REM Sleep Behavior Disorder Patients Research Articles

Automatic quantification of REM sleep without atonia reliably identifies patients with REM sleep behavior disorder: a possible screening tool?

REM Sleep Behavior Disorder (RBD) is characterized by absence of physiological muscle atonia during REM sleep (REM sleep without atonia, RWA). Nigro-striatal dopaminergic impairment is a feature of Parkinson disease (PD) and can be identified in prodromal stages as well, such as idiopathic RBD (iRBD). Aims of this study are to explore the efficacy of an automatic RWA quantification in identifying RBD patients and the correlation between RWA and nigro-striatal dopaminergic function. Forty-five iRBD, 46 PD with RBD, 24 PD without RBD patients and 11 healthy controls were enrolled in the Genoa Center (group A) and 25 patients with iRBD (group B) were enrolled in the Danish Center. Group A underwent brain [123I]FP-CIT-SPECT and group B underwent brain [18F]PE2I-PET as measures of nigro-striatal dopaminergic function. Chin muscle activity was recorded in all subjects and analyzed by applying a published automatic algorithm. Correlations between RWA and nigro-striatal dopaminergic function were explored. The automatic quantification of RWA significantly differentiated RBD from non-RBD subjects (AUC = 0.86), although with lower accuracy compared with conventional visual scoring (AUC = 0.99). No significant correlation was found between RWA and nigro-striatal dopaminergic function. The automatic quantification of RWA is a reliable tool to identify subjects with RBD and may be used as a first-line screening tool, but without correlations with nigro-striatal dopaminergic functioning.

Microglial Activation and Progression of Nigrostriatal Dysfunction in Isolated REM Sleep Behavior Disorder.

Using 11 C-(R)-PK11195-PET, we found increased microglia activation in isolated REM sleep behavior disorder (iRBD) patients. Their role remains to be clarified. The objective is to assess relationships between activated microglia and progression of nigrostriatal dysfunction in iRBD. Fifteen iRBD patients previously scanned with 11 C-(R)-PK11195 and 18 F-DOPA-PET underwent repeat 18 F-DOPA-PET after 3 years. 18 F-DOPA Ki changes from baseline were evaluated with volumes-of-interest and voxel-based analyses. Significant 18 F-DOPA Ki reductions were found in putamen and caudate. Reductions were larger and more widespread in patients with increased nigral microglia activation at baseline. Left nigral 11 C-(R)-PK11195 binding at baseline was a predictor of 18 F-DOPA Ki reduction in left caudate (coef = -0.0426, P = 0.016). Subjects with increased baseline 11 C-(R)-PK11195 binding have greater changes in nigrostriatal function, suggesting a detrimental rather than protective effect of microglial activation. Alternatively, both phenomena occur in patients with prominent nigrostriatal dysfunction without a causative link. The clinical and therapeutic implications of these findings need further elucidation. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Presynaptic Dopaminergic Imaging Characterizes Patients with REM Sleep Behavior Disorder Due to Synucleinopathy.

To apply a machine learning analysis to clinical and presynaptic dopaminergic imaging data of patients with rapid eye movement (REM) sleep behavior disorder (RBD) to predict the development of Parkinson disease (PD) and dementia with Lewy bodies (DLB). In this multicenter study of the International RBD study group, 173 patients (mean age 70.5 ± 6.3 years, 70.5% males) with polysomnography-confirmed RBD who eventually phenoconverted to overt alpha-synucleinopathy (RBD due to synucleinopathy) were enrolled, and underwent baseline presynaptic dopaminergic imaging and clinical assessment, including motor, cognitive, olfaction, and constipation evaluation. For comparison, 232 RBD non-phenoconvertor patients (67.6 ± 7.1 years, 78.4% males) and 160 controls (68.2 ± 7.2 years, 53.1% males) were enrolled. Imaging and clinical features were analyzed by machine learning to determine predictors of phenoconversion. Machine learning analysis showed that clinical data alone poorly predicted phenoconversion. Presynaptic dopaminergic imaging significantly improved the prediction, especially in combination with clinical data, with 77% sensitivity and 85% specificity in differentiating RBD due to synucleinopathy from non phenoconverted RBD patients, and 85% sensitivity and 86% specificity in discriminating PD-converters from DLB-converters. Quantification of presynaptic dopaminergic imaging showed that an empirical z-score cutoff of -1.0 at the most affected hemisphere putamen characterized RBD due to synucleinopathy patients, while a cutoff of -1.0 at the most affected hemisphere putamen/caudate ratio characterized PD-converters. Clinical data alone poorly predicted phenoconversion in RBD due to synucleinopathy patients. Conversely, presynaptic dopaminergic imaging allows a good prediction of forthcoming phenoconversion diagnosis. This finding may be used in designing future disease-modifying trials. ANN NEUROL 2024.

Gender Difference in REM Sleep Behavior Disorder in Japanese Population: Polysomnography and Sleep Questionnaire Study

Rapid eye movement (REM) sleep behavior disorder (RBD) is generally common among males and is an established risk factor for neurodegenerative diseases. As the population ages, the prevalence of α-synucleinopathy (such as Parkinson’s disease) is increasing. Additionally, the number of female patients is increasing in Japan. Therefore, we aimed to clarify the clinical characteristics of RBD from the perspective of gender differences in the Japanese population. The proportion of male RBD patients (65.2%) was significantly higher than that of female patients (34.8%). Additionally, female patients (70.5 ± 8.2 years) were significantly older than male patients (67.9 ± 8.0 years, p < 0.05). The mean score on the RBD Screening Questionnaire was significantly higher in male patients than in female (8.6 ± 2.9 vs. 7.7 ± 3.1, p < 0.05), while the mean score on the Pittsburgh Sleep Quality Index was significantly higher in males (5.9 ± 3.8 vs. 7.2 ± 3.600, p < 0.001). The Self-rating Depression Scale in females was 41.7 ± 8.5, and they were more likely to show depressive tendencies than males. In polysomnography, higher rates of obstructive sleep apnea and longer duration of stage N1 sleep were detected in males. After adjusting for age, BMI, and polysomnographic parameters, we found that female RBD patients had significantly worse sleep quality and rates of depression compared to male patients.

Role of sleep in neurodegeneration: the consensus report of the 5th Think Tank World Sleep Forum.

Sleep abnormalities may represent an independent risk factor for neurodegeneration. An international expert group convened in 2021 to discuss the state-of-the-science in this domain. The present article summarizes the presentations and discussions concerning the importance of a strategy for studying sleep- and circadian-related interventions for early detection and prevention of neurodegenerative diseases. An international expert group considered the current state of knowledge based on the most relevant publications in the previous 5years; discussed the current challenges in the field of relationships among sleep, sleep disorders, and neurodegeneration; and identified future priorities. Sleep efficiency and slow wave activity during non-rapid eye movement (NREM) sleep are decreased in cognitively normal middle-aged and older adults with Alzheimer's disease (AD) pathology. Sleep deprivation increases amyloid-β (Aβ) concentrations in the interstitial fluid of experimental animal models and in cerebrospinal fluid in humans, while increased sleep decreases Aβ. Obstructive sleep apnea (OSA) is a risk factor for dementia. Studies indicate that positive airway pressure (PAP) treatment should be started in patients with mild cognitive impairment or AD and comorbid OSA. Identification of other measures of nocturnal hypoxia and sleep fragmentation could better clarify the role of OSA as a risk factor for neurodegeneration. Concerning REM sleep behavior disorder (RBD), it will be crucial to identify the subset of RBD patients who will convert to a specific neurodegenerative disorder. Circadian sleep-wake rhythm disorders (CSWRD) are strong predictors of caregiver stress and institutionalization, but the absence of recommendations or consensus statements must be considered. Future priorities include to develop and validate existing and novel comprehensive assessments of CSWRD in patients with/at risk for dementia. Strategies for studying sleep-circadian-related interventions for early detection/prevention of neurodegenerative diseases are required. CSWRD evaluation may help to identify additional biomarkers for phenotyping and personalizing treatment of neurodegeneration.

The Increasing Prevalence of REM Sleep Behavior Disorder with Parkinson's Disease Progression: A Polysomnography‐Supported Study

AbstractObjectivesRapid eye movement (REM) sleep behavior disorder (RBD) is proposed as an early diagnostic marker in Parkinson's disease (PD). We investigated the frequency of RBD during the progression of PD in the advanced stages and identified potential risk factors for developing RBD earlier or later.Patients and MethodsWe performed a retrospective analysis and determined the frequency of RBD in all PD in‐patients (Hoehn and Yahr stages ≥3) with motor fluctuations who had undergone video‐polysomnography (vPSG) for a sleep complaint or daytime sleepiness. To correct for selection bias, we analyzed the prevalence of RBD in PD patients from the DeNoPa cohort. PD patients with RBD were compared with PD without RBD. To identify potential risk factors, we performed multiple regression modeling.ResultsA total of 504 PD patients had vPSG. 37 were excluded due to missing REM or artifacts during REM. RBD was present in 406/467 (86.9%) PD patients. PD + RBD patients were older than PDnonRBD (69 ± 7.7 vs. 64 ± 9.2 years, P < 0.01), were more likely to have postural instability [234 (59.1%) vs. 19 (33.9%), P < 0.01], and were treated more often with antidepressants (other than SSRIs) [141 (34.7%) vs. 7 (13%), P < 0.01]. Multiple regression modeling identified predictors of RBD with an AUC of 0.78.ConclusionThe prevalence of RBD in patients with advanced PD is high and increases with disease severity, motor deficits, postural instability, orthostatic symptoms, and age. This suggests RBD is a progression marker of PD in patients with sleep complaints.

To know or not to know? Opinions of patients with Parkinson's Disease on disclosing risk of phenoconversion in RBD.

The aim of our study was to find out the opinion of patients with Parkinson's Disease (PD) whose disease was preceded by REM sleep behaviour disorder (RBD) regarding early information about the high risk of phenoconversion in RBD. RBD is an early clinical manifestation of α-synucleinopathies with a more than 90% risk of phenoconversion to PD, dementia with Lewy bodies (DLB) or multiple system atrophy (MSA). It remains a subject for debate as to whether and how RBD patients should be informed about the high risk of phenoconversion. The patient's right to full knowledge regarding his or her health conflicts with the potentially destructive impact of this information on his or her mental state and quality of life of them and their relatives. Thirty-nine patients with PD whose disease was preceded by RBD were surveyed. Data on the course of RBD and PD was collected. Questions were asked about early information about the high risk of phenoconversion to patients with RBD and factors determining the opinion of the surveyed persons. The majority ( > 60%) of respondents gave a positive answer when asked whether patients should be informed about their high risk of developing PD once diagnosed with RBD. Only a few (7.7%) respondents believed that disclosing such information to the patient should be possible only after obtaining his or her consent. Respondents associated consent to information about the high risk of developing PD in people with RBD with high expectations of the healthcare system. We were unable to determine whether factors such as the gender of the subject, the clinical course of the PD, and the RBD duration had an impact on patients' opinions regarding disclosing knowledge about phenoconversion. Our study provides important information that should influence physicians' communication with patients with RBD, especially regarding how they communicate about the high risk of phenoconversion.

Serum Uric Acid as a Putative Biomarker in Prodromal Parkinson's Disease: Longitudinal Data from the PPMI Study.

The role of blood uric acid as a biomarker in symptomatic motor PD has been increasingly established in the literature. Our present study assessed the role of serum uric acid as a putative biomarker in a prodromal PD cohort [REM Sleep Behavior disorder (RBD) and Hyposmia] followed longitudinally. Longitudinal 5-year serum uric acid measurement data of 39 RBD patients and 26 Hyposmia patients with an abnormal DATSCAN imaging were downloaded from the Parkinson's Progression Markers Initiative database. These cohorts were compared with 423 de novo PD patients and 196 healthy controls enrolled in the same study. After adjusting for age, sex, body mass index, and concomitant disorders (hypertension/gout), baseline and longitudinal serum uric acid levels were higher in the RBD subgroup as compared to the established PD cohort (p = 0.004 and p = 0.001). (Baseline RBD 6.07±1.6 vs. Baseline PD 5.35±1.3 mg/dL and Year-5 RBD 5.7±1.3 vs. Year-5 PD 5.26±1.33). This was also true for longitudinal measurements in the Hyposmic subgroup (p = 0.008) (Baseline Hyposmic 5.7±1.6 vs. PD 5.35±1.3 mg/dL and Year-5 Hyposmic 5.58±1.6 vs. PD 5.26±1.33). Our results indicate that serum uric acid levels are higher in prodromal PD subjects with ongoing dopaminergic degeneration compared to those with manifest PD. These data indicate that the well-established decrease in the levels of serum uric acid occurs with the transition from prodromal to clinical PD. Whether the higher levels of serum uric acid observed in prodromal PD may provide protection against conversion to full-blown clinical PD will require further study.

Occipital hypometabolism is a risk factor for conversion to Parkinson’s disease in isolated REM sleep behaviour disorder

PurposeIsolated REM sleep behaviour disorder (iRBD) patients are at high risk of developing clinical syndromes of the α-synuclein spectrum. Progression markers are needed to determine the neurodegenerative changes and to predict their conversion. Brain imaging with 18F-FDG PET in iRBD is promising, but longitudinal studies are scarce. We investigated the regional brain changes in iRBD over time, related to phenoconversion.MethodsTwenty iRBD patients underwent two consecutive 18F-FDG PET brain scans and clinical assessments (3.7 ± 0.6 years apart). Seventeen patients also underwent 123I-MIBG and 123I-FP-CIT SPECT scans at baseline. Four subjects phenoconverted to Parkinson’s disease (PD) during follow-up. 18F-FDG PET scans were compared to controls with a voxel-wise single-subject procedure. The relationship between regional brain changes in metabolism and PD-related pattern scores (PDRP) was investigated.ResultsIndividual hypometabolism t-maps revealed three scenarios: (1) normal 18F-FDG PET scans at baseline and follow-up (N = 10); (2) normal scans at baseline but occipital or occipito-parietal hypometabolism at follow-up (N = 4); (3) occipital hypometabolism at baseline and follow-up (N = 6). All patients in the last group had pathological 123I-MIBG and 123I-FP-CIT SPECT. iRBD converters (N = 4) showed occipital hypometabolism at baseline (third scenario). At the group level, hypometabolism in the frontal and occipito-parietal regions and hypermetabolism in the cerebellum and limbic regions were progressive over time. PDRP z-scores increased over time (0.54 ± 0.36 per year). PDRP expression was driven by occipital hypometabolism and cerebellar hypermetabolism.ConclusionsOur results suggest that occipital hypometabolism at baseline in iRBD implies a short-term conversion to PD. This might help in stratification strategies for disease-modifying trials.

0900 A Community-based Survey of Personal Perspectives Regarding Prodromal Sleep Screening for Neurodegenerative Disorders

Abstract Introduction Sleep markers can assess prodromal risk for neurodegenerative disorders (NDD). In a recent study conducted by the Mayo Clinic, most isolated REM sleep behavior disorder patients preferred knowing about their risk for parkinsonism or dementia. In their email survey, patients indicated a strong preference for disclosure of prognostic NDD risk in order to spur family discussions and plan for the future. For this pilot study, the Mayo questions were modified in order to investigate the perspectives and preferences of community-based adults about potentially being at-risk of a NDD and how it might impact their lives. Methods A brief survey was administered to Rotary Club attendees prior to a presentation on sleep and neurodegenerative disease. Each question offered five responses: strongly disagree, disagree, neutral, agree, or strongly agree. Personal identifiers were not obtained. Thirty-four surveys were completed from approximately equal numbers of older men and women with estimated ages above 50 years. Personal information were not obtained (e.g., age and sex). Results When asked whether it was important to know their NDD risk given the fact that there are no known methods to prevent or cure the disease, most (83%) strongly agreed or agreed, while only 18% preferred not to know their NDD risk. The majority felt they would be more pessimistic about their future if identified as being at risk of NDD the (62% strongly agreed/agreed). Most believed their priorities and plans for living life would change (68% strongly agreed/agreed). Further, the vast majority felt that knowing NDD risk would help them plan for the future (89% strongly agreed/agreed), including planning for health resources and support (88% strongly agreed/agreed). Conclusion Eighty-three percent of those surveyed reported they would benefit from knowing if they were at risk of NDD, even though the majority would feel more pessimistic about their future. The vast majority (89%) responded that knowing their NDD risk would help them plan for the future. These results suggest that most community adults might be receptive to future sleep screening for NDD with results. Investigations are underway to confirm these findings in a broader community-based study. Support (if any) NIA-R44AG050326

0899 Use of Artificial Intelligence for Early Characterization of Patients with RBD/RWA

Abstract Introduction The prevalence of polysomnography (PSG) confirmed REM sleep behavior disorder (RBD) has been estimated at 0.68% of the general population, and that of probable RBD at 5.65%. Isolated RBD is considered a pre-clinical marker of neurodegeneration with strong predictive value. Large longitudinal cohort studies demonstrate 81–91% of idiopathic RBD patients, followed for ≥14-years, will develop a definite neurodegenerative disease or mild cognitive impairment. Furthermore, high prevalence of sleep apnea (SA) exists in patients with RBD/REM without atonia (RWA), which can confound analysis of EMG tone and arousal activity. We demonstrate predictive AI models for RBD/RWA in subjects with and without SA. Methods Patients with known RBD/RWA who underwent PSG were divided into sub-groups with (n=86, RBDSA) and without SA (n=19, RBDNSA). Patient demographics, PSG characteristics, and co-morbid conditions were reviewed. Random forest (RF) models of PSG indices and Deep Learning (DL) methods identified predictive characteristics of RBD/RWA, sensitivity and specificity for RBD/RWA detection were estimated, and feature importance analysis was performed. Results Subjects with RBDSA compared to RBDNSA demonstrated greater BMI, AHI, Arousals (ArI), and Periodic Limb Movements (PLMs). In a Parkinson’s disease subgroup (n=12, RBDPD) compared to non-Parkinson’s sub-group, sleep was more fragmented, showing higher WASO, ArI, and PLMs. RF modeling demonstrated sensitivity/specificity of 67%/96% for RBDNSA subjects, and 79%/52% for RBDSA. Feature importance analysis resulted in several top-features for RBDNSA: N3 time, TST, AHI, REM duration, and sleep latency, while different top-features were observed for RBDSA: ratio of leg events in REM vs. non-REM, TST, ratio of arousals in REM vs. non-REM, REM duration, and REM time. Conclusion AI approaches including RF models produced high specificity and moderate sensitivity for RBDNSA subjects. Observed specificity was lower for RBDSA patients. We hypothesize the performance difference attributable to similarity and additional complexity in sleep disturbance characteristics between RBD and SA. Broad implementation of AI methods show potential to expand early detection and diagnosis of RBD and associated neurodegenerative conditions through expanded analysis, and follow-up, including RWA spectrum patients that don’t meet clinical thresholds for diagnosable RBD. Support (if any) None

Cortical excitability in patients with REM sleep behavior disorder with abnormal TRODAT-1 SPECT scan: an insight into prodromal Parkinson's disease.

REM Sleep Behavior Disorder (RBD) has been highlighted to identify a patient with prodromal Parkinson's disease (PD). Although many studies focus on biomarkers to predict an RBD patient's evolution from prodromal PD to clinical PD, the neurophysiological perturbation of cortical excitability has not yet been well elucidated. Moreover, no study describes the difference between RBD with and without abnormal TRODAT-1 SPECT. By measuring the amplitude of motor evoked potentials (MEP), the cortical excitability changes after transcranial magnetic stimulation (TMS) were evaluated in 14 patients with RBD and eight healthy controls (HC). Seven of the 14 patients with RBD showed abnormal TRODAT-1 (TRA-RBD), and seven were normal (TRN-RBD). The tested parameters of cortical excitability include resting motor threshold (RMT), active motor threshold (AMT), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), contralateral silence period (CSP), and input-output recruitment curve. The RMT and AMT showed no difference among the three studied groups. There was only SICI at inter-stimuli-interval 3 ms revealing group differences. The TRA-RBD demonstrated significant differences to HC in these aspects: decreased SICI, increased ICF, shortening of CSP, and augmented MEP amplitude at 100% RMT. Moreover, the TRA-RBD had a smaller MEP facilitation ratio at 50% and 100% of maximal voluntary contraction when compared to TRN-RBD. The TRN-RBD did not present any difference to HC. We showed that TRA-RBD shared similar cortical excitability changes with clinical PD. These findings would provide further insight into the concept that RBD is the highly prevalent entity in prodromal PD.

Ikelos-RWA. Validation of an Automatic Tool to Quantify REM Sleep Without Atonia.

Study Objectives. To present and evaluate an automatic scoring algorithm for quantification of REM-sleep without atonia (RWA) in patients with REM-sleep behaviour disorder (RBD) based on a generally accepted, well-validated visual scoring method, ("Montreal" phasic and tonic) and a recently developed, concise scoring method (Ikelos-RWA). Methods. Video-polysomnographies of 20 RBD patients (68.2 ± 7.2 years) and 20 control patients with periodic limb movement disorder (65.9 ± 6.7 years) were retrospectively analysed. RWA was estimated from chin electromyogram during REM-sleep. Visual and automated RWA scorings were correlated, and agreement (a) and Cohen's Kappa (k) calculated for 1735 minutes of REM-sleep of the RBD patients. Discrimination performance was evaluated with receiver operating characteristic (ROC) analysis. The algorithm was then applied on the polysomnographies of a cohort of 232 RBD patients (total analysed REM-sleep: 17,219 minutes) and evaluated, while correlating the different output parameters. Results. Visual and computer-derived RWA scorings correlated significantly (tonic Montreal: rTM = 0.77; phasic Montreal: rPM = 0.78; Ikelos-RWA: rI = 0.97; all p < 0.001) and showed good to excellent Kappa coefficients (kTM = 0.71; kPM = 0.79; kI = 0.77). The ROC analysis showed high sensitivities (95%-100%) and specificities (84%-95%) at the optimal operation points, with area under the curve (AUC) of 0.98, indicating high discriminating capacity. The automatic RWA scorings of 232 patients correlated significantly (rTM{I} = 0.95; rPM{I} = 0.91, p < 0.0001). Conclusions. The presented algorithm is an easy-to-use and valid tool for automatic RWA scoring in patients with RBD and may prove effective for general use being publicly available.

Quantitative measurement of motor activity during sleep in isolated REM sleep behavior disorder patients using actigraphy before and after treatment with clonazepam.

We conducted a prospective study to quantify motor activity during sleep measured by actigraphy before and after 3 months of treatment with clonazepam in patients with video-polysomnography (vPSG) confirmed isolated rapid eye movement (REM) sleep behavior disorder (iRBD). The motor activity amount (MAA) and the motor activity block (MAB) during sleep were obtained from actigraphy. Then, we compared quantitative actigraphic measures with the results of the REM sleep behavior disorder questionnaire for the previous 3-month period (RBDQ-3M) and of the Clinical Global Impression-Improvement scale (CGI-I), and analyzed correlations between baseline vPSG measures and actigraphic measures. Twenty-three iRBD patients were included in the study. After medication treatment, large activity MAA dropped in 39% of patients, and the number of MABs decreased in 30% of patients when applying 50% reduction criteria. 52% of patients showed more than 50% improvement in either one. On the other hand, 43% of patients answered "much or very much improved" on the CGI-I, and RBDQ-3M was reduced by more than half in 35% of patients. However, there was no significant association between the subjective and objective measures. Phasic submental muscle activity during REM sleep was highly correlated with small activity MAA (Spearman's rho = 0.78, p < .001) while proximal and axial movements during REM sleep correlated with large activity MAA (rho = 0.47, p = .030 for proximal movements, rho = 0.47, p = .032 for axial movements). Our findings imply that quantifying motor activity during sleep using actigraphy can objectively assess therapeutic response in drug trials in patients with iRBD.

Characterization of attentional event-related potential from REM sleep behavior disorder patients based on explainable machine learning

Background and objectiveIdiopathic rapid eye movement sleep behavior disorder (iRBD) is a prodromal stage of neurodegeneration and is associated with cortical dysfunction. The purpose of this study was to investigate the spatiotemporal characteristics of cortical activities underlying impaired visuospatial attention in iRBD patients using an explainable machine-learning approach. MethodsAn algorithm based on a convolutional neural network (CNN) was devised to discriminate cortical current source activities of iRBD patients due to single-trial event-related potentials (ERPs), from those of normal controls. The ERPs from 16 iRBD patients and 19 age- and sex-matched normal controls were recorded while the subjects were performing visuospatial attentional task, and converted to two-dimensional images representing current source densities on flattened cortical surface. The CNN classifier was trained based on overall data, and then, a transfer learning approach was applied for the fine-tuning to each patient. ResultsThe trained classifier yielded high classification accuracy. The critical features for the classification were determined by layer-wise relevance propagation, so that the spatiotemporal characteristics of cortical activities that were most relevant to cognitive impairment in iRBD were revealed. ConclusionsThese results suggest that the recognized dysfunction in visuospatial attention of iRBD patients originates from neural activity impairment in relevant cortical regions and may contribute to the development of useful iRBD biomarkers based on neural activity.

REM Sleep Behavior Disorder -A Narrative Review

Approximately 43% of patients with REM sleep behavior disorder (RBD) will develop Parkinson's disease and 25% with Lewy body dementia. The long-term clinical trial of RBD patients showed over 90% risk of developing neurodegenerative diseases. REM sleep behavior disease is characterized by the enactment of dreams, involving complex motor functions. The disease is now considered a prodrome to Parkinson’s disease. In the future, it is recommended for researchers to investigate the potential of REM sleep without tension as a clinical indication of neurodegenerative diseases, for which physicians can rely on to detect diseases for early intervention and treatment.

Clinical and neuroimaging markers of neurodegeneration in first-degree relatives of patients with REM sleep behavior disorder with and without isolated rapid eye movement sleep without atonia: A case-control clinical and dopamine PET study

ObjectivesThe current study aimed to examine the neurodegenerative implication of isolated REM sleep without atonia (RSWA) among first-degree relatives of patients with REM sleep behaviour disorder (RBD). MethodsThis cross-sectional case-control study recruited three groups of subjects: First-degree relatives of RBD patients with isolated RSWA (n = 17), first-degree relatives of RBD patients without isolated RSWA (n = 18), and normal controls who did not have any RWSA and family history of RBD (n = 15). Prodromal Parkinson's Disease likelihood ratio by the updated MDS Research Criteria and striatal dopaminergic transmission function of the subjects as assessed by triple-tracer (18F-DOPA, 11C-Raclopride, and 18F-FDG) PET/CT scan were used as proxy markers of neurodegeneration. ResultsIn contrary to our hypothesis, the three groups did not differ in their pre- or post-striatal dopaminergic transmission function, and their Prodromal Parkinson's Disease likelihood ratio. However, they differed significantly in their frequency of a having first-degree relatives with Parkinson's disease or dementia of Lewy body (first-degree relativess with RSWA vs first degree relatives without RSWA vs normal controls = 58.8% vs 22.2% vs 0%, p = 0.001). ConclusionFDRs of RBD patients with isolated RSWA did not have increased neurodegenerative markers compared to FDRs of RBD patients without isolated RSWA and normal control, despite an paradoxical increase in frequency of Parkinson's disease or dementia of Lewy body among their family compared to FDRs of RBD patients without isolated RSWA. Further longitudinal follow-up study will be needed to ascertain their long-term prognosis.

Aberrant corticospinal tract characteristics in prodromal PD: A diffusion tensor imaging study

IntroductionParkinson’s disease (PD) is typically diagnosed when motor symptoms first occur. However, PD-related non-motor symptoms may appear several years before diagnosis. REM sleep behaviour disorder (RBD) and olfactory deficits (hyposmia) are risk factors, but they are not specific for predicting progression towards PD. Other PD-related markers, for example brain imaging markers, may help to identify preclinical PD in hyposmic RBD patients. Studies have reported abnormal structural characteristics in the corticospinal tract (CST) of PD patients, but it is unclear whether hyposmic RBD patients have similar abnormalities that may help to predict PD in these individuals. This study examined whether CST abnormalities may be a potential marker of PD risk by using diffusion tensor imaging (DTI) measures. MethodsTwenty hyposmic RBD patients, 31 PD patients, and 29 healthy controls (HCs) were studied. DTI data were collected on a 1.5 T MRI scanner and CST characteristics (FA, MD, AD, and RD) were evaluated using probabilistic tractography (with seed regions in the bilateral primary motor cortex and mediolateral cerebral peduncles). Olfactory function was assessed with the University of Pennsylvania Smell Identification Test (UPSIT). ResultsHyposmic RBD patients showed significantly higher mean diffusivity (MD) values of the right CST compared to HCs but did not differ from PD patients. PD patients showed a trend of higher MD values compared to HCs. ConclusionsAltered diffusivity in the CST seems to be associated with RBD. The combination of RBD, hyposmia, and CST alterations may be related to later development of PD with comorbid RBD.

Inaccurate self-report of olfactory dysfunction in REM Sleep Behaviour Disorder and implications for prognosis

IntroductionThe earliest stages of alpha-synucleinopathies are accompanied by non-specific prodromal symptoms such as diminished sense of smell, constipation and depression, as well as more specific prodromal conditions including REM Sleep Behaviour Disorder (RBD). While the majority of RBD patients will develop an alpha-synucleinopathy, one of the greatest clinical challenges is determining whether and when individual patients will phenoconvert. Clinical evaluation of a patient presenting with RBD should therefore include robust and objective assessments of known alpha-synucleinopathy prodromes. MethodsThis study compared olfactory function self-report measures with psychophysical ‘Sniffin’ Stick 16-item Identification’ test scores in Control (n = 19), RBD (n = 16) and PD (n = 17) participants. ResultsWe confirm that olfactory test scores are significantly diminished in RBD and PD groups compared to Controls (p < 0.001, One-Way ANOVA with Tukey-Kramer Post-Hoc, effect size = 0.401). However, RBD participants were only 56 % accurate when self-reporting olfactory dysfunction, hence markedly less likely to perceive or acknowledge their own hyposmia compared to Controls (p = 0.045, Fisher’s Exact Test, effect-size = 0.35). ConclusionWhen isolated RBD presents with hyposmia, there is an increased likelihood of phenoconversion to Parkinson’s Disease (PD) or Dementia with Lewy Bodies (DLB); unawareness of olfactory dysfunction in an individual with isolated RBD may therefore confound differential diagnosis and prognosis. Our results evidence the fallibility of olfactory function self-report in the context of RBD prognosis, indicating that clinical assessments of RBD patients should include more reliable measures of olfactory status.

Quantitative Susceptibility Mapping and Free Water Imaging of Substantia Nigra in Parkinson's Disease.

The utility of imaging methods to detect iron content in the substantia nigra pars compacta (SNc) and free water imaging in the posterior substantia nigra (pSN) has the potential to be imaging markers for the detection of Parkinson's disease (PD). This study aimed to compare the discriminative power of above methods, and whether the combination can improve the diagnostic potential of PD. Quantitative susceptibility mapping (QSM) and diffusion-weighted data were obtained from 41 healthy controls (HC), 37 patients with idiopathic REM sleep behavior disorder (RBD), and 65 patients with PD. Mean QSM values of bilateral SNc and mean isotropic volume fraction (Viso) values of bilateral pSN (mean QSM|Viso values of bilateral SNc|pSN) were separately calculated and compared among the groups. Mean QSM|Viso values of bilateral SNc|pSN were significantly higher for RBD and PD patients compared to HC and were significantly higher in PD patients than in RBD patients. The power of the mean QSM|Viso values of bilateral SNc|pSN and combined mean QSM and Viso values was 0.873, 0.870, and 0.961 in discriminating PD and HC, 0.779, 0.719, and 0.864 in discriminating RBD from HC, 0.634, 0.636, and 0.689 in discriminating PD and RBD patients. QSM and free water imaging have similar discriminative power in the detection of prodromal and clinical PD, while combination of these two methods increases discriminative power. Our findings suggest that the combination of QSM and free water imaging has the potential to become an imaging marker for the diagnosis of PD.