bluuebunny/crossref_metadata_2025_split huggingface dataset:
0624 Samelisant (SUVN-G3031), Baseline Characteristics from a Phase-2 Study Evaluating Efficacy and Safety in Patients with Narcolepsy
Authors: Nirogi Ramakrishna , Ravula Jyothsna , Jayarajan Pradeep , Goyal Vinod Kumar , Jetta Satish , Shinde Anil , Benade Vijay , Jasti Venkat 
Published: May 2022

Abstract

Introduction
Histamine H3 receptor (H3R) antagonists/inverse agonists increase histaminergic neurotransmission and offer a therapeutic option for the treatment of narcolepsy. Samelisant (SUVN-G3031) is a potent H3R inverse agonist and exhibits very high selectivity over other targets. In orexin knockout mice, samelisant produced wake-promoting and anticataplectic effects suggesting its potential therapeutic utility in the treatment of excessive daytime sleepiness and cataplexy associated with narcolepsy. It showed dose-dependent H3R occupancy at efficacy doses. Safety and tolerability studies in animals and healthy human volunteers suggested a favorable risk/benefit profile for samelisant.Samelisant is being evaluated in a Phase-2, multicenter, double-blind, placebo controlled, parallel-group study in patients with narcolepsy with or without cataplexy (ClinicalTrials.gov Identifier: NCT04072380).

Methods
Eligibility criteria for the study include subjects diagnosed with narcolepsy as per ICSD-3, aged between 18 to 50 years with an Epworth Sleepiness Scale (ESS) score of ≥12 and mean maintenance of Wakefulness Test (MWT) time of &lt;12 min. A total of 171 subjects will be randomized into 3 treatment arms (placebo, samelisant 2 mg and samelisant 4 mg) in a fixed 1:1:1. Further, the randomization will be stratified according to the type of narcolepsy (Type-1 or Type-2). Each subject will receive either placebo or study drug once daily for 2 weeks. The primary efficacy endpoint is change in MWT score from baseline to week 2. Secondary endpoints are change in ESS and Clinical Global Impressions of Severity (CGI-S) from baseline to week 2. Safety will be monitored throughout the study by medical monitor and by an independent data safety monitoring committee. Baseline clinical and demographic data for the currently enrolled study is summarized descriptively. Since the study is blinded, a breakdown of baseline characteristics by treatment group will not be available until after completion.

Results
At the data cutoff date of Nov30, 2021, a total of 108 subjects were randomized in the study. The median age of subjects was 30 years (range: 18-50 years) with mean BMI of 26.4 (range: 18.3- 43.1 kg/m2). Overall, 58% subjects were of narcolepsy type-1, 69% were female and 74% were Caucasian. Mean (SD) baseline values of MWT and ESS were 6.20 (4.53) and 17.17 (2.93), respectively.

Conclusion
Baseline characteristics are consistent with the general narcolepsy population. The study is currently enrolling subjects with narcolepsy and the data readout is expected in Q3 2022.

Support (If Any)
None
0625 Characterization of Obstructive Sleep Apnea in Active-Duty US Military Personnel Receiving Interdisciplinary Care at the National Intrepid Center of Excellence
Authors: Hedglen Erin , Willing Maegan Paxton , Riley Mark , Srikanchana Rujirutana , Moxley Jasmine , Gottshall Jackie , Brooks Peter , Lippa Sara , Kenney Kimbra , Pickett Treven , DeGraba Thomas , Rhodes Chandler Sours , Werner J 
Published: May 2022

Abstract

Introduction
Among active-duty service members (ADSMs), obstructive sleep apnea (OSA) is associated with decreased quality of life and military readiness/retention. Limited evidence suggests mild traumatic brain injury (mTBI) patients have increased OSA incidence, but little is known about the underlying physiology. This study aims to characterize OSA in treatment-seeking ADSMs with a history of remote mTBI and/or persistent neurobehavioral symptoms to improve detection and early intervention.

Methods
This is a retrospective analysis of data collected from ADSMs attending the National Intrepid Center of Excellence Intensive Outpatient Program for persistent symptoms associated with mTBI. Sleep assessment included overnight polysomnography and self-report assessments of sleep quality, somatic and mood symptoms. OSA severity was determined by apnea-hypopnea index (negative: &lt;5, mild: 5-15, moderate/severe: ≥15). Group differences were assessed using analysis of covariance and pairwise least squares regression, controlling for age and body mass index, and corrected for multiple comparisons.

Results
Analyses included 574 ADSMs, mostly male (99%), with a mean age of 39.7. The majority (n=288; 50.2%) were OSA negative (OSA-neg); a third had mild OSA (m-OSA) (n=216; 38%); and a tenth were diagnosed with moderate/severe OSA (mod/s-OSA) (n=70; 12%). Mod/s-OSA patients had increased arousal index (p&lt;0.01), hypoxia time (p&lt;0.001), reduced total sleep time (p&lt;0.01) and sleep efficiency (p&lt;0.001) compared to m-OSA and OSA-neg patients. M-OSA patients had an increased arousal index compared to OSA-neg patients (p&lt;0.01). Patient groups did not significantly differ on subjective measures of sleep (i.e., quality, sleepiness), post-concussive, or behavioral health symptoms (anxiety, depression, post-traumatic stress symptoms, alcohol misuse).

Conclusion
In our sample of treatment-seeking ADSMs, nearly half presented with OSA according to cut-scores derived for AHI, greater than that expected in the general population. As reported in civilian populations, mod/s-OSA patients demonstrated worse objective sleep measures compared to m-OSA and OSA-neg patients, yet in our sample their self-reported symptom severity did not differ. These findings suggest a low threshold for OSA screening is needed in the symptomatic mTBI population and that multiple factors other than OSA likely contribute to perceived sleep disturbances and neurobehavioral symptoms.

Support (If Any)
None.
0628 Epilepsy Control and Night Sleep Duration and Afternoon Siesta
Authors: Al-Abri Mohammed , Al-Asmi Abdullah 
Published: May 2022

Abstract

Introduction
The relationship between sleep and epilepsy has long been recognized but understanding the association between seizure control and sleep duration is not well explored. The study aims to describe the sleep habits in people with epilepsy (PwE) and explore the association between sleep habits, particularly afternoon napping and level of seizure control and anti-epileptic drugs (AEDs).

Methods
this is a cross-sectional study of adult epilepsy patients attending neurology clinic. Sleep parameters are measured using actigraphy for one week and home sleep apnea testing to rule out obstructive sleep apnea (OSA).

Results
total of 250 PwE were screened and 129 patients (male & female) completed the study with mean age of 29.75 ± 9.18 years and mean body mass index (BMI) of 27.12 kg/m2. There was significant association between night sleep duration and time of wake up and number of AEDs (adjusted R2=0.026, P=0.03 & P=0.04 respectively). There is also significant association between number of seizures per night and afternoon napping (adjusted R2=0.043, P=0.05). Other sleep parameters did not reveal any significant association with level of epilepsy control neither with number of AEDs (P&gt;0.05).

Conclusion
The study described that PwE with uncontrolled epilepsy on multiple AEDs are practicing sleep habits that involved longer afternoon napping and shorter sleep duration.

Support (If Any)
Sultan Qaboos University
0631 Actigraphy-based and self-reported sleep quality and cognitive function in midlife
Authors: Leng Yue , Knutson Kristen , Carnethon Mercedes , Yaffe Kristine 
Published: May 2022

Abstract

Introduction
Growing evidence suggests that sleep disturbance might be a risk factor for cognitive impairment in older adults. However, the association between device-based sleep duration, quality and cognitive function in midlife is poorly understood.

Methods
We examined 526 Black and White men and women who completed the sleep examination at baseline from 2003 to 2005 and had cognition evaluated 11 years later from the Coronary Artery Risk Development in Young Adults (CARDIA) study, Sleep duration and quality was assessed objectively using a wrist activity monitor and subjectively by Pittsburgh Sleep Quality Index (PSQI). We evaluated cognitive function using the Digit Symbol Substitution Test (DSST), Stroop test, Rey Auditory Verbal Learning Test (RAVLT), Montreal Cognitive Assessment (MoCA) and Letter Fluency and Category Fluency tests.

Results
This study included 305 (58%) women and 229 (44%) Black people, with a mean age of 40.1±3.6 years at baseline. After adjustment for age, sex, race, education, smoking, body mass index, depression, physical activity, hypertension and diabetes, actigraphy-measured sleep fragmentation index (calculated as the sum of the percentage of time spent moving and the percentage of immobile periods ≤ 1 minute) was significantly associated with all measures of cognition, except for fluency. Every standard deviation increase in sleep fragmentation index was associated with worse executive function [DSST (b=-1.80, 95%CI: -3.20, -0.41) and Stroop (b=-1.23, -0.25, -2.21)], worse verbal learning [RAVLT (b=-0.41, 95%CI: -0.66, -0.82)] and worse global cognition [MOCA (b=-0.41, 95%CI: -0.74, -0.16)]. Poorer sleep maintenance was associated with worse verbal learning (RAVLT) and global cognition (MOCA) of a similar magnitude. We did not find any association between objective sleep duration or subjective sleep quality and cognition.

Conclusion
Poorer actigraphy-measured sleep quality rather than sleep duration was associated with worse executive function, verbal learning and global cognition among middle-aged Black and White men and women. Sleep quality is important for cognitive health in midlife.

Support (If Any)
0633 The relationship between sleep and Parkinson's disease progression: A Mendelian Randomization study
Authors: Matar Elie , Mahjoub Mahiar 
Published: May 2022

Abstract

Introduction
Sleep disturbances and disorders are common in Parkinson’s disease and significantly impact quality of life. Often, such sleep disturbances are considered sequelae of neurodegeneration affecting sleep-wake circuitry. However, there is emerging evidence that sleep disturbance may itself play a causal role in neurodegenerative processes via altered clearance of pathological proteins. Whether sleep disturbance affects the pathological progression of Parkinson’s disease is unknown. Recently, a several genetic variants have been discovered for sleep-related parameters through genome-wide association studies (GWAS) providing a unique opportunity to examine the evidence for causal relationships through the use of the Mendelian randomization.

Methods
To elucidate the causality between sleep disorders and progression of Parkinson’s disease, we performed two sample Mendelian randomization analysis using genetic variants identified from publicly available GWAS data for sleep variables including insomnia, sleep duration, chronotype, napping and daytime sleepiness as exposure variables. Outcome measures were derived from a large collective GWAS of PD progression (N=4093 cases) including the Unified Parkinson’s disease rating scale (UPDRS total and UPDRS- III), motor fluctuations, Age of onset of PD (PD-AOO), Mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MOCA). The robustness of results was examined using conventional Mendelian randomization sensitivity analyses.

Results
Genetic liability to increased sleep duration was associated with a lower rate of progression of motor symptoms in PD using UPDRS-III score. Meanwhile insomnia was associated with increased rate of motor progression of PD. Predisposition to daytime sleep was associated with lower rates of progression of cognitive decline in PD measured using MMSE. No robust relationships were determined between markers of progression and chronotype or daytime napping. Statistical measures showed significant pleiotropy for the relationships identified.

Conclusion
Sleep-related variables may have a deterministic role in the clinical progression in Parkinson’s disease and may represent a modifiable target for altering the trajectory of neurodegeneration.

Support (If Any)
0635 Validation of a clinical scale for defining RBD severity in participants of the North American Prodromal Synucleinopathy (NAPS) consortium
Authors: Lee-Iannotti Joyce , Choudhury Parichita , Busicescu Andrea , Rangan Pooja , Shprecher David , Fantini Maria-Livia , Ju Yo-El , Boeve Bradley , Postuma Ronald 
Published: May 2022

Abstract

Introduction
The objective of this study is to assess the validity of the REM Sleep Behavior Disorder (RBD) symptom severity scale (RBDSSS) and its correlation to the clinical global impression of severity (CGI-S) in a cohort of participants enrolled in the North American Prodromal Synucleinopathy (NAPS) study. RBD is a prodromal marker of α-synucleinopathies with no standardized tool for assessing severity in clinical or research practice. Development of a reliable scale is essential to understand risk of phenoconversion and to monitor response to treatments, particularly in future neuroprotective clinical trials.

Methods
Participants and their bedpartners enrolled in the NAPS cohort filled out an 8-item questionnaire, developed by the International RBD Study Group, assessing frequency and severity of dreams, vocalizations, movements, and injuries associated with RBD, with higher scores indicating more severe symptoms. The CGI-S is a 7-point scale ranging from normal (1) to most severely ill (7) and was completed by a clinician based on an independent interview with the participant ± their bedpartners. Data was included when patient (RBDSSS-PT) and bedpartner (RBDSSS-BP) responses were both available. Total scores were derived by multiplying assigned point values for frequency and severity (for each question) and summing them for individual RBDSSS-PT scores (total possible=54) and RBDSSS-BP scores (total possible=38).

Results
This cohort (n=212) included in this analysis was predominantly male (n=175) with a mean ± SE age of 65.16 ± 1.46 years. The median (interquartile range) for RBDSSS-PT, RBDSSS-BP and CGI-S was 11 (4-17), 8 (4-14.3) and 3 (3-4), respectively. Non-parametric Spearman’s rank correlation coefficients (rs) for each variable pair are as follows: RBDSSS-PT vs. RBDSSS-BP, rs=0.575; RBDSSS-PT vs. CGI-S, rs=0.641; RBDSSS-BP vs. CGI-S, rs=0.463 (P&lt;0.0001).

Conclusion
A moderate correlation was observed between RBDSSS-PT and RBDSSS-BP suggesting good construct validity for the scale. CGI-S correlated moderately with RBDSSS-PT and weakly with RBDSSS-BP. Future, larger studies are needed to explore this as a possible universal and clinically applicable scale for designation of RBD disease burden and prognostication.

Support (If Any)
0642 Characterizing Actigraphy-Measured Sleep Disturbance in Veterans and Service Members with Post-traumatic Headache following Mild Traumatic Brain Injury
Authors: Li Yihan , Rau Holly , Engle Conner , Gunn Heather , Raskind Murray , Mayer Cynthia 
Published: May 2022

Abstract

Introduction
Post-traumatic headache (PTH) frequently occur following traumatic brain injury (TBI) is particularly prevalent in Veterans with deployment-related TBI. PTH is associated with a range of physical and mental health symptoms, including post-traumatic stress disorder (PTSD), depression, anxiety, post-concussive symptoms, and subjective sleep complaints. Subjective sleep disturbance is associated with greater pain severity, and headaches (HA) are associated with poorer sleep. Poor sleep may be a mechanism by which PTH exerts both direct and indirect effects on health outcomes Despite the high prevalence of sleep problems in individuals with PTH, we know little about sleep disturbance in Veterans and military personnel with PTH. This study sought to characterize the relationship between objective sleep disturbance and HA in Veterans and military personnel with chronic PTH following mild TBI.

Methods
Veterans and active-duty service members (N=39, Mage= 49.4, 89.7% male) were included from a larger study evaluating prazosin as prophylactic treatment for persistent PTH. Participants completed baseline measures of PTSD symptoms, insomnia, sleep quality, HA frequency and impairment, as well as 7-day actigraphy, sleep diary, and HA logs. Actigraphy-derived sleep parameters include sleep onset latency (SOL), total sleep time (TST), sleep efficiency (SE), and wake after sleep onset (WASO). Daily HA logs were used to assess HA severity and duration. Analyses were conducted in SPSS 26.0 using multilevel modeling, controlling for the effects of time.

Results
Preliminary results suggest number of HA days at baseline was significantly associated with self-reported sleep quality (r=-.398, p= .016), but not with subjective SOL, TST, or WASO. Number of HA days was significantly correlated with actigraphy-measured WASO (r=.178, p=.003). Actigraphy-measured SOL, SE, WASO, and TST were not significantly associated with same-day HA severity and duration.

Conclusion
This preliminary data suggest examination of sleep fragmentation may be important in enhancing our understanding of PTH and related impairment. Findings support the importance of using both subjective and objective measures in the assessment of sleep in Veterans and service members with PTH.

Support (If Any)
This project was supported by a VA Career Development Award 5IK2RX001136 from the United States Department of Veterans Affairs Rehabilitation Research and Development Service. The contents of this work do not represent the views of the Department of Veterans Affairs or the United States government.
0644 Longitudinal sleep instability contributes to cognitive decline and Alzheimer’s pathology: Findings from the Seattle Longitudinal Study
Authors: Keil Samantha , Schindler Abigail , Wang Marie , Lim Miranda , Piantino Juan , Elliott Jon , Werhane Maddi , Thomas Ronald , Iliff Jeffrey 
Published: May 2022

Abstract

Introduction
Although emerging data suggest a link between sleep duration, aging, and dementia diagnosis, the impact of longitudinal patterns of sleep behavior on Alzheimer’s disease-associated pathology and cognitive decline remains unclear.

Methods
Utilizing longitudinal data on self-reported sleep duration collected within the Seattle Longitudinal Study (n=535 subjects, age 75.18 +/- 11.6 years), we first used a Cox proportional hazard (CPH) regression model to evaluate the overall effect of mean sleep duration, longitudinal changes in sleep duration, and variability in sleep duration on the development of cognitive decline, including APOE4 genotype, sex, years of education, and depression as covariates within the model. In a secondary study, within the subset of subjects for whom postmortem histopathological assessment has been conducted (n=105 subjects, age 86.6 +/- 8.0 years), we used supervised machine learning to predict Alzheimer’s pathology, measured by CERAD neuritic plaque score and Braak stage.

Results
Multivariable CPH regression analysis demonstrated that there was a significant association between cognitive decline risk and APOE status (hazard ratio 2.28, 95% CI 1.41-3.69, p&lt;0.005), depression (hazard ratio 1.09, 95% CI 1.04-1.14, p&lt;0.005), sleep stability (hazard ratio 2.78, 95% CI 1.43-5.43, p&lt;0.005), and sleep restlessness (hazard ratio 0.70, 95% CI 0.51-0.97, p&lt;0.03). Notably, sleep variability across time and not median sleep duration was significantly associated with cognitive impairment. Adding these sleep parameters to the model improved model performance (base model concordance = 0.66, model including sleep = 0.72). Sleep parameters also improved performance on models predicting Alzheimer’s disease-associated pathology.

Conclusion
While these findings support a mixed effect of sleep duration on cognitive decline and the development of Alzheimer’s-associated neuropathology, they further suggest that variability in longitudinal sleep duration may exert a previously unappreciated influence on these pathological processes. Future studies should seek to replicate these findings in an independent cohort and to assess whether sleep variability of different time scales (weeks, years, decades) exerts similar effects on these outcomes.

Support (If Any)
0646 Sleep Disorders and Sleep Medication Use in Youth with Persistent Tic Disorders
Authors: Ricketts Emily , Qu Christine , Rissman Ariel , Swisher Valerie , Burgess Helen , Coles Meredith , Colwell Christopher , Piacentini John 
Published: May 2022

Abstract

Introduction
Sleep disturbance is present in 80% of youth with persistent tic disorders (PTD). However, studies examining rates of sleep disorders in youth with PTD are limited, and reports on sleep medication use in this population are lacking. Such knowledge would inform understanding of assessment and treatment needs of youth with PTD. Therefore, the present study examined rates of sleep disorders and sleep medication use among youth with PTD, and their associations with tic severity and ADHD symptoms.

Methods
Participants were 52 parents of youth with PTD who responded to an internet survey evaluating sleep-wake patterns. Youth were predominantly male (n = 37, 72.5%); and 88.5% (n = 46) were reported to have Tourette’s disorder and 11.5% (n = 6) were reported to have persistent motor tic disorder. Parents provided demographics and medical history, including lifetime sleep disorder diagnosis by a health professional and current prescription or over-the-counter sleep medication use. Parents rated youth tic severity (Parent Tic Questionnaire) and ADHD symptom severity (Swanson, Nolan, and Pelham-IV Parent Rating Scale).

Results
Descriptive statistics and independent samples t-tests were performed. Per parent report, 39.2% (n = 20) of youth with PTD had one or more lifetime sleep disorders. Insomnia (n = 9, 17.3%), nightmares (n = 9, 15.7%), sleep walking (n = 5, 10.0%), bruxism (n = 5, 10.0%), and restless leg syndrome (n = 5, 10.0%) were most commonly endorsed. Fifty percent of parents of youth with PTD endorsed youth sleep medication use. The most commonly endorsed sleep medications were melatonin (n = 23, 44.2%), valerian (n = 6, 11.5%), and diphenhydramine (n = 5, 9.6%). There were no significant group differences in tic severity or ADHD symptom severity.

Conclusion
Findings highlight the presence of disorders of sleep initiation and maintenance, parasomnias, and sleep-related movement disorders in youth with PTD. Results indicate that sleep medication use, particularly melatonin, is common in this population. Future research is needed to test the efficacy of melatonin use for addressing sleep problems in youth with PTDs.

Support (If Any)
NIMH K23 MH113884 funding to Dr. Ricketts.