPS index and elevated disease severity were negatively correlated in the piRBD and PD subgroups. Moreover, the ALPS index was correlated with cognitive decline in patients with PD in the longitudinal analyses. In conclusion, DTI-ALPS provided neuroimaging evidence of glymphatic system dysfunction in piRBDs and patients with PD; however, the potential of assessing the pathological progress of α-synucleinopathies as an indicator is worth verifying. Further development of imaging methods for glymphatic system function is also warranted.

Comparative Study on Topological Properties of the Whole-Brain Functional Connectome in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson's Disease Without RBD.

PurposeIdiopathic rapid eye movement Sleep Behavior Disorder (iRBD) is considered as a prodromal and most valuable warning symptom for Parkinson’s disease (PD). Although iRBD and PD without RBD (nRBD-PD) are both α-synucleinopathies, whether they share the same neurodegeneration process is not clear enough. In this study, the pattern and extent of neurodegeneration were investigated and compared between early-stage nRBD-PD and iRBD from the perspective of whole-brain functional network changes.MethodsTwenty-one patients with iRBD, 23 patients with early-stage nRBD-PD, and 22 matched healthy controls (HCs) were enrolled. Functional networks were constructed using resting-state functional MRI (fMRI) data. Network topological properties were analyzed and compared among groups by graph theory approaches. Correlation analyses were performed between network topological properties and cognition in the iRBD and nRBD-PD groups.ResultsBoth patients with iRBD and patients with early-stage nRBD-PD had attention, executive function, and some memory deficits. On global topological organization, iRBD and nRBD-PD groups still presented small-worldness, but both groups exhibited decreased global/local efficiency and increased characteristic path length. On regional topological organization, compared with HC, nRBD-PD presented decreased nodal efficiency, decreased degree centrality, and increased nodal shortest path length, while iRBD presented decreased nodal efficiency and nodal shortest path. For iRBD, brain regions with decreased nodal efficiency were included in the corresponding regions of nRBD-PD. Nodal shortest path changes were significantly different in terms of brain regions and directions between nRBD-PD and iRBD. Attention deficits were correlated with local topological properties of the occipital lobe in both iRBD and nRBD-PD groups.ConclusionBoth global and local efficiency of functional networks declined in nRBD-PD and iRBD groups. The overlaps and differences in local topological properties between nRBD-PD and iRBD indicate that iRBD not only shares functional changes of PD but also presents distinct features.