bluuebunny/crossref_metadata_2025 huggingface dataset:
0724 Altered Brain Network Organization in Patients With Obstructive Sleep Apnea
Authors: Park H , Cha J , Kim H , Joo E
Published: May 2020

Introduction

Previous functional MRI (fMRI) studies have reported altered brain networks in patients with obstructive sleep apnea (OSA), but the extent of such abnormal connectivity was inconsistent across studies. Moreover, despite the important role of the cerebellum in respiration and OSA, connections of the cerebellum to the cerebral cortex have been rarely assessed. Here, we investigated functional network changes in cerebral and cerebellar cortices of OSA patients.

Methods

Resting-state fMRI, polysomnography and neuropsychological (NP) tests data were acquired from 74 treatment naïve OSA patients (age: 45.8±10.7 years, apnea-hypopnea index: 46.4±18.5 /h) and 33 normal controls (39.6±9.3 years). Connectivity matrices were extracted by computing correlation coefficients from various ROIs, and Fisher r-to-z transformations. ROIs consisted of 234 regions matched to 17 functional networks, including 200 parcels of the cortex, and 34 parcels of the cerebellum. Between-group connectivity with age as a covariate was analyzed, and threshold for FDR correction was set at q<0.05. In the functional connections that showed the significant group differences, linear regression was conducted to examine the association between connectivity and composite score of NP tests in OSA patients.

Results

OSA subjects showed decreased attention, executive function, verbal fluency and verbal memory compared to controls. Resting-state functional connectivity was increased between regions involved in the default mode network (DMN), including left medial prefrontal, ventrolateral prefrontal and lateral temporal cortices. In OSA, the connectivity changes between these DMN areas negatively correlated with attention/executive function and verbal fluency. Multiple cerebellar regions showed reduces in connectivity with cerebral cortical areas including frontal eye field, temporoparietal junction, temporo-occipital gyrus, and parieto-occipital association cortex.

Conclusion

OSA affects mainly the DMN and cerebello-cerebral pathway. The disruption of function in these two networks are known to relate to sleep deprivation and respiratory abnormality. The abnormal DMN found in OSA patients further related to their cognitive impairment.

Support

This research was supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning, Republic of Korea (2017R1A2B4003120) and by Samsung Biomedical Research Institute grant (OTC1190671)
0730 Individuals Receiving Methadone For Medication-Assisted Treatment Of Opioid Use Disorder Show Evidence Of Respiratory Depression
Authors: Finlay M , Wilson M , Erwin J A , Hansen D A , Layton M E , Quock R M , Van Dongen H
Published: May 2020

Introduction

A well-established consequence of opiate use is respiratory depression during sleep, with a high prevalence of central sleep apneas. Medication-assisted treatment (MAT) is a widely used therapy for opioid use disorder (OUD) designed to reduce withdrawal symptoms and drug cravings. We investigated the presence of respiratory depression during sleep in patients receiving methadone-based opioid replacement treatment as part of a MAT program for OUD.

Methods

N=6 individuals (5 females, ages 43.8±12.8y, BMI 27.2±4.1kg/m2), who were within 90 days of methadone initiation, underwent in-laboratory overnight polysomnography (8h TIB, 22:00-06:00). Apneaic and hypopneic events were determined using AASM criteria.

Results

The average Apnea-Hypopnea Index (AHI) was 16.5±9.0 events/h, with 2 individuals exceeding the threshold of moderate sleep apnea (>15 events/h). 89.5% of the observed apnea-hypopnea events occurred during NREM sleep. Of all events, 57.1±16.3% were central apneas; and of all obstructive, central, and mixed apnea events, 93.0±14.3% were central apneas.

Conclusion

Individuals with OUD receiving methadone-based MAT may be at risk of respiratory depression during sleep, as evidenced by the frequent occurrence of central sleep apneas. Such risk could be a contributing factor in opioid overdose deaths. Currently, performing respiratory assessments during sleep is not considered standard of care in MAT programs. Our preliminary data suggest that monitoring and treatment of respiratory depression during sleep may be indicated in OUD patients on methadone-based MAT.

Support

Supported in part by a seed grant from the Washington State University Office of Research Advancement and Partnerships.
0732 Quantitative Characterization Of Sleep Disordered Breathing Dynamics
Authors: Chen S , Eden U , Prerau M
Published: May 2020

Introduction

Sleep-disordered breathing (SDB) is a dynamic process in which the rate of respiratory events is highly influenced by numerous covariates, such as sleep stage, body position dominance, time of night, and overall instability of sleep architecture. Additionally, respiratory event rate likely has history dependence, such that the likelihood of a respiratory event is influenced by the timing of previous events. Despite its dynamic nature, clinical diagnosis collapses the complex process of SDB to a single number measuring the average rate of respiratory event occurrence— the apnea-hypopnea index (AHI). Thus, potentially valuable information is being lost by ignoring SDB temporal dynamics and history dependence.

Methods

We apply a general point process framework to sleep apnea events to develop parametric models of a time-varying instantaneous apnea rate given clinical covariates (e.g. EEG power, sleep stage, body position). Develop models of apnea history dependence, describing the likelihood of events given past event times. In doing so, we are able to compute an “instantaneous AHI”, which measures the moment-by-moment event rate, which evolves temporally as a function of other clinical observations as well as event history. We apply our model to data from the MESA cohort (include number of subjects, male/female here). We then applied dimensionality-reduction methods to assess any population phenotypes.

Results

For every subject, we computed a time-varying AHI for each time point in their polysomnogram and estimated the influence of each of the measured covariates on the instantaneous rate. Results showed that the greatest predictor of apnea events were related to history dependence. Clustering analysis showed no distinct clusters, but rather a constant gradient of changes in history dependence.

Conclusion

These results suggest that the greatest predictor of an apnea event onset is the timing previous event. Moreover, the way in which previous events influence subsequent events can be used as a means of phenotyping, paving the way towards identifying optimal personalized treatment.

Support

National Institute of Neurological Disorders and Stroke Grant R01 NS-096177
0740 Quality of Life in Phase 3, Placebo-Controlled, Double-Blind, Randomized Withdrawal Study of JZP-258 in Adults with Narcolepsy with Cataplexy
Authors: Foldvary-Schaefer N , Thorpy M J , Dauvilliers Y , Roy A , Tang L , Skowronski R , Šonka K , Bogan R K
Published: May 2020

Introduction

Narcolepsy negatively impacts health-related quality of life (HRQoL). Sodium oxybate is a standard of care for the treatment of cataplexy and excessive daytime sleepiness in narcolepsy. JZP-258 is an oxybate product candidate with 92% less sodium. Efficacy and safety of JZP-258 were established in a double-blind randomized withdrawal study in adults with narcolepsy with cataplexy.

Methods

Participants 18-70 years of age began JZP-258 treatment during a 12-week, open-label, optimized treatment and titration period, followed by a 2-week stable-dose period (SDP). Participants were then randomized to receive placebo or continue JZP-258 treatment during a 2-week, double-blind, randomized withdrawal period (DBRWP). HRQoL assessments included the 36-Item Short Form Health Survey Version 2 (SF-36) and 5-level EuroQoL 5-Dimensions Self-Report Questionnaire (EQ-5D-5L).

Results

201 participants enrolled; 134 were randomized and received at least 1 dose of double-blind study medication (efficacy population; placebo, n=65; JZP-258, n=69). Decreased scores (worsening) were observed in participants randomized to placebo compared with participants randomized to continue JZP-258 treatment for the SF-36 physical component summary (median [Q1, Q3], −1.92 [−3.46, 1.73] for placebo and −0.03 [−2.07, 2.41] for JZP-258; nominal P=0.02), SF-36 mental component summary (−1.92 [−6.28, 1.34] for placebo and 1.55 [−1.88, 3.78] for JZP-258; nominal P=0.03), and EQ-5D-5L visual analog scale (−5.00 [−10.0, 5.00] for placebo and 0 [0, 5.00] for JZP-258; nominal P=0.01). No change was observed in the EQ-5D-5L crosswalk index (0 [−0.05, 0.03] for placebo and 0 [−0.01, 0.03] for JZP-258; nominal P=0.39). The overall safety profile of JZP-258 was similar to sodium oxybate.

Conclusion

HRQoL worsened in those randomized to placebo during DBRWP but remained stable in participants who continued JZP-258 treatment.

Support

Jazz Pharmaceuticals
0743 The Pharmacokinetic Adverse Event Relationship for FT218, a Once-Nightly Sodium Oxybate Formulation
Authors: Seiden D , Grassot J , Monteith D , Dubow J
Published: May 2020

Introduction

Sodium oxybate is an effective treatment for excessive daytime sleepiness and cataplexy in patients with narcolepsy. The approved formulation requires twice-nightly dosing: at bedtime and 2.5 - 4 hours later, which results in two distinct Cmax’s. FT218 is a controlled-release formulation of sodium oxybate intended for once-nightly dosing, using Avadel’s proprietary Micropump™ technology. The objective of this study was to evaluate the pharmacokinetic-adverse event (AE) relationship for FT218, an investigational once-nightly sodium oxybate formulation.

Methods

Six single-dose, randomized, crossover studies that assessed the pharmacokinetics of FT218 at 4.5, 6, 7.5 and 9 g in healthy voluntters were used in this analysis. Lattice plots, “spaghetti” plots, and scatter plots of individual gamma hydroxybutyrate concentrations and indicators when AEs by system, organ, or class (SOC) were created to determine any PK-AE relationship.

Results

A total of 129 healthy volunteers received single doses of FT218 between 4.5 - 9 g. Most AEs, specifically for the neurological and gastrointestinal SOC, occurred close to Tmax, during the Cmax period, which for FT218 was around 1.5-2 hours after dosing. These AEs were known AEs associated with sodium oxbyate. There appeared to be no clear correlation between individual plasma GHB concentrations levels and AEs between subjects. Individual AEs were equally distributed above and below the mean population Cmax and AUCinf for the dataset.

Conclusion

In general, adverse events for FT218 occurred around Tmax. There was no clear population toxicokinetic range for when AEs occur with FT218, but mostly individual thresholds. Since it appears AEs are related to Cmax, and FT218 only has one Cmax compared to two with the currently available product, it is hypothesized that FT218 will have a favorable safety profile compared to twice-nightly dosing.

Support

This work was supported by Avadel Pharmaceuticals
0750 Nocturnal Sleep Stability and Cerebrospinal Fluid Orexin-A Levels: Sleep and Wake Bouts
Authors: Barateau L , Lopez R , Chenini S , Rassu A , Scholz S , Lotierzo M , Cristol J , Jaussent I , Dauvilliers Y
Published: May 2020

Introduction

The orexin (ORX)/hypocretin system stabilizes sleep-wake regulation by sustaining long periods of wakefulness in humans and animals. We aimed to evaluate the relationships between cerebrospinal fluid (CSF) ORX levels and markers of nocturnal sleep stability assessed by polysomnography (PSG) in humans.

Methods

Nocturnal PSG data and CSF ORX levels of 300 drug-free subjects (55% men, 29.9±15.5 years old, mean ORX levels 155.1±153.7 pg/mL) with a complaint of hypersomnolence were collected in the National Reference Center for Narcolepsy, France. Several markers of nocturnal sleep stability were analyzed: wake (WB), sleep bouts (SB), and sleep/wake transitions. Groups were categorized according to ORX levels: two categories (≤110, >110 pg/mL, the current established threshold of ORX-deficiency), and tertiles (≤26,]26;254], >254 pg/mL); and were compared using logistic regression models. Results were adjusted for age, gender and body mass index.

Results

ORX-deficient subjects had more WB, SB, and sleep-wake transitions than the others. The WB duration was longer and the SB duration shorter in ORX-deficient category. The proportion of the shortest WB (30 sec) was lower in the ORX-deficient category whereas the proportion of WB above 1 min 30 sec was higher. The proportion of SB ≤ 14min was higher among ORX-deficient patients, with opposite results for longer SB. Subsequent analyses performed in the population categorized according to tertiles of CSF ORX-A confirmed all these findings, with a strong dose-response effect of ORX levels in post-hoc comparisons. All results remained highly significant in adjusted statistical models.

Conclusion

This study provides a strong evidence of the direct effect of ORX on nocturnal sleep stabilization in humans. WB and SB are reliable markers of nighttime sleep stability, strongly correlated to CSF ORX-A levels in a dose dependent way. These PSG biomarkers are promising to be applied in clinical and research settings.

Support

none
0762 Efficacy Of Pitolisant In Patients With High Burden Of Narcolepsy Symptoms
Authors: Davis C W , Kallweit U , Krahn L E , Vaughn B , Thorpy M J
Published: May 2020

Introduction

Recent literature suggests that histamine may play an important role in narcolepsy. This post hoc analysis evaluates the efficacy of pitolisant, a histamine 3 (H3)-receptor antagonist/inverse agonist, in patients with high burden of the main narcolepsy symptoms.

Methods

Data were pooled from 2 randomized, placebo-controlled, 7- and 8-week studies of pitolisant (individually titrated; maximum dose, 35.6 mg/day) in adults with narcolepsy. Analyses included 3 independent patient subgroups: baseline score of >16 on the Epworth Sleepiness Scale (ESS), sleep latency of ≤8 minutes on the Maintenance of Wakefulness Test (MWT), and ≥15 cataplexy attacks per week.

Results

The analysis populations included 108 patients for the ESS (pitolisant, n=54; placebo, n=54), 105 for the MWT (pitolisant, n=59; placebo, n=46), and 31 for cataplexy (pitolisant, n=20; placebo, n=11). Mean change in ESS from baseline was significantly greater for pitolisant (-6.1) compared with placebo (-2.6; P=0.0002). A significantly greater percentage of pitolisant-treated patients were classified as treatment responders: for ESS score reduction ≥3, 68.5% in the pitolisant group versus 35.2% in the placebo group (P=0.0006); for final ESS score ≤10, 35.2% versus 9.3%, respectively (P=0.0026). Mean increase in sleep latency on the MWT was significantly greater for pitolisant (7.0 minutes) compared with placebo (3.4 minutes; P=0.0089). Decrease in mean weekly rate of cataplexy was significantly greater for pitolisant (baseline, 21.8; final, 3.9) compared with placebo (baseline, 20.9; final, 18.2); the rate ratio was 0.35 (95% CI, 0.26‒0.47; P<0.001). The adverse event profile in the analysis populations was consistent with the known safety profile for pitolisant; headache was the most common adverse event in pitolisant-treated patients (10.0%-20.4%).

Conclusion

In patients with severe symptom burden, pitolisant produced significantly greater improvements in excessive daytime sleepiness and cataplexy compared with placebo, highlighting the important role of histamine in narcolepsy.

Support

Bioprojet Pharma and Harmony Biosciences, LLC.
0776 Differences in Well-Being in Dayworkers Compared to Shift Workers: A Study of United States Navy Sailors
Authors: Shattuck N L , Matsangas P
Published: May 2020

Introduction

On United States Navy (USN) ships, most sailors are shift workers, required to support 24/7 operations. However, ~15% of the ship’s company are solely dayworkers who do not work in shifts. It is often assumed that the quality of life for dayworkers is better than that of shift workers. This study compared the well-being of dayworkers with that of shift workers.

Methods

Longitudinal, naturalistic observations were made of sailors (N=926; 18-59 years of age, ~80% males, ~84% enlisted personnel) on seven US Navy ships while performing their normal underway duties. Sleep-related attributes (actigraphy, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Insomnia Severity Index), mood (Profile of Mood States), and work/rest patterns were assessed.

Results

Dayworkers (DW; n=98) were on average older (p=0.001) and more senior (p=0.001) than shift workers (SW). Of the dayworkers, 31% reported elevated daytime sleepiness (SW:45.5%; p=0.008), 64.2% were poor sleepers (SW:82.6%; p<0.001), and 26.3% had ISI score≥15 (SW:24.8%; p=0.782). Also, 13.8% of the dayworkers had ESS>10 and ISI≥15 (SW:16.8%; p=0.626).Dayworkers had better mood (Total Mood Disturbance, anger/hostility, vigor, fatigue; all p<0.050), slept more (7.03±0.74hrs sleep/day; SW:6.52±1.03hrs; p<0.001) and had more consolidated sleep (1.1±0.3 sleep episodes/day; SW:1.4±0.6; p<0.001). Yet, split sleep was commonplace for both groups (DW:~62%; SW:~92%).The two groups do not differ (all p>0.300) in their use of caffeinated beverages (82%-86%), use of nicotine products (30%-36%), or having a regular exercise routine (69%-75%). In both groups, ~9% of sailors drank caffeinated beverages, used nicotine products and did not have an exercise routine (p=0.999). Dayworkers worked 10.1 hours/day, i.e., 1.7 hours/day less than watchstanders (p<0.001).

Conclusion

Quality of life of dayworkers is a bit better when compared to shift workers, but sleep-related issues are evident in almost all US Navy sailors. Living and working on a naval vessel takes a toll on almost everyone aboard. A culture change is required!

Support

Supported by the Naval Medical Research Center’s Advanced Medical Development Program, the US Navy 21st Century Sailor Office, and the US Navy OPNAV N1.
0779 Circadian Entrainment in 12h Night Shift Workers: The Environmental Lights Matter?
Authors: Choi S , Park H , Joo E
Published: May 2020

Introduction

Shift workers frequently suffer sleep disturbance in relation with the atypical work schedules. In particular, night shift workers are exposed to inevitable sunlight or bright indoor lights during the morning hours that may disturb their daytime sleep. We aimed to find out the optimal environmental lights to facilitate circadian entrainment of 12h-shift workers by assessing melatonin profiles in the morning and daytime sleep quality.

Methods

We enrolled 12h-shift female nurses working at one hospital (n=10, mean age 29.4±3.5 years). The schedules of participants are identical such as day-day-night-night shifts and four consecutive off days. Participants admitted to the laboratory at 9:00 following 2nd night shift schedule. Saliva melatonin was taken six times every 30 minute from 10:00 to 12:30 under two different lighting conditions with organic light emitting diodes (OLED) or light emitting diodes (LED) with 150 lux of light intensity. Dim light condition (10 lux) was conducted as controls. Three sessions were randomly ordered with 8-10 days intervals. Participants were allowed to sleep after 12:30 with light off and woke up ad libitum.

Results

Melatonin concentration had decreased gradually from 10.6±11.4 to 5.0±8.2 pg/ml. Among three different lighting conditions, there were no statistical differences in salivary melatonin and sleep parameters recorded by polysomnography. Circadian entrainment in night shift workers was defined as that salivary melatonin concentration had maintained above 5 pg/ml at the time to bed. 20% of sessions (6/30) were classified as circadian entrainment (CE) and 80% (24/30) were as non-entrainment (NE). Mean melatonin concentration was 22.1±11.2 in CE and 3.9±4.1 pg/ml in NE (p<.001). CE showed significantly shorter sleep latency (0.5±0.3 vs. 1.5±1.4 min, p=.025) and wakefulness after sleep onset (13.6±6.3 vs. 27.9±16.8%, p=.015), and higher sleep efficiency (94.6±2.6 vs. 88.7±6.3%, p=.011) than NE. The number of each lighting condition was not different between CE and NE (p=.847).

Conclusion

This is a preliminary study with small number of participants. We found that environmental lights including dim light did not affect daytime sleep of 12h shift workers. Instead, daytime sleep quality was influenced by circadian entrainment with higher melatonin concentration in the morning.

Support
0780 Effect Of A Sleep/Circadian Friendly Protocol On The Outcomes Of Patients Admitted To The Medical Intensive Care Unit: A Randomized Control Trial
Authors: Wakefield C , Morrow J , Hamati F , Sanzo G , Peterson S , Balk R A , Burgess H , Swanson G , Keshavarzian A
Published: May 2020

Introduction

Critically ill patients often suffer from fragmented sleep due to light and noise in the intensive care unit (ICU). We investigated whether placing patients in a sleep/circadian friendly protocol improved patient-reported sleep quality and ICU outcomes.

Methods

Patients were included if they were expected to have a >24-hour stay. Exclusion criteria included age <18 years, pregnancy, frequent overnight assessments, poor prognosis, pre-existing cognitive impairment, and severe psychological disorders. Patients were randomized to a sleep/circadian protocol or control protocol. Demographic, treatment, sound (dB), light (lux), patient-reported sleep, and medical outcomes were collected. Those who were not maintained in the sleep/circadian protocol were combined with the controls for statistical analysis. Univariate analysis was performed with Chi-Square test and Wilcoxon rank-sum test.

Results

Sixty-one patients were enrolled: 28 randomized to sleep/circadian protocol, 33 to control protocol. 14 subjects were excluded from analysis due to developing criteria for exclusion. Nine patients (median age 50 years, 6 females) maintained in the sleep/circadian protocol, 13 patients were not maintained in sleep/circadian protocol and 25 patients in control protocol (median age 64 years, 20 females). There was no difference in age, gender, or race between groups (p> 0.05). Median ICU first overnight dB level (10:00pm-6:00am) was 44.2 (±2.7) for sleep/circadian protocol and 50.5 (±4.9) for combined group (p= 0.008). Median ICU first overnight lux (10:00pm-4:00am) was 2.28 (±61.3) in sleep/circadian protocol and 18.42 (±90.9) in combined group (p=0.0374). A continued stay in the sleep/circadian protocol resulted in decreased total decibel level (p= 0.0018) decreased total overnight lux exposure (p= 0.0025) and decreased reported awakenings in first night (p= 0.0175). There were no differences in ICU length of stay, inpatient mortality, or readmission rates between groups (p>0.05). Three patients developed delirium, all originally randomized to control group.

Conclusion

We report on the successful outcomes associated with a sleep/circadian friendly protocol within a large tertiary center medical ICU which resulted in significant decreases in objectively assessed noise and light, and subjectively reported nocturnal awakenings. We continue to collect data to determine if the sleep/circadian friendly protocol should be permanently implemented in the ICU.

Support

None.
0796 Dipyridamole for the Treatment of RLS: Preliminary Results of a Cross-Over, Placebo-Controlled, Double-Blind Trial
Authors: Garcia-Borreguero D , Granizo J , Ferre S
Published: May 2020

Introduction

Recent animal models of restless legs syndrome (RLS) suggest that brain iron deficiency is associated with a hypoadenosinergic state, with downregulation of adenosine A1 receptors (A1R) in the striatum. Dipyridamole is a non-selective inhibitor of ENT1/ENT2 (the main reuptake mechanism of adenosine) and increases thereby extracellular adenosine. We hypothesized that treatment with dipyridamole would improve RLS symptoms more than placebo.

Methods

We performed a randomized, double-blind, placebo-controlled clinical trial on 15 previously untreated idiopathic RLS patients that underwent a two week treatment with either 300 mg dipyridamol or placebo (randomized for the order of treatments), following a cross-over design. Treatment started with a dose of 100 mg/day, followed by a forced up-titration to 200 mg on day 4, and to 300 mg on day 7. Severity was assessed at baseline, day 7 and day 14 of each treatment condition by means of the IRLS and CGI scales. The primary endpoint was therapeutic response (50% improvement in IRLS total score).

Results

Fifteen patients (nine women), never before treated with dopaminergic agents, completed both arms of the study. Mean age was 60,2 (±7,1), and the mean duration of illness was 6,03 (±3,1) yrs. IRLS score improved during treatment with dipyridamole from a mean (±S.D.) of 24,36 (±3,3) to 9,78 (±3,4), in contrast to a change from 23,9 (±3,8) to 16,6 (±3,7) under placebo (p< 0.05). Corresponding improvements on the CGI were 61,3% and 11,8% for dipyridamole and placebo, respectively. 7/ 15 patients improved by more than 50% during treatment with dipyridamole vs. 4/15 under placebo. Main side effects were abdominal cramps, diarrhea, dizziness, and flushing.

Conclusion

These preliminary results suggest that dipyridamole is an effective agent on RLS symptoms. It also provides evidence of hypoadenosinergic mechanisms playing a central role in RLS.

Support

No funding was provided for this investigation.
0811 Periodic Limb Movements In Patients With Dysautonomia
Authors: Tallavajhula S
Published: May 2020

Introduction

Periodic Limb Movements in Sleep (PLM) have been thought to result in increase in sympathetic tone in sleep, tachycardia, elevated systolic blood pressure and therefore elevation in risk of cardiovascular disease. However, evidence of a direct causative relationship has been elusive. We discuss the presence of PLM in patients with dysautonomia, proposing that autonomic dysfunction may be either a causative factor for PLM or share common pathogenesis with PLM.

Methods

Three patients with dysautonomia, referred to the TIRR Memorial Hermann Hospital neurological sleep disorders center with varying sleep-related symptoms were studied with polysomnography, recorded under AASM guidelines. PLM were scored using standard criteria described in the AASM scoring manual.

Results

The three patients described all carried a diagnosis of dysautonomia, diagnosed by tilt table testing. The first patient was an 18 year old woman with complaints of palpitations during sleep and frequent arousals. Her PLM index was 49.8. Serum ferritin level was pending. The second patient was a 35-year-old woman who complained of nonrestorative sleep. Polysomnogram demonstrated a PLM index of 17.6. Ferritin level was 36 ng/mL. The third patient was a 34-year-old woman with insomnia who was also found to have a PLM index of 15.1. Her serum ferritin level was 24. She underwent therapeutic iron infusions and experienced substantial improvement in subjective sleep quality. None of the patient described symptoms of restless legs syndrome or had any bleeding disorders to explain low ferritin levels.

Conclusion

The patients described above all were relatively healthy young women with symptoms of dysautonomia and disturbed sleep. It would be unusual for young individuals to present with PLM which are commonly associated with advancing age. In at least one patient, iron infusions improved sleep quality dramatically. Work needs to be done to establish relationship between autonomic imbalance and PLM, suggesting that the previously thought unidirectional relationship, [i.e. PLM causing change in sympathetic tone] may actually be bidirectional.

Support

None
0817 Abnormal REM Sleep Atonia Control In Patients With Chronic Post-traumatic Stress Disorder
Authors: Feemster J , Steele T , Tao Y , Rivera S , Gossard T , Teigen L , Timm P , McCarter S , St. Louis E
Published: May 2020

Introduction

Post-traumatic stress disorder (PTSD) is characterized by persistent mental and emotional stress following one or more significant physical or psychological traumatic incidents earlier in life. Vivid recall of the events, including traumatic nightmares, and prominent sleep disturbance are usual in PTSD. Previous studies have suggested that PTSD may share some clinical features with idiopathic REM sleep behavior disorder (iRBD) including altered REM sleep without atonia (RSWA) levels. Our group has previously found evidence for altered RSWA control in patients with psychiatric disease, including a pilot sample of PTSD patients with iRBD. We aimed to comparatively analyze RSWA levels between patients with PTSD, PTSD and RBD (PTSD+RBD), iRBD, and controls.

Methods

We selected 18 PTSD, 18 PTSD+RBD, 15 iRBD, and 51 healthy control patients matched for age and sex from the Mayo Clinic Center for Sleep Medicine’s polysomnography database for RSWA quantification. RSWA amounts in the submentalis (SM) and anterior tibialis (AT) were quantitatively analyzed as a percentage of REM sleep duration, in accordance with previously published methods. Non-parametric analyses were performed to compare RSWA, patient demographics, and PSG data across groups. Significance was set at p < 0.016.

Results

Patients with PTSD had significantly higher RSWA than controls in all RSWA density measures (p < 0.016 for all). All measures of RSWA, excluding average SM duration, were significantly greater in PTSD+RBD patients compared with controls (p < 0.016 for all). Within the PTSD group, patients on antidepressants did not have significantly higher RSWA in any of the measures. PTSD+RBD patients had significantly higher SM Phasic, AT Any, SM+AT Any, and Tonic RSWA measures than PTSD patients (p < 0.016 for all).

Conclusion

PTSD patients have significantly higher RSWA than controls, with PTSD+RBD patients having higher RSWA levels than PTSD patients. These data provide the first evidence for abnormal RSWA control in patients with chronic PTSD. This provides evidence of a unique biology in PTSD that could imply a future risk for neurodegenerative disease in PTSD similar to RBD patients. Further prospective studying will need to be performed on patients with PTSD to understand the unique biology.

Support
0824 Improving Subjective Sleep Quality Measures Through Mindfulness Training in the Elderly: Preliminary Data from the Mindfulness Sleep Therapy (MIST) Study
Authors: Perini F , Foong Wong K , Teng J , Hassirim Z , Lin J , Leow Z , Lee Henderson S , Fan Q , Lo J C , Ong J C , Doshi K , Lim J
Published: May 2020

Introduction

Poor sleep is a modifiable risk factor for multiple chronic disorders. Mindfulness-based therapies potentially improve sleep by enhancing awareness and acceptance of internal and external experiences, thus reducing pre-sleep hyper-arousal. In this pre-registered, randomized controlled trial, we tested the effect of mindfulness-based treatment for insomnia (MBTI) on subjective sleep quality measures (Pittsburgh Sleep Quality Questionnaire, PSQI) in the elderly.

Methods

Participants above 50 years old with sleep difficulties (PSQI ≥ 5) (mean (sd) age = 62.0 (6.35), 44 female) attended either an 8-week MBTI (N = 34) or sleep hygiene education and exercise program (SHEEP; N = 35). Before and after the interventions, we collected PSQI, insomnia symptoms and features measures (Pre-Sleep Arousal Scale, PSAS; Insomnia Severity Index, ISI; Dysfunctional Beliefs and Attitudes about Sleep, DBAS-30), mindfulness (Five-Facets Mindfulness Questionnaire, FFMQ), and mood and anxiety (Back Depression Inventory, BDI; State-Trait Anxiety Inventory, STAI). PSQI and PSAS (N = 26 to date) were collected at 6-month follow-up. Data were analysed with repeated-measures ANCOVA with group as a between-subject variable for the first 69 participants who completed the study.

Results

We observed significant improvement across both groups for sleep measures (PSQI: F1,67=36.442, p<.01; PSAS-Cognitive: F1,67=12.664, p<.01; ISI: F1,67=36.442, p<.0; DBAS: F1,67=28.749, p<.01) and mood (BDI: F1,67=26.393, p<.01; STAI-State: F1,67=4.608, p=.04; STAI-Trait: F1,67=7.687, p<.01), but not for Mindfulness (F1,67=2.256, p=.14) nor PSAS-somatic. No significant group by time interactions were found. We observed a correlation between PSQI decreases and FFMQ increases in MBTI (r=-.53, p<.01), but not in SHEEP (r=-.07, p=.70) participants. ANCOVA of 6-month PSQI data revealed a significant group by time interaction (F1,24=19.525, p=.03), with reduction from baseline in MBTI (t12=4.769, p<.01), but not in SHEEP group (t12=3.813, p=.08).

Conclusion

Preliminary results support MBTI as an accessible but effective behavioural intervention with potential long-term benefits for improving sleep and mood, and reducing cognitive-emotional arousal in the elderly.

Support

This study was supported by an award from the 7th grant call of the Singapore Millennium Foundation Research Grant Programme
0830 Hormonal Contraceptive Use and Sleep: A Systematic Review and Meta-Analysis
Authors: Bezerra A G , Pires G , Andersen M L , Tufik S , Hachul H
Published: May 2020

Introduction

The effects of hormonal contraceptives on sleep has been matter of debate in current literature. While some articles observed a sleep promoting effect and reduced sleep disordered breathing, others have failed to detect any result or even detected a worse sleep pattern in women using hormonal contraception. As the literature has been growing on this field, a systematic review is necessary to gather and compare all the studies in a comprehensive way.

Methods

A bibliographic search was conducted in Pubmed, Scopus and Web of Science. Studies were selected first based on titles and abstracts, followed by full text analysis and data extraction. Only original studies evaluating women using hormonal contraception were considered eligible. Both objective and subjective sleep-related outcomes were extracted for analyzes. Individual effect size for each articles was calculated using regular or standardized mean differences and meta-analyses were conducted using a DerSimonian and Laird random effects model.

Results

After the bibliographic search, 1787 non-duplicated articles were included in our initial data screening. Articles sample was reduced to 114 records after abstract screening and to ten studies after full text analyses. The following sleep outcomes were eligible for meta-analysis: Pittsburgh Sleep Quality Index (PSQI - 3 studies), total time in bed (4), subjective total sleep time (4), objective total sleep time (3), sleep latency (6), sleep efficiency (6). None of them resulted in statistically significant effects of contraceptive use and the effect size ± 95% interval of confidence overlapped the zero value.

Conclusion

Hormonal contraceptives is not associated to any alteration in sleep patterns in women. This conclusion should be restricted to a general framework, since our sample does not allowed stratified analyses. Future studies should consider the effect of specific hormonal composition (ex.: combined vs. progestogen-only contraceptives) and administration route (contraceptive pills vs. levonorgestrel intrauterine device).

Support

AFIP, CAPES, CNPq
0835 Elucidating the Effect of Sleep Apnea on Cognitive Health: A Preliminary Report
Authors: Ramos A R , Alperin N , Junco B , Lee S , Hernandez-Cardenache R
Published: May 2020

Introduction

We aim to determine the cognitive domains associated with obstructive sleep apnea (OSA) age-related brain atrophy in a sample of middle-aged to older males.

Methods

We evaluated consecutive treatment naïve male OSA patients (AHI≥15) without dementia, stroke or heart disease (infarction, heart failure), from March to November of 2019. We obtained demographic variables, vascular risk factors, the Epworth sleepiness scale (ESS) and the Pittsburgh sleep quality index (PSQI). We also obtained computerized neurocognitive testing with the Go-NoGo Response Inhibition Test, Stroop Interference Test, Catch Game Test, Staged Information Processing Speed Test, Verbal Memory Test and Non-Verbal Memory Test. We derived domain-specific Z-scores age and education adjusted for global cognition, memory, attention, processing speed and executive function. Pearson correlation was used to evaluate bivariate associations between the sleep exposures and neurocognitive outcomes. Linear regression was used to evaluate associations between AHI and neurocognitive domains, adjusting for the ESS.

Results

A total of 15 participants 40 to 76 years of age, 73% of Hispanic/Latino background, completed neurocognitive testing. The average ESS was 8.2±6.0, PSQI=5.7±4.9, and AHI=48.9±25.5. Hypertension was seen in 66% and diabetes in 27%. The AHI was correlated with global cognition (r= -0.66; p=0.008), memory (r= -0.73; p=0.002) and attention (r= -0.67; p =0.007), but not executive function or processing speed. In addition, the AHI correlated with verbal memory (r= -0.76; p=0.001), but not with non-verbal memory. In adjusted models, the AHI was associated with global cognition (β= -0.60; p=0.05) and decreased memory (β= -0.85; p=0.006). However, the association with attention was explained by the ESS. The PSQI was not correlate with the cognitive domains.

Conclusion

In this pilot-study, the AHI was associated with decreased global cognition, and verbal memory accounting for sleepiness. Findings suggest the left-hippocampus as a region vulnerable to early age-related brain loss in OSA.

Support

Scientific Advisory Committee, Pilot grant, Miller School of Medicine; R21AG056952; R21HL140437.
0845 The Difference in Sleep Characteristics of Chronic Insomnia Disorder According to Gender and Age
Authors: Hong J , Lee H , Yoon I
Published: May 2020

Introduction

Impacts of age and gender on sleep have been reported in normal population, but rarely in chronic insomnia disorder (CID). This study aimed to investigate difference in sleep characteristics of CID according to gender and age.

Methods

The participants with drug-naïve CID and aged between 40 and 79 years were recruited. We compared subjective and objective sleep parameters between the middle-aged (40-64 years, N=86) and the elderly (65-79 years, N=50), and between men (N=45) and women (N=91). The subjective sleep quality and habitual sleep time were measured by Pittsburgh Sleep Quality Index (PSQI). The participants were asked to wear an actigraph for 4 days to obtain objective sleep parameters.

Results

In the PSQI, the elderly reported earlier bedtime and wake-up time (p=0.018; p=0.026), reduced total sleep time (TST) and sleep efficiency (p=0.003; p=0.011), and low sleep quality (p=0.034) compared to the middle-aged. However, according to the actigraphy, differences were observed only in the bedtime (p=0.016) and the wake-up time (p=0.002) between the two age groups. Between genders, the actigraphy showed that the male patients woke up earlier than the female group (p=0.015); except for this finding, there was no significant gender effect. Meanwhile, regarding gender and age interactions, the elderly women with CID showed longer time in bed (TIB) with increase in both TST and wake after sleep onset (WASO) compared to the middle-aged women. The elderly men showed decreased TIB and TST, and slightly decreased WASO than the middle-aged men.

Conclusion

The elderly with CID show more subjective sleep complaints than the middle-aged CID despite little difference in objective sleep characteristics, which suggests that the elderly CID may seek medical help more than the middle aged. As women with CID get older, they increase time spent in bed to maintain sleep time, but with resultant increase in wake.

Support

None
0849 Association Of Sleep Disturbance With Neck Circumference, Body Mass Index & Blood Pressure In Pregnant Japanese Women
Authors: Morioka A , Asaka y
Published: May 2020

Introduction

Snoring is one of the symptoms of sleep-disordered breathing. Sleep-disordered breathing is associated with blood pressure in pregnant women. However, studies reporting this association have been conducted overseas, and there is a lack of research in the Japanese context, where women have different lifestyles and physical attributes. The aim of this study is to clarify the association of sleep disturbance with physical factors in pregnant Japanese women.

Methods

A cross-sectional study was conducted with 80 pregnant Japanese women. The assessments for statistical analysis included the Japanese versions of the Pittsburgh Sleep Quality Index (J-PSQI) and Epworth Sleepiness Scale (JESS), as well as snoring frequency, blood pressure, and body mass index (BMI) before and during pregnancy.

Results

Participants’ average gestational age was 26.23±7.56 weeks, and the J-PSQI and JESS scores were 5.5±2.6 and 9.7±4.2, respectively. The average neck circumference was 33.4±2.6cm, and BMI before and during pregnancy was 21.0±2.9cm and 23.1±3.1cm, respectively. Among the participants, 42.5% displayed habitual snoring. These women had significantly higher BMI and weight before and during pregnancy than those who did not snore habitually. Participants with lower diastolic blood pressure and pre-pregnancy weight had significantly higher JESS scores. Participants with thick necks (neck circumference≥33.4cm) had significantly higher BMI and weight before and during pregnancy, as well as lower J-PSQI scores, than those with thin necks.

Conclusion

In pregnant Japanese women, neck circumference and BMI before and during pregnancy were lower than among pregnant women from other countries. However, Japanese women displayed a greater tendency toward snoring during pregnancy compared to women from other countries. Snoring was associated with obesity before and during pregnancy. However, the results suggest that thinness of physique prior to pregnancy is a risk factor for sleep disturbance during pregnancy.

Support
0857 Factors Associated With Sleep Health Among Middle-aged And Older Adults
Authors: Lorenz R A , Auerbach S L , Li C , Chang Y
Published: May 2020

Introduction

The concept of Sleep Health (SH) was developed to provide a multidimensional framework consisting of characteristics of sleep that have been closely associated with physical and mental well-being. Identification of key factors associated with SH can identify targets for intervention for its improvement. This study aimed to identify factors related to SH among middle-aged and older adults.

Methods

A valid Sleep Health Composite Measure was recently developed from the data of the 2014 Core Survey of the Health and Retirement Survey and was used to assess overall SH in middle-aged and older adults. Spearman’s correlations, T-test, and Kruskal-Wallis tests were used to explore the association of SH with age, gender, self-rated health, chronic disease burden, disability, pain, and modifiable lifestyle behaviors (physical activity, smoking, alcohol, sleep medication).

Results

Our sample included 6,095 adults with mean age of 68 years (SD=10.1; range 50-99 years). The majority were female (59.7%) and white (77%). Correlations showed significant moderate associations between SH and self-rated health (r=.404), sleep medications (r=.390), pain (r=-.315). There were significant but small associations between vigorous activity (r=-.193), alcohol (r=.112), currently smoking (r=-.089) and SH. SH was significantly worse among women compared to men (t(6093)=6.996, p<0.001). Furthermore, SH scores were significantly different between middle-aged versus older adults (p<0.001); varying levels of self-rated health (p<0.001), number of chronic diseases (p<0.001), and degree of physical disability (p<0.001).

Conclusion

These findings provide evidence of factors related to SH among middle-aged and older adults, providing targets for intervention to improve health in this population. Age-related differences in relation to SH indicate intervention tailored for middle-aged adults may improve health outcomes as they age. Future studies are warranted to extend these findings using multivariable statistical approaches.

Support

This study was supported by the University at Buffalo Clinical and Translational Science Institute (CTSI) funded by the National Institutes of Health (Lorenz PI).
0876 Obstructive Sleep Apnea, Low PAP Use, and Daytime Sleepiness are Associated with Weight Regain Following Bariatric Surgery in Adolescents with Severe Obesity
Authors: Kaar J L , Patten L , Kaizer A , Hawkins S M , Moore J M , Alioa M S , Inge T H , Simon S L
Published: May 2020

Introduction

Significant weight loss is seen following bariatric surgery, leading to an ameliorative effect on obesity-related comorbidities such as OSA. Weight loss maintenance is a priority, and identifying factors that may be associated with weight loss outcomes following bariatric surgery is of high importance. The current study examined whether OSA symptoms and PAP therapy were associated with weight outcomes following bariatric surgery in adolescents.

Methods

Participants from the Teen-LABS Study, which follows adolescents undergoing bariatric surgery were examined. Demographic and anthropometric data, OSA diagnosis, and PAP prescription and self-reported usage information were assessed 6 months before surgery. Pediatric Sleep Questionnaire (PSQ) responses were utilized from baseline to 48 months post-surgery. All analyses were adjusted for time, age, sex, surgery type, and ethnicity.

Results

242 adolescents (76% female, 72% White, age at surgery = 16.6 [1.6] years) were included. 57% had a diagnosis of OSA at pre-surgical baseline, and 56% of adolescents with OSA reported PAP use at pre-surgery. BMI increase over time from year 1-4 post-surgery was 11% more for those with high PSQ severity compared to those with low PSQ severity (p = 0.01). Those with pre-surgical OSA that reported using PAP “often” or “always” at baseline had an 8% lower increase in BMI from year 1-4 post-surgery compared to those that reported using PAP “rarely” or “sometimes” at baseline (p = 0.004). Finally, endorsing daytime sleepiness on the PSQ was associated with a 11% greater increase in BMI during years 1-4 post-surgery (p = 0.01).

Conclusion

OSA and daytime sleepiness may be associated with greater weight regain following bariatric surgery in adolescents. Adherence to PAP therapy pre-surgery may be a protective factor in preventing or reducing weight regain following surgery. Daytime sleepiness may be an effect of OSA, or due to the insufficient sleep that is prevalent among adolescents. Research is needed to examine the impact of additional aspects of sleep health such as duration, timing, and quality on health outcomes, as well as the impact of PAP adherence and sleep interventions on weight regain following bariatric surgery in adolescents with severe obesity.

Support

None.