Gait Analysis and Magnetic Resonance Imaging Characteristics in Patients with Isolated Rapid Eye Movement Sleep Behavior Disorder.

BACKGROUND: Isolated rapid eye movement sleep behavioral disorder (iRBD) can precede neurodegenerative diseases. There is an urgent need for biomarkers to aid early intervention and neuroprotection. OBJECTIVE: The aim is to assess quantitative motor, cognitive, and brain magnetic resonance imaging (MRI) characteristics in iRBD patients. METHODS: Thirty-eight polysomnography-confirmed iRBD patients and 28 age- and sex-matched healthy controls underwent clinical, cognitive, and motor functional evaluations, along with brain MRI. Motor tasks included nine-hole peg test, five-times-sit-to-stand test, timed-up-and-go test, and 4-meter walking test with and without cognitive dual task. Quantitative spatiotemporal gait parameters were obtained using an optoelectronic system. Brain MRI analysis included functional connectivity (FC) of the main resting-state networks, gray matter (GM) volume using voxel-based morphometry, cortical thickness, and deep GM and brainstem volumes using FMRIB's Integrated Registration and Segmentation Tool and FreeSurfer. RESULTS: iRBD patients relative to healthy subjects exhibited a poorer performance during the nine-hole peg test and five-times-sit-to-stand test, and greater asymmetry of arm-swing amplitude and stride length variability during dual-task gait. Dual task significantly worsened the walking performance of iRBD patients more than healthy controls. iRBD patients exhibited nonmotor symptoms, and memory, abstract reasoning, and visuospatial deficits. iRBD patients exhibited decreased FC of pallidum and putamen within the basal ganglia network and occipital and temporal areas within the visuo-associative network, and a reduced volume of the supramarginal gyrus. Brain functional alterations correlated with gait changes. CONCLUSIONS: Subtle motor and nonmotor alterations were identified in iRBD patients, alongside brain structural and functional MRI changes. These findings may represent early signs of neurodegeneration and contribute to the development of predictive models for progression to parkinsonism. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Prevalence and correlates of probable rapid eye movement sleep behavior disorder among middle-aged and older adults in a psychiatric outpatient clinic: A cross-sectional survey.

OBJECTIVE: Rapid eye movement sleep behavior disorder (RBD) is often underdiagnosed among people living with mental disorders. The present study aimed to investigate the prevalence of probable RBD (pRBD) and its associated factors among middle-aged and older adults in a psychiatric outpatient clinic. METHODS: We conducted a cross-sectional survey among 2907 people aged 45-80 years who visited the outpatient clinic between March 1 and August 31, 2022 in a psychiatric hospital. A cutoff score ≥5 on the RBD Screening Questionnaire (RBDSQ) was used to indicate the presence of probable RBD (pRBD). Potential factors associated with pRBD were also assessed with a structured checklist. The association between these factors and the presence of pRBD was examined with logistic regression. RESULTS: The response rate was 64.3 %. Among 1868 respondents [age 58.5 ± 9.6 years, male n = 738 (39.5 %), female n = 1130 (60.5 %)], 15.9 % (95 % CI 14.2-17.6 %) screened positive for pRBD. Occupational exposure to chemicals; positive family history of psychotic disorders; a late start of mental health care; a medical history of autonomic dysfunction; mood problems; and use of antidepressants, hypnotics, and acetylcholinesterase inhibitors were associated with an increased likelihood of having pRBD (P < 0.05 for all). CONCLUSION: pRBD is common among outpatients with mental disorders, especially in mental disorders due to neurological diseases and physical conditions, mood disorders and anxiety or somatoform disorders. The findings highlight the importance of identifying sleep behavior disorders among people living with mental disorders in clinical practice.

Association of body mass index with rapid eye movement sleep behavior disorder in Parkinson's disease.

Background: The association between body mass index (BMI) and rapid eye-movement (REM) sleep-related behavioral disorder (RBD) in Parkinson's disease (PD) remains unknown. Our study was to investigate the association of BMI with RBD in PD patients. Methods: In this cross-sectional study, a total of 1,115 PD participants were enrolled from Parkinson's Progression Markers Initiative (PPMI) database. BMI was calculated as weight divided by height squared. RBD was defined as the RBD questionnaire (RBDSQ) score with the cutoff of 5 or more assessed. Univariable and multivariable logistic regression models were performed to examine the associations between BMI and the prevalence of RBD. Non-linear correlations were explored with use of restricted cubic spline (RCS) analysis. And the inflection point was determined by the two-line piecewise linear models. Results: We identified 426 (38.2%) RBD. The proportion of underweight, normal, overweight and obese was 2.61, 36.59, 40.36, and 20.44%, respectively. In the multivariate logistic regression model with full adjustment for confounding variables, obese individuals had an odds ratio of 1.77 (95% confidence interval: 1.21 to 2.59) with RBD compared with those of normal weight. In the RCS models with three knots, BMI showed a non-linear association with RBD. The turning points of BMI estimated from piecewise linear models were of 28.16 kg/m2, 28.10 kg/m2, and 28.23 kg/m2 derived from univariable and multivariable adjusted logistic regression models. The effect modification by depression on the association between BMI and RBD in PD was also found in this study. Furthermore, the sensitivity analyses linked with cognition, education, and ethnic groups indicated the robustness of our results. Conclusion: The current study found a significant dose-response association between BMI and RBD with a depression-based difference in the impact of BMI on RBD in PD patients.

Serotonin transporter density in isolated rapid eye movement sleep behavioral disorder.

Background/objective: The serotoninergic nervous system is known to play a role in the maintenance of rapid eye movement (REM) sleep. Serotoninergic projections are known to be vulnerable in synucleinopathies. To date, positron emission tomography (PET) studies using serotonin-specific tracers have not been reported in isolated REM sleep behavior disorder (iRBD). Methods: We conducted a cross-sectional imaging study using serotonin transporter (SERT) 11C-3-amino-4-(2-dimethylaminomethyl-phenylsulfaryl)-benzonitrile (DASB) PET to identify differences in serotonin system integrity between 11 participants with iRBD and 16 older healthy controls. Results: Participants with iRBD showed lower DASB distribution volume ratios (DVRs) in the total neocortical mantle [1.13 (SD: 0.07) vs. 1.19 (SD: 0.06); t = 2.33, p = 0.028)], putamen [2.07 (SD: 0.19) vs. 2.25 (SD: 0.18); t = 2.55, p = 0.017], and insula [1.26 (SD: 0.11) vs. 1.39 (SD: 0.09); t = 3.58, p = 0.001]. Paradoxical increases relative to controls were seen in cerebellar hemispheres [0.98 (SD: 0.04) vs. 0.95 (SD: 0.02); t = 2.93, p = 0.007)]. No intergroup differences were seen in caudate, substantia nigra, or other brainstem regions with the exception of the dorsal mesencephalic raphe [3.08 (SD: 0.53) vs. 3.47 (SD: 0.48); t = 2.00, p = 0.056] that showed a non-significant trend toward lower values in iRBD. Conclusions: Insular, neocortical, and striatal serotoninergic terminal loss may be common in prodromal synucleinopathies before the onset of parkinsonism or dementia. Given our small sample size, these results should be interpreted as hypothesis-generating/exploratory in nature.

Prediction of Co-Occurrence of Lewy Body Disease with Alzheimer's Disease.

Identifying the coexistence of Lewy body (LB) pathology with Alzheimer's disease (AD) in clinical practice is important in the era of anti-amyloid-ß antibody therapy. However, few studies have predicted the presence of comorbid LB pathology with AD using indicative biomarkers of dementia with Lewy bodies or by collecting detailed clinical symptoms. We report the clinical progression of a 67-year-old patient diagnosed with AD who developed rapid eye movement sleep disorder-like symptoms and transient visual hallucinations 10 years after AD onset and was considered to have comorbid LB pathology based on imaging indicative biomarkers of dementia with Lewy bodies.

Static and dynamic brain morphological changes in isolated REM sleep behavior disorder compared to normal aging.

Objective/background: To assess whether cerebral structural alterations in isolated rapid eye movement sleep behavior disorder (iRBD) are progressive and differ from those of normal aging and whether they are related to clinical symptoms. Patients/methods: In a longitudinal study of 18 patients with iRBD (age, 66.1 ± 5.7 years; 13 males; follow-up, 1.6 ± 0.6 years) and 24 age-matched healthy controls (age, 67.0 ± 4.9 years; 12 males; follow-up, 2.0 ± 0.9 years), all participants underwent multiple extensive clinical examinations, neuropsychological tests, and magnetic resonance imaging at baseline and follow-up. Surface-based cortical reconstruction and automated subcortical structural segmentation were performed on T1-weighted images. We used mixed-effects models to examine the differences between the groups and the differences in anatomical changes over time. Results: None of the patients with iRBD demonstrated phenoconversion during the follow-up. Patients with iRBD had thinner cortices in the frontal, occipital, and temporal regions, and more caudate atrophy, compared to that in controls. In similar regions, group-by-age interaction analysis revealed that patients with iRBD demonstrated significantly slower decreases in cortical thickness and caudate volume with aging than that observed in controls. Patients with iRBD had lower scores on the Korean version of the Mini-Mental Status Examination (p = 0.037) and frontal and executive functions (p = 0.049) at baseline than those in controls; however, no significant group-by-age interaction was identified. Conclusion: Patients with iRBD show brain atrophy in the regions that are overlapped with the areas that have been documented to be affected in early stages of Parkinson's disease. Such atrophy in iRBD may not be progressive but may be slower than that in normal aging. Cognitive impairment in iRBD is not progressive.

MRI brain structural and functional networks changes in Parkinson disease with REM sleep behavior disorders.

Background: Rapid eye movement sleep behavior disorder (RBD) is common in individuals with Parkinson's disease (PD). In spite of that, the precise mechanism underlying the pathophysiology of RBD among PD remains unclear. Objective: The aim of the present study was to analyze gray matter volumes (GMVs) as well as the changes of functional connectivity (FC) among PD patients with RBD (PD-RBD) by employing a combination of voxel-based morphometry (VBM) and FC methods. Methods: A total of 65 PD patients and 21 healthy control (HC) subjects were included in this study. VBM analyses were performed on all subjects. Subsequently, regions with significant different GMVs between PD patients with and without RBD (PD-nRBD) were selected for further analysis of FC. Correlations between altered GMVs and FC values with RBD scores were also investigated. Additionally, receiver operating characteristic (ROC) curves were employed for the evaluation of the predictive value of GMVs and FC in identifying RBD in PD. Results: PD-RBD patients exhibited lower GMVs in the left middle temporal gyrus (MTG) and bilateral cuneus. Furthermore, we observed higher FC between the left MTG and the right postcentral gyrus (PoCG), as well as lower FC between the bilateral cuneus (CUN) and the right middle frontal gyrus (MFG) among PD-RBD patients in contrast with PD-nRBD patients. Moreover, the GMVs of MTG (extending to the right PoCG) was positively correlated with RBD severity [as measured by REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) score]. Conversely, the FC value between the bilateral CUN and the right MTG in PD-RBD patients was negatively correlated with RBDSQ score. Conclusion: This study revealed the presence replace with GMV and FC changes among PD-RBD patients, which were closely linked to the severity of RBD symptoms. Furthermore, the combination of basic clinical characteristics, GMVs and FC values effectively predicted RBD for individuals with PD.

Validation of electronic diagnostic codes for rapid eye movement sleep behavior disorder.

We investigated the accuracy of International Classification of Diseases (ICD) codes for the identification of Veterans with rapid eye movement (REM) sleep behavior disorder (RBD). The charts of 139 randomly sampled Veterans with ≥1 ICD-9 and ICD-10 code(s) for RBD were reviewed for documentation of a suspected, previous, or current diagnosis; clinical symptoms; and/or empiric treatments for this disorder. Notably, 71 (51.1%) of patients with RBD electronic diagnoses lacked polysomnography (PSG), and 29 (20.9%) had PSG reports without commentary on REM sleep without atonia (RSWA). Sleep centers are therefore encouraged to include a brief sentence in PSG report templates commenting on the presence/absence of RSWA.

Microstructural alterations of the hypothalamus in Parkinson's disease and probable REM sleep behavior disorder.

BACKGROUND: Whether there is hypothalamic degeneration in Parkinson's disease (PD) and its association with clinical symptoms and pathophysiological changes remains controversial. OBJECTIVES: We aimed to quantify microstructural changes in hypothalamus using a novel deep learning-based tool in patients with PD and those with probable rapid-eye-movement sleep behavior disorder (pRBD). We further assessed whether these microstructural changes associated with clinical symptoms and free thyroxine (FT4) levels. METHODS: This study included 186 PD, 67 pRBD, and 179 healthy controls. Multi-shell diffusion MRI were scanned and mean kurtosis (MK) in hypothalamic subunits were calculated. Participants were assessed using Unified Parkinson's Disease Rating Scale (UPDRS), RBD Questionnaire-Hong Kong (RBDQ-HK), Hamilton Depression Rating Scale (HAMD), and Activity of Daily Living (ADL) Scale. Additionally, a subgroup of PD (n = 31) underwent assessment of FT4. RESULTS: PD showed significant decreases of MK in anterior-superior (a-sHyp), anterior-inferior (a-iHyp), superior tubular (supTub), and inferior tubular hypothalamus when compared with healthy controls. Similarly, pRBD exhibited decreases of MK in a-iHyp and supTub. In PD group, MK in above four subunits were significantly correlated with UPDRS-I, HAMD, and ADL. Moreover, MK in a-iHyp and a-sHyp were significantly correlated with FT4 level. In pRBD group, correlations were observed between MK in a-iHyp and UPDRS-I. CONCLUSIONS: Our study reveals that microstructural changes in the hypothalamus are already significant at the early neurodegenerative stage. These changes are associated with emotional alterations, daily activity levels, and thyroid hormone levels.

Cortical Macro- and Microstructural Changes in Parkinson's Disease with Probable Rapid Eye Movement Sleep Behavior Disorder.

BACKGROUND: Evidence regarding cortical atrophy patterns in Parkinson's disease (PD) with probable rapid eye movement sleep behavior disorder (RBD) (PD-pRBD) remains scarce. Cortical mean diffusivity (cMD), as a novel imaging biomarker highly sensitive to detecting cortical microstructural changes in different neurodegenerative diseases, has not been investigated in PD-pRBD yet. OBJECTIVES: The aim was to investigate cMD as a sensitive measure to identify subtle cortical microstructural changes in PD-pRBD and its relationship with cortical thickness (CTh). METHODS: Twenty-two PD-pRBD, 31 PD without probable RBD (PD-nonpRBD), and 28 healthy controls (HC) were assessed using 3D T1-weighted and diffusion-weighted magnetic resonance imaging on a 3-T scanner and neuropsychological testing. Measures of cortical brain changes were obtained through cMD and CTh. Two-class group comparisons of a general linear model were performed (P < 0.05). Cohen's d effect size for both approaches was computed. RESULTS: PD-pRBD patients showed higher cMD than PD-nonpRBD patients in the left superior temporal, superior frontal, and precentral gyri, precuneus cortex, as well as in the right middle frontal and postcentral gyri and paracentral lobule (d > 0.8), whereas CTh did not detect significant differences. PD-pRBD patients also showed increased bilateral posterior cMD in comparison with HCs (d > 0.8). These results partially overlapped with CTh results (0.5 < d < 0.8). PD-nonpRBD patients showed no differences in cMD when compared with HCs but showed cortical thinning in the left fusiform gyrus and lateral occipital cortex bilaterally (d > 0.5). CONCLUSIONS: cMD may be more sensitive than CTh displaying significant cortico-structural differences between PD subgroups, indicating this imaging biomarker's utility in studying early cortical changes in PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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

INTRODUCTION: Idiopathic 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 METHODS: A 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. CONCLUSIONS: ASL-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.

Rapid Eye Movement Sleep Behavior Disorder: Management and Prognostic Counseling.

Management of rapid eye movement sleep behavior disorder (RBD) includes reducing injurious dream-enactment behaviors, risk of injury to self and bedpartner, and vivid or disruptive dreams and improving sleep quality and bedpartner sleep disruption. Safety precautions should be reviewed at each visit. Medications to reduce RBD symptoms such as melatonin, clonazepam, pramipexole, and rivastigmine should be considered for most patients. Isolated RBD confers a high lifetime risk of neurodegenerative diseases with a latency often spanning many years. A patient-centered shared decision-making approach to risk disclosure is recommended. Knowledge of the risk allows for life planning and participation in research.

Functional connectivity-based classification of rapid eye movement sleep behavior disorder.

BACKGROUND: Isolated rapid eye movement sleep behavior disorder (iRBD) is a clinically important parasomnia syndrome preceding α-synucleinopathies, thereby prompting us to develop methods for evaluating latent brain states in iRBD. Resting-state functional magnetic resonance imaging combined with a machine learning-based classification technology may help us achieve this purpose. METHODS: We developed a machine learning-based classifier using functional connectivity to classify 55 patients with iRBD and 97 healthy elderly controls (HC). Selecting 55 HCs randomly from the HC dataset 100 times, we conducted a classification of iRBD and HC for each sampling, using functional connectivity. Random forest ranked the importance of functional connectivity, which was subsequently used for classification with logistic regression and a support vector machine. We also conducted correlation analysis of the selected functional connectivity with subclinical variations in motor and non-motor functions in the iRBDs. RESULTS: Mean classification performance using logistic regression was 0.649 for accuracy, 0.659 for precision, 0.662 for recall, 0.645 for f1 score, and 0.707 for the area under the receiver operating characteristic curve (p < 0.001 for all). The result was similar in the support vector machine. The classifier used functional connectivity information from nine connectivities across the motor and somatosensory areas, parietal cortex, temporal cortex, thalamus, and cerebellum. Inter-individual variations in functional connectivity were correlated with the subclinical motor and non-motor symptoms of iRBD patients. CONCLUSIONS: Machine learning-based classifiers using functional connectivity may be useful to evaluate latent brain states in iRBD.

Characterization of de novo Dementia with Lewy Body with different duration of rapid eye movement sleep behavior disorder.

BACKGROUND: Cognitive disorder, parkinsonism, autonomic dysfunction (AuD) and rapid eye movement sleep behavior disorder (RBD) can occur prior to or simultaneously with Dementia with Lewy Body (DLB) onset. RBD is generally linked with progressive neurodegenerative traits. However, associations between RBD with DLB, RBD without DLB, and RBD duration effects on DLB symptoms remain unclear. OBJECTIVES: To examine DLB symptom frequency and subtypes in RBD, and explore the effects of different RBD onset times on symptoms in de novo DLB patients. METHODS: In this multicenter investigation, we consecutively recruited 271 de novo DLB patients. All had standardized clinical and comprehensive neuropsychological evaluations. Subgroup analyses, performed based on the duration of RBD confirmed by polysomnography before the DLB diagnosis, we compared the proportion of patients with cognitive impairment, parkinsonism, and AuD features between groups. RESULTS: Parkinsonism and AuD incidences were significantly elevated in DLB patients with RBD when compared with patients without RBD. Subgroup analyses indicated no significant differences in parkinsonism between DLB patients who developed RBD ≥10 years prior to the DLB diagnosis and DLB patients without RBD. The incidence of non-tremor-predominant parkinsonism and AuD was significantly higher in DLB patients whose RBD duration before the DLB diagnosis was <10 years when compared with DLB patients without RBD. CONCLUSIONS: We identified significant symptom and phenotypic variability between DLB patients with and without RBD. Also, different RBD duration effects before the DLB diagnosis had a significant impact on symptomatic phenotypes, suggesting the existence of a slowly progressive DLB neurodegenerative subtype.

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

OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: The changes in RME had a relationship with cognitive impairments, especially memory, in patients with iRBD.

Reduced Gastric Contraction in Rapid-Eye-Movement Sleep Behavior Disorder and De Novo Parkinson's Disease.

BACKGROUND: Reduced gastric motility in Parkinson's disease (PD) has been reported, but hardly any study exists in subjects with isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD), a specific prodrome of α-synucleinopathies. OBJECTIVES: We compared the gastric motility of 17 iRBD subjects with that of 18 PD subjects (15 drug naive, 3 early treated in defined off) and 15 healthy controls (HC) with real-time magnetic resonance imaging (rtMRI). METHODS: After overnight fasting, participants consumed a standardized breakfast and underwent a 3-T rtMRI of the stomach. Amplitude and velocity of the peristaltic waves were analyzed under blinded conditions. Gastric motility index (GMI) was calculated. The procedure was repeated in 12 of 17 iRBD subjects ~2.5 years later. Nine of these 12 iRBD subjects were hyposmic. RESULTS: In iRBD and PD subjects the amplitude of the peristaltic waves was significantly reduced compared with HCs (iRBD vs. HC: 8.7 ± 3.7 vs. 11.9 ± 4.1 mm, P = 0.0097; PD vs. HC: 6.8 ± 2.2 vs. 11.9 ± 4.1 mm, P = 0.0001). The amplitude in iRBD and PD subjects was decreased to the same extent. The GMI was reduced in only PD subjects (PD vs. HC: P = 0.0027; PD vs. iRBD: P = 0.0203). After ~2.5 years the amplitude in iRBD subjects did not significantly decrease further. CONCLUSION: The amplitude of the peristaltic waves was markedly reduced in iRBD, a prodrome of α-synucleinopathies. This reduction was similar to the extent observed already in manifest early PD. This finding implies that the α-synuclein pathology affects the innervation of the stomach already in the prodromal stage. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Therapeutic Effect of Gandou Decoction on Wilson's Disease with Dampness Heat Accumulation Accompanied by Rapid Eye Movement Sleep Behavior Disorder / 中国实验方剂学杂志

ObjectiveTo explore the clinical efficacy of Gandou decoction in treating Wilson's disease （WD） with dampness heat accumulation accompanied by rapid eye movement （REM） sleep behavior disorder （RBD）. MethodFrom April 2019 to August 2023，62 patients with dampness heat accumulation type WD accompanied by RBD who met the inclusion criteria were selected from the Department of Encephalopathy at the First Affiliated Hospital of Anhui University of Chinese Medicine. They were randomly divided into a control group and an observation group with 31 cases each using a computer distributor. The control group received routine copper removal treatment，while the observation group received additional treatment with Gandou decoction on the basis of the control group. Eight days was one course of treatment，totaling three courses. The scores of traditional Chinese medicine syndromes，RBD screening questionnaire （RBDSQ） scores，RBD questionnaire-Hong Kong （RBDQ-HK） scores，polysomnography （PSG） parameters，24-hour urine copper （24 h U-Cu） levels，and non-ceruloplasmin-bound copper （NCC） levels between the two groups before and after treatment were compared，and adverse reactions were observed. ResultSixty trial cases were ultimately completed，with 30 cases in each group. Before treatment，there was no statistically significant difference in various indicators between the two groups， and thus they were comparable. Compared with those before treatment，the traditional Chinese medicine syndrome scores，RBDSQ scores and RBDQ-HK scores of the two groups were significantly reduced，the 24 h U-Cu levels were significantly increased，and the NCC levels were significantly reduced （P<0.05，P<0.01）. Compared with the control group， the observation group showed better improvement in traditional Chinese medicine syndrome scores， RBDSQ scores， RBDQ-HK scores， and NCC levels （P<0.05，P<0.01）. Compared with those before treatment，the total sleep time （TST），sleep efficiency （SE），sleep/REM latency，the proportion of N1/N2/REM stages，arousal index （ARI），and proportion of phasic electromyographic activity （P-EMG-A） were significantly improved in both groups （P<0.05）. Compared with the control group after treatment，the observation group showed more significant improvements in the proportion of TST，SE，REM stages，ARI，and P-EMG-A proportion （P<0.05）. ConclusionGandou decoction can not only improve the traditional Chinese medicine syndrome of WD patients with dampness heat accumulation accompanied by RBD but also alleviate their RBD symptoms.

Clinical correlates of pareidolias and color discrimination deficits in idiopathic REM sleep behavior disorder and Parkinson's disease.

Visuoperceptual dysfunction is common in Parkinson's disease (PD) and is also reported in its prodromal phase, isolated REM sleep behavior disorder (iRBD). We aimed to investigate color discrimination ability and complex visual illusions known as pareidolias in patients with iRBD and PD compared to healthy controls, and their associating clinical factors. 46 iRBD, 43 PD, and 64 healthy controls performed the Farnsworth-Munsell 100 hue test and noise pareidolia tests. Any relationship between those two visual functions and associations with prodromal motor and non-motor manifestations were evaluated, including MDS-UPDRS part I to III, Cross-Cultural Smell Identification Test, sleep questionnaires, and comprehensive neuropsychological assessment. iRBD and PD patients both performed worse on the Farnsworth-Munsell 100 hue test and had greater number of pareidolias compared to healthy controls. No correlations were found between the extent of impaired color discrimination and pareidolia scores in either group. In iRBD patients, pareidolias were associated with frontal executive dysfunction, while impaired color discrimination was associated with visuospatial dysfunction, hyposmia, and higher MDS-UPDRS-III scores. Pareidolias in PD patients correlated with worse global cognition, whereas color discrimination deficits were associated with frontal executive dysfunction. Color discrimination deficits and pareidolias are frequent but does not correlate with each other from prodromal to clinically established stage of PD. The different pattern of clinical associates with the two visual symptoms suggests that evaluation of both color and pareidolias may aid in revealing the course of neurodegeneration in iRBD and PD patients.

Clinical features and neurobiochemical mechanisms of olfactory dysfunction in patients with Parkinson disease.

This study aimed to investigate clinical features, influencing factors and neurobiochemical mechanisms of olfactory dysfunction (OD) in Parkinson disease (PD). Total 39 patients were divided into the PD with OD (PD-OD) and PD with no OD (PD-nOD) groups according to overall olfactory function, including threshold, discrimination and identification, assessed by Sniffin' Sticks test. Motor function and non-motor symptoms were rated by multiple scales. Dopamine, acetylcholine, norepinephrine and 5-hydroxytryptamine levels in cerebrospinal fluid (CSF) were measured. We found that the PD-OD group showed significantly lower score of Montreal Cognitive Assessment Scale, higher scores of rapid eye movement sleep behavior disorder (RBD) Screening Questionnaire and Epworth Sleepiness Scale than the PD-nOD group (p < 0.05). RBD Screening Questionnaire score was independently associated with the scores of overall olfactory function and discrimination (p < 0.05). Dopamine and acetylcholine levels in CSF from the PD-OD group was significantly lower than that from the PD-nOD group (p < 0.05). Dopamine and acetylcholine levels in CSF were significantly and positively correlated with the scores of overall olfactory function, threshold, discrimination and identification in PD patients (p < 0.05). RBD Screening Questionnaire score was significantly and negatively correlated with acetylcholine level in CSF in PD patients with poor olfactory detection (p < 0.05). This investigation reveals that PD-OD is associated with cognitive impairment, probable RBD and excessive daytime sleepiness. PD-OD is correlated with the decreased levels of dopamine and acetylcholine in CSF. RBD is an independent influencing factor of overall olfactory function and discrimination, and the decreased acetylcholine level in CSF may be the common neurobiochemical basis of RBD and OD in PD patients.

Overnight Distribution of REM Sleep Features in People with Parkinson's Disease (PD) and Non-PD Controls.

BACKGROUND: Rapid eye movement (REM) sleep behavior disorder (RBD) is a leading predictor of Parkinson's disease (PD). Diagnosis is performed in the sleep laboratory by detecting pathological REM sleep without atonia (RSWA). The evidence on the overnight distribution of RSWA% is conflicting. OBJECTIVE: To investigate the temporal distribution of the number of ocular movements per REM sleep minute (REM density), and RSWA% in people with PD and non-PD controls. METHODS: All participants underwent a single overnight evaluation in a sleep laboratory. Clinical evaluation was performed on a separate day. REM density and RSWA% were compared between PD and controls both across four sleep periods and individual REM cycles. RESULTS: A total of 51 participants with recorded RSWA in polysomnography laboratory were included, 28 with PD aged 64±9 years with a disease duration of 3.3±2.9 years, and 23 controls aged 55±8 years. People with PD had lower REM density and higher RSWA% compared to controls. As expected, REM density was higher towards the morning. In contrast, RSWA% was equally distributed across the night, for both PD and controls. CONCLUSIONS: PD pathology affects REM sleep features, but not the overnight distribution of those features. While REM density increased towards the end of the night, RSWA% was equally distributed across the night for both PD and controls. Our findings have clinical implications for diagnosing RBD, as quantification of RSWA% in any sleep cycle is sufficient for reliably evaluating total RSWA% and reduced REM density may be a marker of PD.