Sleep Behavior Disorder Research Articles

Heart rate variability impairment during sleep in Veterans with REM sleep behavior disorder, traumatic brain injury, and posttraumatic stress disorder: An early potential window into autonomic dysfunction?

Comorbid REM sleep behavior disorder (RBD) and neurotrauma (NT, traumatic brain injury + post-traumatic stress disorder; RBD+NT) is associated with increased neurodegenerative symptom burden and worsened health. Sleep and autonomic function are integrally and bidirectionally related to neurodegenerative processes. In the current study, we sought to determine if early signs of autonomic dysfunction, measured via heart rate variability (HRV), were present during sleep in comorbid RBD+NT compared to RBD only and controls. Our data show reduced time and frequency domain HRV during NREM sleep in RBD+NT Veterans compared to RBD only and controls. These data contribute evidence that participants with RBD and comorbid NT demonstrate significantly worse autonomic dysfunction compared to age/sex matched participants with RBD alone.

CSF α-Synuclein Seed Amplification Assay in Patients With Atypical Parkinsonian Disorders.

There is no disease-modifying treatment of corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), 2 disorders characterized by their striking phenotypic, and, in CBS, pathologic heterogeneity. Seed amplification assays (SAAs) could enable the detection of neuropathologic processes, such as α-synuclein (αSyn) copathology, that affect the success of future disease-modifying treatment strategies. The primary objective was to assess possible αSyn copathology in CBS and PSP, as detected in CSF using an αSyn SAA (αSyn-SAA). Secondary objectives were to evaluate the association of αSyn-SAA positivity with other biomarkers including of Alzheimer disease (AD), and with clinical presentation. We hypothesized that αSyn-SAA positivity would be detectable in CBS and PSP and that it would be associated with AD biomarker positivity and β-amyloid (Aβ) 42 levels, neurodegeneration as assessed by neurofilament light chain (NfL) levels, and symptoms associated with synucleinopathies. This cross-sectional observational study included patients clinically diagnosed with CBS and PSP who underwent a lumbar puncture between 2012 and 2021 (Toronto Western Hospital, Canada). CSF was tested for αSyn-SAA positivity, AD biomarkers, and NfL levels. Clinical data were derived from medical records. We tested the CSF of 40 patients with CBS (19 female patients, 65.9 ± 8.6 years) and 28 with PSP (13 female patients, 72.5 ± 8.7 years old), mostly White (n = 50) or Asian (n = 14). αSyn-SAA positivity was observed in 35.9% patients with CBS and 28.6% with PSP. In young-onset, but not late-onset patients, αSyn-SAA positivity and AD positivity were associated (odds ratio [OR] 8.8, 95% CI 1.2-82.6, p < 0.05). A multivariable linear regression analysis showed a significant interaction of αSyn-SAA status by age at onset on CSF Aβ42 levels (β = 0.3 ± 0.1, p < 0.05). Indeed, age at onset was positively related to Aβ42 levels only in αSyn-SAA-positive patients, as shown by slope comparison. A logistic regression analysis also suggested that REM sleep behavior disorder was associated with αSyn-SAA positivity (OR 60.2, 95% CI 5.2-1,965.8; p < 0.01). We detected a frequency of αSyn-SAA positivity in CBS and PSP in line with pathologic studies, highlighting the usefulness of SAAs for in vivo detection of otherwise undetectable neuropathologic processes. Our results also suggest that AD status (specifically low Aβ42) and older age at onset may contribute to αSyn-SAA positivity. This opens new perspectives for the stratification of patients in clinical trials.

α-Synuclein species in plasma neuron-derived extracellular vesicles as biomarkers for iRBD.

Isolated REM sleep behavior disorder (iRBD) is considered as the strongest predictor of Parkinson's disease (PD). Reliable and accurate biomarkers for iRBD detection and the prediction of phenoconversion are in urgent need. This study aimed to investigate whether α-Synuclein (α-Syn) species in plasma neuron-derived extracellular vesicles (NDEVs) could differentiate between iRBD patients and healthy controls (HCs). Nanoscale flow cytometry was used to detect α-Syn-containing NDEVs in plasma. A total of 54 iRBD patients and 53 HCs were recruited. The concentrations of total α-Syn, α-Syn aggregates, and phosphorylated α-Syn at Ser129 (pS129)-containing NDEVs in plasma of iRBD individuals were significantly higher than those in HCs (p < 0.0001 for all). In distinguishing between iRBD and HCs, the area under the receiver operating characteristic (ROC) curve (AUC) for an integrative model incorporating the levels of α-Syn, pS129, and α-Syn aggregate-containing NDEVs in plasma was 0.965. This model achieved a sensitivity of 94.3% and a specificity of 88.9%. In iRBD group, the concentrations of α-Syn aggregate-containing NDEVs exhibited a negative correlation with Sniffin' Sticks olfactory scores (r = -0.351, p = 0.039). Smokers with iRBD exhibited lower levels of α-Syn aggregates and pS129-containing NDEVs in plasma compared to nonsmokers (pα-Syn aggregates = 0.014; ppS129 = 0.003). The current study demonstrated that the levels of total α-Syn, α-Syn aggregates, and pS129-containing NDEVs in the plasma of individuals with iRBD were significantly higher compared to HCs. The levels of α-Syn species-containing NDEVs in plasma may serve as biomarkers for iRBD.

Contribution of basal ganglia activity to REM sleep disorder in Parkinson’s disease

BackgroundRapid eye movement (REM) sleep behaviour disorder (RBD) is one of the most common sleep problems and represents a key prodromal marker in Parkinson’s disease (PD). It remains unclear whether...

Increased sighing during sleep as a marker of multiple system atrophy

Parkinson’s disease (PD) and multiple system atrophy (MSA) can be preceded by isolated REM sleep behavior disorder (iRBD). As excessive sighing during wakefulness is a red flag for MSA in individuals with parkinsonism, we measured sighing during slow wave sleep (N3) and REM sleep as potential biomarkers in 73 participants with MSA, 111 with iRBD, 257 with PD, and 115 controls. The number of sighs/hour of N3 (index) was higher in the MSA group than in the other groups. Sighs were rarer in REM sleep than in N3 sleep. A sigh index greater than 3.4/h of N3 was 95% sensitive in discriminating participants with MSA from controls, and a sigh index greater than 0.8 sigh/h of REM sleep was 87% specific in discriminating participants with MSA from controls. MSA participants with (vs. without) sigh were younger, had a lower apnea-hypopnea index (but no more stridor), and had no other difference in motor, autonomic, cognitive, and sensory symptoms. The sigh index could be used for screening for MSA in the millions of middle-aged persons who receive polysomnography for other purposes. Whether sighing in iRBD predicts preferential conversion towards MSA should be measured in a longitudinal study.

Research Progress on the Relationship between Parkinson's Disease and REM Sleep Behavior Disorder.

An individual's quality of life is greatly affected by Parkinson's disease (PD), a prevalent neurological degenerative condition. Rapid eye movement (REM) sleep behavior disorder (RBD) is a prominent non-motor symptom commonly associated with PD. Previous studies have shown a close relationship between PD and RBD. In addition to being a prodromal symptom of PD, RBD has a major negative impact on the prognosis of PD patients. This intrinsic connection indicates that there is a bidirectional relationship between PD and RBD. This paper provides a comprehensive review of the pathological mechanism related to PD and RBD, including the α-synuclein pathological deposition, abnormal iron metabolism, neuroinflammation, glymphatic system dysfunction and dysbiosis of the gut microbiota. Increasing evidence has shown that RBD patients have the same pathogenic mechanisms that underlie PD, but relatively little research has been done on how RBD contributes to PD progression. Therefore, a more thorough investigation is warranted to characterise how RBD affects the course of PD, in order to prepare for future therapeutic trials.

Orthostatic Hypotension: a clinical marker for the body-first subtype of patients with Parkinson’s Disease

Our study aimed to investigate the clinical characteristics of PD patients stratified by OH status before and after levodopa challenge to explore the hypothesis that OH might serve as a clinical marker for the body-first subtype of PD. Supine and standing blood pressure were measured in a large cross-sectional cohort of PD patients at the OFF status before and after levodopa challenge test (LCT). Based on OH status, patients were divided into three groups: spontaneous OH (SOH), only levodopa-induced OH (LOH) and non-OH (NOH). Clinical characteristics and associated factors were compared among the groups. A total of 928 patients with a mean age of 62.4 years and average disease duration of 7.9 years were included. There were 224 (24.1%) patients with SOH, 321 (34.6%) with LOH, and 383 (41.3%) with NOH. Compared to NOH, both SOH and LOH were associated with older age, motor fluctuations, and probable rapid eye movement sleep behavior disorder (pRBD). In addition, OH was more associated with cardiovascular and digestive dysfunction, disease severity and worse quality of life. Results of the current study suggest that PD patients developed OH which is more likely to comorbid with RBD, severe autonomic dysfunction and motor fluctuations, consistent with the body-first subtype of PD.

REM sleep without atonia and neurocognitive function in isolated REM sleep behaviour disorder: Cross-sectional and longitudinal study.

This study investigated the relationship between rapid eye movement sleep without atonia and cognitive profiles in individuals diagnosed with isolated rapid eye movement sleep behaviour disorder, assesssing both cross-sectional associations and their link to phenoconversion in a longitudinal follow-up. Participants underwent video-polysomnography, neurological examination, neuropsychological tests and structured interviews to confirm isolated rapid eye movement sleep behaviour disorder. Rapid eye movement sleep without atonia was manually scored using the Montreal method, and participants were categorized into either high or low electromyography activity groups, based on their tonic and phasic electromyography activities. The cross-sectional study included 250 patients with isolated rapid eye movement sleep behaviour disorder, revealing that those with high tonic electromyography activity exhibited significantly lower scores in the constructional praxis recall than those with low tonic electromyography activity (p = 0.002). In the longitudinal study, 79 participants (63 isolated rapid eye movement sleep behaviour disorder and 16 phenoconversion), tracked for at least 5 years, demonstrated that high tonic electromyography activity (odds ratio: 6.14; 95% confidence interval: 1.23-30.60; p = 0.027) and lower performance on the Trail Making Test A (odds ratio: 0.23; 95% confidence interval: 0.11-0.70; p = 0.007) were associated with future phenoconversion. These results confirm the link between tonic electromyography activity and neurodegeneration in isolated rapid eye movement sleep behaviour disorder. Combining rapid eye movement sleep without atonia assessment with cognitive evaluation could serve as an early predictive marker for phenoconversion in clinical settings.

Causal Associations between Tea Consumption and Rapid Eye Movement Sleep Behavior Disorder: A Mendelian Randomization Study

Introduction: Previous studies have shown that tea consumption may have a protective effect against neurodegenerative diseases. However, the exact causal relationship between tea consumption and the precursor stages of certain neurodegenerative diseases, namely, REM sleep behavior disorder (RBD), remains unclear. To evaluate the causal association between tea consumption and RBD, we employed a Mendelian randomization study. Methods: We identified genetic instrumental variables that are significantly associated with tea consumption through genome-wide association studies (GWAS) in European populations. Bidirectional two-sample Mendelian randomization was utilized to determine the causal relationship between tea consumption and RBD, while sensitivity analyses were further employed to evaluate the robustness of the results. The multivariate Mendelian randomization method was used to assess the influence of relevant confounding factors on the results. Results: In the MR analysis using the inverse-variance weighting method, a significant causal relationship between tea consumption and RBD was observed (OR = 0.046, 95% CI: 0.004–0.563, p = 0.016). The consistency of findings across maximum likelihood, MR Pleiotropy RESidual Sum and Outlier, and multivariate MR after adjusting for potential confounding further supports this causal association. Sensitivity analyses revealed no evidence of heterogeneity or pleiotropy. Conclusions: The findings of our study demonstrate a robust causal association between tea consumption and RBD, indicating that tea consumption may serve as a protective factor against the development of RBD.

Parkinson’s disease is associated with clonal hematopoiesis with TET2 mutation

Clonal hematopoiesis of indeterminate potential (CHIP), a premalignant expansion of mutated hematopoietic stem cells, is linked to immune alterations. Given the role of neuroinflammation and immune dysfunction in Parkinson’s disease (PD), we hypothesized a connection between CHIP and PD. We analyzed peripheral blood DNA from 341 PD, 92 isolated REM sleep behavior disorder (iRBD) patients, and 5003 controls using targeted sequencing of 24 genes associated with hematologic neoplasms. PD cases were classified by clinical progression mode: fast, slow, and typical. Using multivariable logistic regression models, CHIP prevalence was assessed against controls with a 1.0% variant allele fraction threshold. CHIP with TET2 mutations was more prevalent in PD than controls (aOR 1.75, 95% CI 1.11–2.77, p = 0.017), particularly in the fast motor progression subgroup (aOR 3.19, p = 0.004). No distinct associations were observed with iRBD. PD is linked to increased odds of CHIP with TET2 mutations, suggesting immune dysregulation in PD pathophysiology.

Blunted tachycardia and cardiac sympathetic denervation in isolated rapid eye movement sleep behavior disorder

BackgroundIsolated rapid eye movement sleep behavior disorder (iRBD) serves as a prodromal phase of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Blunted tachycardia (BT) during postural changes indicates neurogenic orthostatic hypotension, a marker of autonomic dysfunction. We aimed to investigate whether BT is associated with cardiac sympathetic neurogenic denervation. Additionally, we conducted a preliminary short-term follow-up to examine the potential prognostic significance of BT regarding phenoconversion and mortality.MethodsForty-three patients with iRBD at Shiga University of Medical Science Hospital underwent active standing tests to identify BT, defined by a specific ratio of decrease in systolic blood pressure to inadequate increase in heart rate after standing, and orthostatic hypotension. 123I-metaiodobenzylguanidine myocardial scintigraphy (123I-MIBG) and dopamine transporter single-photon emission computed tomography (DAT-SPECT) were performed. Participants were followed up for 3.4 ± 2.4 years for phenoconversion and 4.0 ± 2.3 years for mortality assessment, and the risk of events was analyzed using log-rank tests.ResultsAmong the 43 participants (mean age, 72.3 ± 7.9 years; 8 female), 17 met the BT criteria. We found no significant comorbidity-related differences in hypertension or diabetes between the BT(+) and BT(-) groups. Orthostatic hypotension was more prevalent in the BT(+) group than in the BT(-) group (47.1% vs 7.7%, p = 0.003). BT(+) patients were older with a lower early and delayed MIBG uptake; however, no significant differences were observed in DAT accumulation. Phenoconversion was observed in seven (41.2%) BT(+) and seven (26.9%) BT(-) patients. Three deaths were recorded in the BT(+) group (17.6%) and three in the BT(-) group (11.5%). No significant differences were observed in the risk of phenoconversion or mortality between the groups.ConclusionsWe have identified the possibility that BT reflects cardiac sympathetic neurogenic denervation in patients with iRBD. Future research is needed to elucidate the potential prognostic value of BT.

Psychopathology in Infants, Toddlers, and Preschool Children with Nonsyndromic Clefts of the Lip and/or Palate: A Case-Control Study.

The aim of this study is to assess psychopathology and maternal interactions in infants, toddlers, and preschool children with nonsyndromic clefts of the lip and/or palate (NSCLP) and association of psychopathology with cleft-related factors and maternal interactions. Twenty-six children from 4 to 72 months of age with NSCLP, who were attending the Plastic, Reconstructive and Aesthetic Surgery Department were included as the case group. Fifty-two healthy children who were matched on age and sex with the case group were taken as controls. Children were assessed in aspects of psychiatric diagnosis, articulation, and development. Speech and language disorders (SLD) (P<0.001), disorders of affect (DA) (P=0.005), feeding behavior disorder (P=0.002), sleep-behavior disorder (SBD) (P=0.038), and disordered mother-child relationship (P<0.001) were more prevalent in children with NSCLP. Dental alignment (P=0.024), number of operations (P=0.006), and type of operations (P=0.012) were associated with DA. The children in the case group, who had disordered relationship with their mothers had significantly more SLD (P=0.036) and SBD (P=0.039). Children with NSCLP are at risk of developing psychopathology, especially SLD and DA. Maternal interactions and the above cleft-related factors and may be the target of interventions to prevent and treat psychiatric disorders in these children.

Acetyl-DL-leucine in two individuals with REM sleep behavior disorder improves symptoms, reverses loss of striatal dopamine-transporter binding and stabilizes pathological metabolic brain pattern—case reports

Isolated REM Sleep Behavior Disorder (iRBD) is considered a prodrome of Parkinson’s disease (PD). We investigate whether the potentially disease-modifying compound acetyl-DL-leucine (ADLL; 5 g/d) has an effect on prodromal PD progression in 2 iRBD-patients. Outcome parameters are RBD-severity sum-score (RBD-SS-3), dopamine-transporter single-photon emission computerized tomography (DAT-SPECT) and metabolic “Parkinson-Disease-related-Pattern (PDRP)”-z-score in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). After 3 weeks ADLL-treatment, the RBD-SS-3 drops markedly in both patients and remains reduced for >18 months of ADLL-treatment. In patient 1 (female), the DAT-SPECT putaminal binding ratio (PBR) decreases in the 5 years pretreatment from normal (1.88) to pathological (1.22) and the patient’s FDG-PET-PDRP-z-score rises from 1.72 to 3.28 (pathological). After 22 months of ADLL-treatment, the DAT-SPECT-PBR increases to 1.67 and the FDG-PET-PDRP-z-score stabilizes at 3.18. Similar results are seen in patient 2 (male): his DAT-SPECT-PBR rises from a pretreatment value of 1.42 to 1.72 (close to normal) and the FDG-PET-PDRP-z-score decreases from 1.02 to 0.30 after 18 months of ADLL-treatment. These results support exploration of whether ADLL may have disease-modifying properties in prodromal PD.

Severe Sleep Disturbances in Persons With Dementia With REM Sleep Behavior Disorder and Family Caregivers: A Mixed Methods Study.

Coexisting dementia and rapid eye movement sleep behavior disorder (RBD) can negatively impact persons with dementia (PWD) and their family caregivers. Little research has investigated the relationship of sleep disturbance (i.e., RBD) in PWD-caregiver dyads who live together. Thus, we aimed to examine the impact of RBD symptoms on sleep quality of PWD and their family caregivers and describe sleep interrelationships. This mixed methods study analyzed qualitative and quantitative data (wearable devices, semi-structured interviews, sleep diaries, and sleep quality surveys). Two dyads' sleep parameters and sleep experiences are reported. Findings demonstrated that RBD symptoms in PWD affected sleep quality negatively (frequent awakening during the night and shortened deep sleep). Current findings highlight the importance of RBD assessment and management for PWD, as it could help improve caregivers' and PWDs' sleep quality and well-being. [Research in Gerontological Nursing, 17(5), 247-255.].

Outcomes of surgery for inflammatory bowel disease among patients with psychiatric disorders

BackgroundPsychiatric disorders (PDs) are common among patients with inflammatory bowel disease (IBD). Brain-gut dysfunction and psychotropic medications may have adverse effects on postoperative outcomes in patients with IBD. This study aimed to evaluate the association between PD and outcomes after surgery for IBD. MethodsThis was a retrospective study of adult patients with IBD who underwent small bowel, colon, or rectal resection in the 2016 to 2021 Nationwide Readmissions Database. PDs, including psychotic, mood, anxiety, eating, sleep, personality, and childhood-onset behavioral disorders, were identified. Records about colorectal cancer were excluded. Multivariate regressions were used to examine the association of PD with outcomes. ResultsOf 81,955 patients included in the study, 21,800 (26.6%) had PDs. On risk adjustment, PD was associated with significantly increased postoperative ileus (adjusted odds ratio [AOR], 1.11; 95% CI, 1.03–1.19), length of stay (β, +1.4 days; 95% CI, 1.1–1.7), and costs (β, +$2100; 95% CI, $1200-$3100) compared with no PD. In addition, patients with PDs experienced increased odds of nonhome discharge (AOR, 1.23; 95% CI, 1.12–1.34) and 30-day readmission (AOR, 1.32; 95% CI, 1.22–1.43). Over the study period, the prevalence of PDs significantly increased from 24.3% to 28.5% (P < .001), along with an increase in the rates of ileus among patients with PDs (8.1%−15.8%; P < .001). ConclusionPD is associated with a significantly greater burden of adverse clinical and financial outcomes after IBD operations. Given the growing prevalence of mental health conditions among patients with IBD, further efforts to optimize preoperative psychiatric care may enhance the quality of colorectal surgery.

REM and NREM Sleep Parasomnia in Anti-NMDA Receptor Encephalitis.

Encephalitis with anti-N-methyl-d-aspartate receptor antibodies (anti-NMDARe) is a rare disorder characterized by cognitive impairment, psychosis, seizures, and abnormal movements. Abnormal behaviors during REM sleep have not been described in anti-NMDARe. Patients were monitored by video-polysomnography on a first night followed by multiple sleep latency tests and 18 hours of bed rest. Two patients with anti-NMDARe developed during the acute and postacute phase parasomnias including REM sleep behavior disorder and continuous finalistic quiet gesturing during a mixed N2/R sleep. The parasomnia disorder was improved by gabapentin and clonazepam. Video-polysomnography avoids misdiagnosing these parasomnia behaviors for seizure or movement disorders and allows adequate treatment.

Difference in gut microbial dysbiotic patterns between body-first and brain-first Parkinson's disease

BackgroundThis study aims to identify distinct microbial and functional biomarkers characteristic of body-first or brain-first subtypes of Parkinson's disease (PD). This could illuminate the unique pathogenic mechanisms within these subtypes. MethodsIn this cross-sectional study, we classified 36 well-characterized PD patients into body-first, brain-first, or undetermined subtypes based on the presence of premotor REM sleep behavior disorder (RBD) and cardiac meta-iodobenzylguanidine (MIBG) uptake. We then conducted an in-depth shotgun metagenomic analysis of the gut microbiome for each subtype and compared the results with those from age- and sex-matched healthy controls. ResultsSignificant differences were found in the gut microbiome of body-first PD patients (n = 15) compared to both brain-first PD patients (n = 9) and healthy controls. The gut microbiome in body-first PD showed a distinct profile, characterized by an increased presence of Escherichia coli and Akkermansia muciniphila, and a decreased abundance of short-chain fatty acid-producing commensal bacteria. These shifts were accompanied by a higher abundance of microbial genes associated with curli protein biosynthesis and a lower abundance of genes involved in putrescine and spermidine biosynthesis. Furthermore, the combined use of premotor RBD and MIBG criteria was more strongly correlated with these microbiome differences than the use of each criterion independently. ConclusionsOur findings highlight the significant role of dysbiotic and pathogenic gut microbial alterations in body-first PD, supporting the body-first versus brain-first hypothesis. These insights not only reinforce the gut microbiome's potential as a therapeutic target in PD but also suggest the possibility of developing subtype-specific treatment strategies.

Machine Learning Predicts Phenoconversion from Polysomnography in Isolated REM Sleep Behavior Disorder.

Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of alpha-synucleinopathies. This study aimed at developing a fully-automated machine learning framework for the prediction of phenoconversion in patients with iRBD by using data recorded during polysomnography (PSG). A total of 66 patients with iRBD were included, of whom 18 converted to an overt alpha-synucleinopathy within 2.7 ± 1.0 years. For each patient, a baseline PSG was available. Sleep stages were scored automatically, and time and frequency domain features were derived from electromyography (EMG) and electroencephalography (EEG) signals in REM and non-REM sleep. Random survival forest was employed to predict the time to phenoconversion, using a four-fold cross-validation scheme and by testing several combinations of features. The best test performances were obtained when considering EEG features in REM sleep only (Harrel's C-index: 0.723 ± 0.113; Uno's C-index: 0.741 ± 0.11; integrated Brier score: 0.174 ± 0.06). Features describing EEG slowing had high importance for the machine learning model. This is the first study employing machine learning applied to PSG to predict phenoconversion in patients with iRBD. If confirmed in larger cohorts, these findings might contribute to improving the design of clinical trials for neuroprotective treatments.

Clinical assessment and striatal dopaminergic activity in healthy controls and patients with Parkinson's disease: a Bayesian approach.

We aimed to evaluate correlations between striatal dopamine transporter (DAT) uptake and clinical assessments in both patients with Parkinson's disease (PD) and healthy controls. This study enrolled 193 healthy controls, and 581 patients with PD. They underwent various clinical assessments and 123I-FP-CIT SPECT scans. After reconstruction, attenuation correction, and normalization of SPECT images, counts were measured from the bilateral caudate and putamen, and the occipital cortex for reference. Count densities for each region were extracted and used to calculate striatal binding ratios (SBRs) for each striatal region. SBR is calculated as (target region/reference region)-1. After logarithmic transformation of striatal SBRs, we analyzed the effects of clinical assessments on striatal SBRs using Bayesian hierarchical modeling. MDS-UPDRS total score, part I, part II, part III, Epworth Sleepiness Scale, REM sleep behavior disorder screening questionnaire, SCOPA-AUT total score were negatively associated with striatal SBR in patients with PD. Also, HVLT recognition discrimination was positively associated with striatal SBR in both healthy controls and patients with PD. In healthy control, MDS-UPDRS part II, MOCA, SCOPA-AUT total score were positively associated with striatal SBR. We demonstrated that motor symptom, sleep disturbance, autonomic symptom, and cognition of patients with PD were associated with striatal dopaminergic activity. In healthy controls, motor symptoms, autonomic symptom, and cognition were associated with striatal dopaminergic activity, some of which showing the opposite direction with patients with PD. This result might provide new insight to underlying mechanism of dopamine system with motor and non-motor assessments.

Clinical characteristics and phenoconversion in isolated REM sleep behavior disorder: a prospective single-center study in Korea, compared with Montreal cohort.

Isolated rapid-eye movement behavior disorder (iRBD) is a prodromal synucleinopathy, but its conversion rate and subtypes can vary among different cohorts. We report the clinical characteristics and phenoconversion rate of the large single-center iRBD cohort in Korea and compared it to the Montreal cohort. This prospective cohort study examined 238 patients with polysomnography confirmed iRBD from Seoul National University Hospital (SNUH) who completed at least one follow-up evaluation. We compared the baseline and phenoconversion data of the SNUH cohort to those of 242 iRBD patients in the Montreal cohort. In the SNUH cohort, age at RBD diagnosis was similar (66.4±7.8 vs 65.6±8.4, p=0.265), but the proportion of men was lower (63.0% vs. 74.0%, p=0.001), and the duration of follow-up was shorter than that in the Montreal cohort (3.7±2.0 vs. 4.8±3.6 years, p<0.001). During follow-up, 34 (11.8%) patients in the SNUH cohort converted to neurodegenerative disease: 18 (52.9%) to Parkinson's disease, 9 (26.5%) to dementia with Lewy bodies (DLB), and 7 (20.6%) to multiple system atrophy. The conversion rate in the SNUH cohort was 15% after 3 years, 22% after 5 years, and 32% after 7 years, which was significantly lower than that of the Montreal cohort (log-rank test, p=0.002). Among phenoconversion subtype, fewer subjects in the SNUH group than in the Montreal group converted to DLB (Gray's test p=0.001). Through a comparative analysis between the SNUH and Montreal cohorts, we identified a significant difference in phenoconversion rates, particularly for DLB patients. These findings underscore the importance of further research into the underlying factors, such as racial and geographical factors contributing to such disparities.