REM Sleep Behavior Disorder Research Articles

Longitudinal evolution of cortical thickness signature reflecting Lewy body dementia in isolated REM sleep behavior disorder: a prospective cohort study

BackgroundThe isolated rapid-eye-movement sleep behavior disorder (iRBD) is a prodromal condition of Lewy body disease including Parkinson's disease and dementia with Lewy bodies (DLB). We aim to investigate the longitudinal evolution of DLB-related cortical thickness signature in a prospective iRBD cohort and evaluate the possible predictive value of the cortical signature index in predicting dementia-first phenoconversion in individuals with iRBD.MethodsWe enrolled 22 DLB patients, 44 healthy controls, and 50 video polysomnography-proven iRBD patients. Participants underwent 3-T magnetic resonance imaging (MRI) and clinical/neuropsychological evaluations. We characterized DLB-related whole-brain cortical thickness spatial covariance pattern (DLB-pattern) using scaled subprofile model of principal components analysis that best differentiated DLB patients from age-matched controls. We analyzed clinical and neuropsychological correlates of the DLB-pattern expression scores and the mean values of the whole-brain cortical thickness in DLB and iRBD patients. With repeated MRI data during the follow-up in our prospective iRBD cohort, we investigated the longitudinal evolution of the cortical thickness signature toward Lewy body dementia. Finally, we analyzed the potential predictive value of cortical thickness signature as a biomarker of phenoconversion in iRBD cohort.ResultsThe DLB-pattern was characterized by thinning of the temporal, orbitofrontal, and insular cortices and relative preservation of the precentral and inferior parietal cortices. The DLB-pattern expression scores correlated with attentional and frontal executive dysfunction (Trail Making Test-A and B: R = − 0.55, P = 0.024 and R = − 0.56, P = 0.036, respectively) as well as visuospatial impairment (Rey-figure copy test: R = − 0.54, P = 0.0047). The longitudinal trajectory of DLB-pattern revealed an increasing pattern above the cut-off in the dementia-first phenoconverters (Pearson’s correlation, R = 0.74, P = 6.8 × 10−4) but no significant change in parkinsonism-first phenoconverters (R = 0.0063, P = 0.98). The mean value of the whole-brain cortical thickness predicted phenoconversion in iRBD patients with hazard ratio of 9.33 [1.16–74.12]. The increase in DLB-pattern expression score discriminated dementia-first from parkinsonism-first phenoconversions with 88.2% accuracy.ConclusionCortical thickness signature can effectively reflect the longitudinal evolution of Lewy body dementia in the iRBD population. Replication studies would further validate the utility of this imaging marker in iRBD.

Spatiotemporal characteristics of cortical activities of REM sleep behavior disorder revealed by explainable machine learning using 3D convolutional neural network

Isolated rapid eye movement sleep behavior disorder (iRBD) is a sleep disorder characterized by dream enactment behavior without any neurological disease and is frequently accompanied by cognitive dysfunction. The purpose of this study was to reveal the spatiotemporal characteristics of abnormal cortical activities underlying cognitive dysfunction in patients with iRBD based on an explainable machine learning approach. A convolutional neural network (CNN) was trained to discriminate the cortical activities of patients with iRBD and normal controls based on three-dimensional input data representing spatiotemporal cortical activities during an attention task. The input nodes critical for classification were determined to reveal the spatiotemporal characteristics of the cortical activities that were most relevant to cognitive impairment in iRBD. The trained classifiers showed high classification accuracy, while the identified critical input nodes were in line with preliminary knowledge of cortical dysfunction associated with iRBD in terms of both spatial location and temporal epoch for relevant cortical information processing for visuospatial attention tasks.

β-Amyloid Load on PET Along the Continuum of Dementia With Lewy Bodies.

β-Amyloid (Aβ) plaques can co-occur with Lewy-related pathology in patients with dementia with Lewy bodies (DLB), but Aβ load at prodromal stages of DLB still needs to be elucidated. We investigated Aβ load on PET throughout the DLB continuum, from an early prodromal stage of isolated REM sleep behavior disorder (iRBD) to a stage of mild cognitive impairment with Lewy bodies (MCI-LB), and finally DLB. We performed a cross-sectional study in patients with a diagnosis of iRBD, MCI-LB, or DLB from the Mayo Clinic Alzheimer Disease Research Center. Aβ levels were measured by Pittsburgh compound B (PiB) PET, and global cortical standardized uptake value ratio (SUVR) was calculated. Global cortical PiB SUVR values from each clinical group were compared with each other and with those of cognitively unimpaired (CU) individuals (n = 100) balanced on age and sex using analysis of covariance. We used multiple linear regression testing for interaction to study the influences of sex and APOE ε4 status on PiB SUVR along the DLB continuum. Of the 162 patients, 16 had iRBD, 64 had MCI-LB, and 82 had DLB. Compared with CU individuals, global cortical PiB SUVR was higher in those with DLB (p < 0.001) and MCI-LB (p = 0.012). The DLB group included the highest proportion of Aβ-positive patients (60%), followed by MCI-LB (41%), iRBD (25%), and finally CU (19%). Global cortical PiB SUVR was higher in APOE ε4 carriers compared with that in APOE ε4 noncarriers in MCI-LB (p < 0.001) and DLB groups (p = 0.049). Women had higher PiB SUVR with older age compared with men across the DLB continuum (β estimate = 0.014, p = 0.02). In this cross-sectional study, levels of Aβ load was higher further along the DLB continuum. Whereas Aβ levels were comparable with those in CU individuals in iRBD, a significant elevation in Aβ levels was observed in the predementia stage of MCI-LB and in DLB. Specifically, APOE ε4 carriers had higher Aβ levels than APOE ε4 noncarriers, and women tended to have higher Aβ levels than men as they got older. These findings have important implications in targeting patients within the DLB continuum for clinical trials of disease-modifying therapies.

Oligomeric Alpha-Synuclein and STX-1A from Neural-Derived Extracellular Vesicles (NDEVs) as Possible Biomarkers of REM Sleep Behavior Disorder in Parkinson's Disease: A Preliminary Cohort Study.

REM sleep behavior disorder (RBD) has a tighter link with synucleinopathies than other neurodegenerative disorders. Parkinson's Disease (PD) patients with RBD have a more severe motor and cognitive impairment; biomarkers for RBD are currently unavailable. Synaptic accumulation of α-Syn oligomers and their interaction with SNARE proteins is responsible for synaptic dysfunction in PD. We verified whether oligomeric α-Syn and SNARE components in neural-derived extracellular vesicles (NDEVs) in serum could be biomarkers for RBD. Forty-seven PD patients were enrolled, and the RBD Screening Questionnaire (RBDSQ) was compiled. A cut-off score > 6 to define probable RBD (p-RBD) and probable non-RBD (p non-RBD) was used. NDEVs were isolated from serum by immunocapture, and oligomeric α-Syn and SNARE complex components VAMP-2 and STX-1 were measured by ELISA. NDEVs' STX-1A resulted in being decreased in p-RBD compared to p non-RBD PD patients. A positive correlation between NDEVs' oligomeric α-Syn and RBDSQ total score was found (p = 0.032). Regression analysis confirmed a significant association between NDEVs' oligomeric α-Syn concentration and RBD symptoms (p = 0.033) independent from age, disease duration, and motor impairment severity. Our findings suggest that synuclein-mediated neurodegeneration in PD-RBD is more diffuse. NDEVs' oligomeric α-Syn and SNARE complex components' serum concentrations could be regarded as reliable biomarkers for the RBD-specific PD endophenotype.

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.

Melatonin as a Chronobiotic/Cytoprotective Agent in REM Sleep Behavior Disorder.

Dream-enactment behavior that emerges during episodes of rapid eye movement (REM) sleep without muscle atonia is a parasomnia known as REM sleep behavior disorder (RBD). RBD constitutes a prodromal marker of α-synucleinopathies and serves as one of the best biomarkers available to predict diseases such as Parkinson disease, multiple system atrophy and dementia with Lewy bodies. Most patients showing RBD will convert to an α-synucleinopathy about 10 years after diagnosis. The diagnostic advantage of RBD relies on the prolonged prodromal time, its predictive power and the absence of disease-related treatments that could act as confounders. Therefore, patients with RBD are candidates for neuroprotection trials that delay or prevent conversion to a pathology with abnormal α-synuclein metabolism. The administration of melatonin in doses exhibiting a chronobiotic/hypnotic effect (less than 10 mg daily) is commonly used as a first line treatment (together with clonazepam) of RBD. At a higher dose, melatonin may also be an effective cytoprotector to halt α-synucleinopathy progression. However, allometric conversion doses derived from animal studies (in the 100 mg/day range) are rarely employed clinically regardless of the demonstrated absence of toxicity of melatonin in phase 1 pharmacological studies with doses up to 100 mg in normal volunteers. This review discusses the application of melatonin in RBD: (a) as a symptomatic treatment in RBD; (b) as a possible disease-modifying treatment in α-synucleinopathies. To what degree melatonin has therapeutic efficacy in the prevention of α-synucleinopathies awaits further investigation, in particular multicenter double-blind trials.

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.

Validation of the REM behaviour disorder phenoconversion-related pattern in an independent cohort

BackgroundA brain glucose metabolism pattern related to phenoconversion in patients with idiopathic/isolated REM sleep behaviour disorder (iRBDconvRP) was recently identified. However, the validation of the iRBDconvRP in an external, independent group of iRBD patients is needed to verify the reproducibility of such pattern, so to increase its importance in clinical and research settings. The aim of this work was to validate the iRBDconvRP in an independent group of iRBD patients.MethodsForty iRBD patients (70 ± 5.59 years, 19 females) underwent brain [18F]FDG-PET in Seoul National University. Thirteen patients phenoconverted at follow-up (7 Parkinson disease, 5 Dementia with Lewy bodies, 1 Multiple system atrophy; follow-up time 35 ± 20.56 months) and 27 patients were still free from parkinsonism/dementia after 62 ± 29.49 months from baseline. We applied the previously identified iRBDconvRP to validate its phenoconversion prediction power.ResultsThe iRBDconvRP significantly discriminated converters from non-converters iRBD patients (p = 0.016; Area under the Curve 0.74, Sensitivity 0.69, Specificity 0.78), and it significantly predicted phenoconversion (Hazard ratio 4.26, C.I.95%: 1.18–15.39).ConclusionsThe iRBDconvRP confirmed its robustness in predicting phenoconversion in an independent group of iRBD patients, suggesting its potential role as a stratification biomarker for disease-modifying trials.

Gut microbiome dysbiosis across early Parkinson’s disease, REM sleep behavior disorder and their first-degree relatives

The microbiota-gut-brain axis has been suggested to play an important role in Parkinson’s disease (PD). Here we performed a cross-sectional study to profile gut microbiota across early PD, REM sleep behavior disorder (RBD), first-degree relatives of RBD (RBD-FDR), and healthy controls, which could reflect the gut-brain staging model of PD. We show gut microbiota compositions are significantly altered in early PD and RBD compared with control and RBD-FDR. Depletion of butyrate-producing bacteria and enrichment of pro-inflammatory Collinsella have already emerged in RBD and RBD-FDR after controlling potential confounders including antidepressants, osmotic laxatives, and bowel movement frequency. Random forest modelling identifies 12 microbial markers that are effective to distinguish RBD from control. These findings suggest that PD-like gut dysbiosis occurs at the prodromal stages of PD when RBD develops and starts to emerge in the younger RBD-FDR subjects. The study will have etiological and diagnostic implications.

Considering REM Sleep Behavior Disorder in the Management of Parkinson's Disease.

Rapid eye movement (REM) sleep behavior disorder (RBD) is the result of the loss of physiological inhibition of muscle tone during REM sleep, characterized by dream-enacting behavior and widely recognized as a prodromal manifestation of alpha-synucleinopathies. Indeed, patients with isolated RBD (iRBD) have an extremely high estimated risk to develop a neurodegenerative disease after a long follow up. Nevertheless, in comparison with PD patients without RBD (PDnoRBD), the occurrence of RBD in the context of PD (PDRBD) seems to identify a unique, more malignant phenotype, characterized by a more severe burden of disease in terms of both motor and non-motor symptoms and increased risk for cognitive decline. However, while some medications (eg, melatonin, clonazepam, etc.) and non-pharmacological options have been found to have some therapeutic benefits on RBD there is no available treatment able to modify the disease course or, at least, slow down the neurodegenerative process underlying phenoconversion. In this scenario, the long prodromal phase may allow an early therapeutic window and, therefore, the identification of multimodal biomarkers of disease onset and progression is becoming increasingly crucial. To date, several clinical (motor, cognitive, olfactory, visual, and autonomic features) neurophysiological, neuroimaging, biological (biofluids or tissue biopsy), and genetic biomarkers have been identified and proposed, also in combination, as possible diagnostic or prognostic markers, along with a potential role for some of them as outcome measures and index of treatment response. In this review, we provide an insight into the present knowledge on both existing and future biomarkers of iRBD and highlight the difference with PDRBD and PDnoRBD, including currently available treatment options.

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

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

0669 Disruptive Nocturnal Behaviors in PTSD Patients are Associated with More Severe Psychiatric Pathology

Abstract Introduction The similarities and differences between trauma associated sleep disorder (TASD) and REM sleep behavior disorder (RBD) are unclear. However, both REM sleep parasomnias are associated with disruptive nocturnal behaviors (DNB) that manifest as episodes of sleep-related vocalizations, and/or complex motor behaviors. Patients who have more DNB are more likely to have a higher prevalence of PTSD. Methods In a cross-sectional study, we examined the relationship between DNB severity and the severity of psychiatric symptoms in PTSD patients. 73 civilian patients with histories of complex developmental trauma (age 47.0 ±13.3 years; 89.6% female) met the DSM-5 criteria for moderate-to-severe PTSD. PTSD Checklist for DSM-5 (PCL-5) was used to obtain an index of current PTSD severity (37.41 ± 19.84; PCL-5 &amp;gt;30 cutoff for PTSD). DNB was defined as the sum of the two items 1f and 1g in the Pittsburgh Sleep Quality Index PTSD Addendum (PTSD-A). The participants rated how often during the past 1 month they had trouble sleeping because of the following: (PTSD-A Item1f) “Had episodes of terror or screaming during sleep without fully awakening” and (PTSD-A Item1g) “Had episodes of ‘acting out’ their dreams, such as kicking, punching, running or screaming”. We used a stepwise multiple regression analysis with DNB as the dependent variable and the variables described below as independent variables. Results We determined the following relationships: 1. PCL-5 (r=0.359, p=0.002); 2. Brief Symptom Inventory which includes Somatization (r=0.476,p&amp;lt; 0.001);Obsessive-compulsiveness (r=0.429, p&amp;lt; 0.001); Interpersonal Sensitivity (r=0.337, p=0.004); Depression (r=0.398, p&amp;lt; 0.001); Anxiety (r=0.449,p&amp;lt; 0.001); Hostility (r=0.577, p&amp;lt; 0.001); Phobic Anxiety (r=0.353, p=0.002); Paranoid Ideation (r=0.412, p&amp;lt; 0.001); and Psychoticism (r=0.414, p&amp;lt; 0.001); 3. Insomnia Severity Index (r=0.363, p=0.002); 4. Beck Suicide Scale or BSS (r=0.268, p=0.025); 5.Beck Anxiety Inventory (r=0.472, p&amp;lt; 0.001); and 6. Fear of Sleep(r=0.493,p&amp;lt; 0.001). Fear of Sleep Inventory (FOS) (Beta=0.442, t=4.258, p&amp;lt; 0.001) and Beck Scale for Suicidal Ideation (BSS) (Beta=0.300, t=2.887, p=0.005) emerged as the significant predictors of DNB. Conclusion DNB was correlated with a wide range of psychiatric pathology in PTSD. This suggests that DNB could be an integral feature of severe PTSD. To our knowledge, this has not been previously reported. Support (if any) None

0979 Obstructive Sleep Apnea in a Patient with Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS)

Abstract Introduction Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a rare disorder caused by an autosomal recessive biallelic pentanucleotide repeat expansion in the replication factor C subunit 1 (RFC1) gene. Clinical features include gait disturbances, impaired vibratory sensation, autonomic dysfunction, cough, and slow disease progression. Spinocerebellar ataxias are frequently associated with sleep disturbances, including REM sleep behavior disorders, insomnia, obstructive sleep apnea (OSA), and central sleep apnea. This is thought to be secondary to involvement of several nervous system structures including the cerebellum. OSA is caused by repeated obstruction of the pharyngeal airway leading to sleep disturbances and fatigue. It is likely that cerebellar insults such as CANVAS may play a role in upper airway obstruction and resultant OSA. However, there is little characterization of this relationship in the medical literature. Report of case(s) We report a case of a 52-year-old female with a past medical history of CANVAS, anxiety, and depression who was referred to sleep medicine for evaluation of worsening daytime fatigue and fragmented sleep. She reported daytime sleepiness, morning headaches, and gasping arousals. Her Epworth sleepiness scale score was markedly elevated at 19 (normal &amp;lt; 10), and she was subsequently referred for home polysomnography testing for sleep apnea. Home sleep testing revealed an apnea-hypopnea index of 12.5 events/hour and a minimum oxygen saturation of 85%. Conclusion This patient is at higher risk for sleep disruption due to her diagnosis of CANVAS. She presented with excessive daytime sleepiness and was found to have mild OSA on home sleep testing. Little is known about the presentation of OSA in patients with CANVAS. OSA treatment has the potential to improve sleep symptoms, quality of life, and mood disruption in this patient with an otherwise progressive and disabling neurologic disorder. Therefore early recognition and intervention of OSA are important in the care of patients with CANVAS. Given the disease’s progressive nature and lack of a cure, it is necessary to ameliorate quality of life however possible. OSA leads to persistent fatigue and may result in psychiatric disturbances, therefore, it is necessary to address sleep disturbances secondary to movement disorders to combat these outcomes. Support (if any)

The Accuracy and Reliability of Sleep Staging and Sleep Biomarkers in Patients with Isolated Rapid Eye Movement Sleep Behavior Disorder.

This study aimed to establish the diagnostic accuracy of a previously validated sleep staging system in patients with probable isolated REM sleep behavior disorder (iRBD), and to compare physicians' diagnoses of iRBD based on REM sleep without atonia (RSWA) to non-REM hypertonia (NRH), a sleep measure independently associated with Parkinsonian spectrum disorders. Twenty-six patients with a history of dream enactment behavior underwent a diagnostic PSG with simultaneous Sleep Profiler (SP) acquisition at two sites. PSG and SP records were sleep staged, and two sleep neurologists independently diagnosed iRBD based on the presence or absence of polysomnographic identified RSWA. Comparisons for PSG vs SP sleep staging and the qualitative presence or absence of PSG-based RSWA vs automated SP-detected NRH was performed using kappa coefficients (k), positive and negative percent agreements (PPA and NPA), and chi-square tests. The kappa scores from Sites-1 and -2 for PSG vs SP staging were different for Wake (k=0.82 vs 0.65), N2 (k=0.63 vs 0.72) and REM (k=0.83 vs.0.72). The by-site kappa values for stage N3 increased from 0.72 and 0.37 to 0.88 and 0.74 after PSG records were reedited. The kappa values for between-physician agreement in iRBD diagnoses were fair (k = 0.22). The agreement between each physician's iRBD diagnoses and NRH were also fair (k=0.29 and 0.22). Abnormal NRH agreed with at least one physician's iRBD diagnosis in 83% of the records. The PPA resulting from between-physician iRBD agreement was stronger and the NPA weaker than the values obtained from comparison of each physician's iRBD diagnosis and abnormal NRH. The potential utility of RSWA and stage N3 as neurodegenerative disorder biomarkers was influenced by between-site variability in visual scoring. The degree to which NRH was associated with iRBD was similar to the between-physician agreement in their diagnosis of iRBD using RSWA.

Continued Validation of the RBD Symptom Severity Scale (RBDSSS) in Participants of the North American Prodromal Synucleinopathy (NAPS) Consortium (P6-13.004)

Continued Validation of the RBD Symptom Severity Scale (RBDSSS) in Participants of the North American Prodromal Synucleinopathy (NAPS) Consortium (P6-13.004)

Evidence of Sympathetic Overactivity in Subjects with REM Behavior Disorder at Risk for Parkinson’s Disease (P6-13.002)

<h3>Objective:</h3> To evaluate sympathetic nervous system (SNS) activity in subjects with REM sleep behavior disorder (RBD) at risk of Parkinson’s disease, using imaging and autonomic functions markers. <h3>Background:</h3> While the nature of RBD is not completely understood, there is evidence that enhancement of noradrenergic activity may play a causative role, as suggested by evidence of persistent tonic discharge of locus coeruleus (LC) and RBD-triggering action of selective norepinephrine reuptake inhibitors. <h3>Design/Methods:</h3> Subjects &gt;50 years old with RBD with at least one pre-motor PD symptom (hyposmia, constipation, depression) were tested with a battery of autonomic evaluations including SCOPA-AUT questionnaire, cardiac MIBG scintigraphy, Heart Rate Variability (HRV) and neuromelanin sensitive MRI (NSMRI) of LC and substantia nigra (SN). Analyzed variables included: 1) for MIBG, late heart/mediastinum (H/M) ratio and washout ratio (WR); 2) for HRV, time and frequency domain measures; 3) for NSMRI, contrast-to-noise ratio (CNR) between LC and pons and between substantia nigra (SN) and cerebral peduncles. Results were compared with available normative ranges. <h3>Results:</h3> 14 subjects (11M, age 66.2±8.2) were enrolled. Average total SCOPA-AUT score was increased (12.1±6.7 vs 8.8±5.4), with gastrointestinal (2.4±2.1 vs 1.4±1.6), urinary (5.4±2.7 vs 3.9±2.4) and cardiovascular (0.86±1.10 vs 0.3±0.6) scores above normal ranges. MIBG late H/M ratio was reduced (1.45±0.31) with increased WR (33.0±14.8). HRV results showed enhanced sympathetic and low parasympathetic activity both in time (SDNN 106.8±73.2ms; RMSSD 21.9±10.9ms; PNN50% 6.7±8.4%) and frequency domain (LF/HF 3.4±1.8). NMSMRI showed high LC CNR (right 3.26±1.9 vs 2.08±0.5; left 2.95±0.9 vs 2.79±0.5). SN CNR was high (Medial 6.24±1.9 vs 4.57±0.8; Central 6.26±1.6 vs 3.43±0.6; Lateral 3.44±2.1 vs 3.05±0.5) and MDS-UPDRS motor scores were low (2.9±3.3). <h3>Conclusions:</h3> RBD subjects at risk for PD show abnormal autonomic scores, which appears to be driven by SNS overactivity, as suggested by increased MIBG WR, elevated LF/HF HRV ratios and increased LC and SN NSMRI signal. <b>Disclosure:</b> Dr. Tagliati has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbott. Dr. Tagliati has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Boston Scientific. Dr. Tagliati has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Supernus. Dr. Tagliati has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NeuroDerm. Dr. Tagliati has received publishing royalties from a publication relating to health care. Dr. Gregorio has nothing to disclose. Dr. Maghzi has nothing to disclose. Gloria Obialisi has nothing to disclose. Dr. Hogg has nothing to disclose. Dr. Malatt has nothing to disclose. Dr. Tan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Allergan. Dr. Artal has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Jazz Pharmaceuticals. Dr. Artal has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Private Parties. The institution of Dr. Artal has received research support from Jazz Pharma. The institution of Dr. Artal has received research support from Axsome. The institution of Dr. Artal has received research support from Suven. Dr. Shehata has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbott. Brian Renner has nothing to disclose. The institution of Dr. Sati has received research support from National Multiple Sclerosis Society. The institution of Dr. Sati has received research support from National Institutes of Health. Dr. Sati has received publishing royalties from a publication relating to health care.

Clinical Predictors of Survival in Probable Dementia with Lewy Bodies (P13-6.006)

Clinical Predictors of Survival in Probable Dementia with Lewy Bodies (P13-6.006)

Blepharoclonus as a Potential Novel Clinical Marker in Parkinson’s Disease (P3-11.009)

Blepharoclonus as a Potential Novel Clinical Marker in Parkinson’s Disease (P3-11.009)

Demographic and Clinical Profile of South Asian vs. non-South Asian Patients with Parkinson’s disease (P6-11.003)

<h3>Objective:</h3> To determine differences in demographic and clinical profile of South Asian vs. non-South Asian patients with Parkinson’s disease (PD) undergoing deep brain stimulation (DBS). <h3>Background:</h3> The majority of knowledge of PD has been gleaned from the discoveries made in familial and/or sporadic forms of PD in the Caucasian population. The transferability and the clinical utility of such biochemical and genetic discoveries to other ethnically diverse populations are unknown, with the South Asian population being underrepresented in PD research. <h3>Design/Methods:</h3> We performed a retrospective review of South Asian vs. non-South Asian PD patients undergoing STN-DBS between 2017–2022. Demographic data and clinical data were obtained. Pre-operative OFF/ON evaluation (dopamine challenge), neuropsychological testing scores (Dementia Rating Scale-2), motor and non-motor complaints were compared between the two groups using a Student’s T-test or chi-squared test as appropriate. <h3>Results:</h3> We compared data from 9 South Asian and 21 non-South Asian PD patients. Demographic characteristics were not different between the two groups. Alcohol use was less common in the South Asian population with a trend towards significance (88% never used vs. 57%, respectively, p = 0.09). At the pre-DBS evaluation, there was no difference in percent change in Unified Parkinson’s Disease Rating Scale (UPDRS) scores comparing OFF and ON evaluations, nor differences in DRS-2 scores. About 86% of non-South Asian patients complained of tremor pre-DBS, compared with only 44% in the South Asian group (p = 0.02). REM Behavior Disorder (RBD) was also less commonly reported in the South Asian vs. non-South Asian group (0% vs. 43%, respectively, p = 0.02). <h3>Conclusions:</h3> In this pilot study, we found differences in the clinical profile of South Asian vs. non-South Asian PD patients. Larger studies are needed to further examine these differences in the South Asian population which may lead to improved care and treatment in this group of patients. <b>Disclosure:</b> Mr. Srinivasan has nothing to disclose. Dr. Hargreaves has nothing to disclose. Ms. Caputo has nothing to disclose. Jasdeep Hundal has received research support from Rutgers University CAHBIR/BHI. Jasdeep Hundal has received research support from Horizon BCBS. Jasdeep Hundal has received research support from National Cancer Institute (NCI). Jasdeep Hundal has received research support from National Institute of Health/NIA. Dr. Danish has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for medtronic. Dr. Chen has nothing to disclose. Dr. Pal has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint. Dr. Pal has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Kyowa Kirin. Dr. Pal has stock in Baudax Bio. The institution of Dr. Pal has received research support from National Institutes of Health. The institution of Dr. Pal has received research support from Parkinson’s Foundation.

Composite Measures of Prodromal Parkinson’s Disease and the Probability of Phenoconversion at 3 Years (S37.003)

<h3>Objective:</h3> To assess the ability of composite measures of prodromal Parkinson’s disease (PD) to predict phenoconversion at 3 years. <h3>Background:</h3> Features suggestive of prodromal PD are individually insufficient for early disease detection. Using composite measures may improve predictive validity and capture a more representative patient population. <h3>Design/Methods:</h3> The study population comprised 19,757 individuals without PD at baseline (2014–2015). Two composite measures were created: i) the co-occurrence of probable REM sleep behavior disorder (pRBD), constipation and hyposmia, 3 major features of prodromal PD, and ii) a probability score which incorporated information on 8 risk (e.g., sex, physical inactivity) and 7 prodromal markers following the MDS research criteria. For each composite measure we calculated the positive predictive value (PPV) of being diagnosed with PD within 3 years. We additionally calculated the PPV for pRBD, constipation and hyposmia independently, and that of all 3 features along with parkinsonism. We repeated analyses restricting to participants &lt;70 years old. <h3>Results:</h3> Between 2014–15 and 2017–18, we identified a total of 86 incident PD cases. The PPV of being diagnosed with PD within 3 years was 2.48% for those with the 3 prodromal features, 2.62% for those with possible prodromal PD (score≥0.5) and 4.55% for those with probable prodromal PD (score≥0.8). The PPV of individual features was lower than those of the composite measures. Parkinsonism plus the co-occurrence of 3 features resulted in the highest PPV (11.8%). Measures based on the presence of 3 features performed somewhat better among men than women. The PPVs of measures based on the MDS score or parkinsonism were higher among those aged &lt;70 years. <h3>Conclusions:</h3> The ability to predict phenoconversion at 3 years was comparable between the two composite measures evaluated. The performance of composite measures was superior to that of individual features. Longer follow-up may be needed to better understand the validity of these measures. <b>Disclosure:</b> Mr. Torres has nothing to disclose. Dr. Hughes has received personal compensation for serving as an employee of Optum. The institution of Dr. Bjornevik has received research support from Michael J. Fox Foundation. The institution of Dr. Bjornevik has received research support from National Multiple Sclerosis Society. The institution of Dr. Bjornevik has received research support from Department of Defense. Dr. Cortese has received personal compensation in the range of $500-$4,999 for serving as a speaker at educational event with Roche. The institution of Dr. Hung has received research support from Parkinson’s Foundation. The institution of Dr. Hung has received research support from Rho, Inc.. The institution of Dr. Schwarzschild has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bial Biotech (indirectly, as a service of the Parkinson Study Group service). The institution of Dr. Schwarzschild has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen (indirectly, as a service of the Parkinson Study Group service). The institution of Dr. Schwarzschild has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB (indirectly, as a service of the Parkinson Study Group service). Dr. Schwarzschild has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. The institution of Dr. Schwarzschild has received research support from NIH. The institution of Dr. Schwarzschild has received research support from Parkinson’s Foundation. The institution of Dr. Schwarzschild has received research support from Michael J Fox Foundation. The institution of Dr. Schwarzschild has received research support from Farmer Family Foundation. Dr. Schwarzschild has a non-compensated relationship as a Chair, Executive Committee with the Parkinson Study Group that is relevant to AAN interests or activities. The institution of Dr. Ascherio has received research support from NIH and US Department of Defense .