bluuebunny/crossref_metadata_2025_split huggingface dataset:
0425 Severity of Insomnia Symptoms Differ by Cognitive Status in Adults with Down Syndrome
Authors: Desai S , Chen I Y , Doran E , Hom C , Nguyen D D , Benca R M , Lott I T , Mander B A 
Published: May 2020

Abstract

Introduction
Sleep is disturbed in Down syndrome (DS), with sleep apnea and insomnia prevalent throughout life. Sleep disturbance increases dementia risk and is more prevalent in dementia in non-DS populations. However, relationships between sleep and clinical status in DS remains unclear. We examined informant-reported sleep in adults with DS, with or without a consensus diagnosis of dementia, and related the severity of sleep disturbances to measures of adaptive behavior.

Methods
Insomnia (selected from Children’s Sleep Habits Questionnaire), daytime sleepiness (modified ESS), sleep apnea risk (modified STOP-BANG), and adaptive behavior (Vineland Adaptive Behavior Scales; VABS-3) questionnaires were collected from informants for 47 DS adults (52.1±6.6 years) enrolled in a Alzheimer’s disease biomarker study. Participants’ clinical statuses were categorized as cognitively unaffected (clinically significant impairment absent; n=38, 51.0±6.2 years), or as having definite dementia (clinically significant decline present; n=9, 56.6±6.4 years) using a standard consensus diagnosis procedure. Age was compared between groups using an independent samples t-test. ANCOVA was used to compare insomnia, daytime sleepiness, sleep apnea risk, and adaptive behavior measures across groups, while controlling for age. Partial correlation analyses examined associations between sleep measures and VABS-3 measures while controlling for clinical status.

Results
Participants categorized as definite dementia were older (t=-2.381, p=0.022). ANCOVA determined that insomnia symptoms, but not daytime sleepiness or apnea risk, were more severe in definite dementia participants (F=5.567, p=0.023), even when controlling for age. VABS-3 subscale scores differed by clinical status (all save play and leisure scores p&lt;0.017). Partial correlation analyses adjusting for clinical status indicated that insomnia symptom severity worsened with lower adaptive functioning (e.g., daily living skills—coping r=-0.41, p=0.007; socialization r=-0.33, p=0.024) regardless of clinical status.

Conclusion
These findings indicate that insomnia may be related to functional impairment and dementia in DS adults, and raises the possibility that insomnia treatments may influence dementia course and clinical symptomatology in DS.

Support
NIH U01AG051412
0427 Bicuculine Increased the Cataplexy in the Male Taiep Rats: An Animal Model of Narcolepsy with an Inherent Tubulopathy
Authors: Cortes C , Eguibar J R , Ibarra-Hernandez J M 
Published: May 2020

Abstract

Introduction
Narcolepsy is a hypersomnolence that is characterized by sleep fragmentation, sleep paralysis, hypnagogic hallucinations and cataplexy that is characterized by atonia induced by strong emotions. The amygdala is the trigger for cataplexy through GABAergic mechanisms. Taiep is a myelin mutant with TUBB4A tubulopathy which showed spontaneous episodes of atonia or induced by manipulations from the tail or the thorax. EEG recordings during immobility episodes (IE′s) had a cerebral cortex desynchronized associated to theta rhythm in the hippocampus. The aim of this sturdy was to analyze the effects of bicuculine administration on IE′s and sleep-wake pattern on adult male taiep rats.

Methods
We used 6 taiep male rats at 9 months of age. The subjects (Ss) lived in individual acrylic cages with water and food pellets available ad libitum, under a 12:12 light-dark cycle (lights on at 0700), with controlled temperature and humidity recording room. All Ss were implanted to record EEG, EMG and EOG to characterize EI′s. We evaluated a basal 24 h EEG recording and then after bicuculine i.p. administration of 0.5, 1 y 1.5 mg/Kg every 48h. We measured the number, mean duration and latency to the first IE′s.

Results
The duration of IE′s increased 527% with 1 mg/Kg and reach 700% with 1.5 mg/Kg of bicuculine (P&lt;0.01) with respect to saline-treated control group. Importantly, the frequency of IEs did not differ among the groups and did not affect the number of awake, slow wave or rapid eye movements sleep phases.

Conclusion
Bicuculine, a specific GABA antagonist, modify the duration of IES but not their frequency supporting a role of GABAergic mechanism on IE′s. It is relevant because sodium oxybate, an indirect GABA agonist, reduced cataplexy and improved sleep quality on narcoleptic patients.

Support
CONACYT grants 243333 and 243247 to CC and JRE, respectively and from VIEP-BUAP 2019 to CA in Neuroendocrinología BUAP-CA-288.
0448 Scaled-Up Sleep Apnea Endotyping Using Polysomnography for Clinical Use
Authors: Finnsson E , Jónsson S Æ , Ólafsdóttir G H , Loftsdóttir D L , Helgadóttir H , Ágústsson J S , Wellman D A , Sands S A 
Published: May 2020

Abstract

Introduction
Sleep apnea is caused by several key endophenotypic traits namely pharyngeal collapsibility, poor muscle compensation, ventilatory instability (high loop gain), and arousability from sleep (low arousal threshold). Already, measures of these traits have shown promise for predicting outcomes of therapies (oral appliances, surgery, hypoglossal nerve stimulation, CPAP, or pharmaceuticals) and thus may be an integral part of future precision sleep medicine with treatments administered based on underlying pathophysiology. However, currently, the novel methods developed for endotyping from polysomnography are computationally expensive and can only be performed by the original authors or their collaborators due to the need for technological expertise. Here we present a cloud-based method for endotyping sleep apnea from polysomnography for use in the clinical arena.

Methods
For cloud-based use, we optimized the Phenotype Using Polysomnography (‘PUP’) method of Sands et.al. (2015-2018) by performing the following: Code was translated from MATLAB to Python; efficient methods were developed to detect breaths, calculate normalized ventilation (moving time-average), and model ventilatory drive (intended ventilation). The new implementation (‘PUP.py’) was validated by comparing the measured traits against the original values.

Results
38 manually scored clinical polysomnographic studies were endophenotyped using the two implementations. Results of the new implementation (‘PUP.py’) were strongly correlated with the original (p&lt;10-6 for all): collapsibility and compensation (ventilation at eupneic drive ‘Vpassive’: r=0.98; ventilation at arousal threshold, r=0.97), loop gain (r=0.96), and arousal threshold (r=0.92).

Conclusion
We successfully implemented the original method by Sands et.al. to scale up sleep apnea endotyping and make it available to a broader audience.

Support
This work was supported by the Icelandic Centre for Research RANNÍS, the European Union’s Horizon 2020 SME Instrument (733461), and the American Heart Association (15SDG25890059).
0460 Insomnia In 400 Women: Polysomnography, Immune Parameters, Depression and Anxiety
Authors: Akerstedt T , Ghilotti F , Schwarz J , Theorell-Haglöw J , Lindberg E 
Published: May 2020

Abstract

Introduction
Insomnia disorder has a very weak link to polysomnography (PSG) and so does sleep problems in the general population. The reason for this is not clear. One possibility is that the perception of disturbed sleep may be related to immune activation or anxiety/depression, without impairment of objective sleep.

Methods
400 women participated, constituting a representative sample of the city of Uppsala with oversampling of snorers. Insomniacs (N=41) were compared with normal sleepers in terms of polysomnography (PSG), immune parameters, anxiety and depression

Results
The results (after adjustment for age and BMI) show that C-reactive protein (CRP) reached a higher level (4.4±.5) in insomniacs (vs 2.3±.2 for normal sleepers) (p=.003) and lower subjective health (p=.000), while anxiety (p=.000) and depression (p=.000) (Hospital Anxiety and Depression Scale (HAD)) showed higher levels. PSG sleep continuity variables lacked association with insomnia, as did all sleep stage variables except for REM%, with a lower level in the insomnia group (p=.021). Interleukin 6 and Tumor Necrosis Factor alpha were not related to insomnia. CRP levels did not correlate significantly with anxiety or depression, but with subjective health (r=-.21, p=.000). A logistic regression analysis (excluding the variable subjective health) with insomnia as outcome (0/1) yielded as predictors CRP (OR=1.14, Ci= 1.05; 1.24, p=.000), depression (OR=1.21, Ci=1.06;1.38, p=.000) and anxiety (OR=1.15, Ci=1.02;1.30, p=.021).

Conclusion
It was concluded that increased CRP levels may be part of the subjective experience of insomnia.

Support
No external funding
0486 Impact of Intrinsic Factors on Efficacy of Lemborexant: Subgroup Analyses of SUNRISE-2
Authors: Moline M , Inoue Y , Kubota N , Pinner K , Perdomo C , Yardley J 
Published: May 2020

Abstract

Introduction
Lemborexant (LEM), a dual orexin receptor antagonist, demonstrated significant benefits vs placebo on patient-reported sleep outcomes in adults age ≥18y in SUNRISE-2 (NCT02952820; E2006-G000-303). The impact of intrinsic factors (sex, race, and region) on LEM efficacy outcomes was assessed.

Methods
SUNRISE-2 was a randomized, double-blind, global phase 3 study in adults age ≥18y with insomnia disorder (Full Analysis Set, n=949). Subjects received placebo (n=318) or LEM (5mg [LEM5], n=316; 10mg [LEM10]; n=315) for 6 months. At 6 months, placebo subjects were rerandomized to LEM for another 6 months (not reported here); LEM subjects remained on their assigned dose. Sleep diary-based (subjective) sleep onset latency (sSOL) and wake after sleep onset (sWASO) were assessed for prespecified patient subgroups including: sex (male [n=302], female [n=647]), race (white [n=679], black [n=76], Asian [n=178]), and region (North America [n=302], Europe/New Zealand [n=483], Asia [n=164]). Analyses were not controlled for multiplicity.

Results
LEM5 and LEM10 provided numerically greater median reductions (improvement) from baseline in sSOL vs placebo at 6 months in across all subgroups examined. Also, LEM5 and LEM10 led to mean reductions (improvement) from baseline at 6 months in sWASO for all subgroups. While several subgroups had small numbers of subjects, changes from baseline in sSOL and sWASO were in the direction of improvement in the majority of subgroups. Pharmacokinetic analyses showed no important differences in exposure by these factors.

Conclusion
LEM treatment demonstrated efficacy in improving sSOL and sWASO across patient subgroups, supporting common dosing instructions for both sexes and all races.

Support
Eisai Inc.
0487 Effects of Suvorexant on Sleep Architecture in Patients with Alzheimer’s Disease and Insomnia
Authors: Svetnik V , Wang T , Ceesay P , Ceren O , Snyder E , Bliwise D , Budd K , Hutzelmann J , Stevens J , Lines C , Michelson D , Herring W 
Published: May 2020

Abstract

Introduction
Suvorexant, an orexin receptor antagonist that enables sleep to occur via competitive antagonism of wake-promoting orexins, improved total sleep time (TST) in a sleep laboratory polysomnography (PSG) study of patients with AD and insomnia. Here we report on the effects of suvorexant on sleep architecture in the study.

Methods
This was a randomized, double-blind, 4-week trial (ClinicalTrials.gov NCT02750306). Participants who met diagnostic criteria for both probable AD dementia (of mild to moderate severity) and insomnia were randomized to suvorexant 10mg (could be increased to 20mg based on clinical response) or matching placebo. Overnight sleep laboratory PSG was performed on 3 nights: screening, baseline, and Night-29 (last night of dosing). Suvorexant differences from placebo in changes-from-baseline at Night-29 for sleep architecture were analyzed as exploratory endpoints.

Results
A total of 274 participants were included in the analysis (suvorexant N=135, placebo N=139). At Night-29, suvorexant improved TST by 28 minutes versus placebo (p=0.001). There were no significant differences between suvorexant and placebo in the % of TST spent in REM (1.3%, 95% CI: -0.5, 3.0), N1 (0.6%, 95% CI: -1.2, 2.5), N2 (-1.0%, 95% CI: -3.2, 1.2), or N3 (-0.6%, 95% CI: -1.8, 0.6). There was no significant difference between suvorexant and placebo in latency to REM (-5.4 minutes, 95% CI: -23.4, 12.7).

Conclusion
Suvorexant improves TST without altering the underlying sleep architecture in AD patients with insomnia.

Support
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA
0489 Initial Results from the Hypertension with Unsatisfactory Sleep Health (HUSH) Clinical Trial for Primary Care Patients with Insomnia and Comorbid Hypertension (INS-HTN)
Authors: Buysse D J , Ritterband L M , Yabes J G , Rollman B L , Strollo P J , Smith K J , Patterson C M 
Published: May 2020

Abstract

Introduction
Insomnia is commonly comorbid with, and may contribute to, hypertension. Cognitive-behavioral treatments improve insomnia, but their effects on hypertension are uncertain, and they are often unavailable in primary care practices, where most INS-HTN patients are treated. We evaluated the efficacy of Brief Behavioral Treatment for Insomnia (BBTI) and Sleep Healthy Using the Internet (SHUTi) compared to enhanced usual care (EUC) on insomnia and home blood pressure (HBP) in primary care patients with INS-HTN.

Methods
Patients were recruited via electronic health records from 67 primary care practices and randomized 2:2:1 to BBTI delivered via telephone/videoconferencing; SHUTi, an automated, web-based CBT-I program; or EUC including a patient education video. Assessments included self-report questionnaires, home sleep apnea testing, and one week of sleep diary and HBP, measured at Baseline and 9 weeks/ 6 months post-treatment. The primary outcome was the Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance scale. Linear mixed models were fitted for continuous variables on the intent-to-treat sample (n=548), adjusting for age and sex. Chi-square tests were used for proportions.

Results
Patients were 61.8±11.3 years old, 67.2% female, and 55.9% were taking hypnotics. Insomnia Severity Index (ISI) was 15.4±4.4, Apnea-Hypopnea Index 9.8±11.4, and HBP 130±14/81±9. BBTI and SHUTi were significantly better than EUC (p≤.002) at 9 weeks and 6 months on PROMIS Sleep Disturbance and Sleep-Related Impairment scales, ISI, and diary sleep efficiency, but had inconsistent effects on PROMIS depression and anxiety scales (p=0.001-0.9). Greater proportions of BBTI and SHUTi vs. EUC-treated patients had 9-week and 6-month ISI scores &lt;8 (p=.01, p=.04) and ISI changes scores ≥7 (p=.002, p=.003). HBP did not significantly differ by intervention group.

Conclusion
BBTI and SHUTi improved insomnia, but did not reduce HBP in patients with INS-HTN. These interventions appear suitable for dissemination and implementation in primary care, but may have limited effects on comorbid symptoms and conditions.

Support
NHLBI UH2/UH3 HL125103
0490 Development and Preliminary Evaluation of a Brief Intervention for Post-Deployment Insomnia
Authors: Mellman T , Howell M 
Published: May 2020

Abstract

Introduction
Sleep disturbances are common among previously deployed Veterans. Cognitive behavioral therapy for insomnia (CBT-I) has shown promise for Veterans but there are limitations and CBT-I may not optimally target the nocturnal vigilance conditioned by threatening environments. We developed and preliminarily evaluated a brief educational/behavioral intervention that combined established behavioral sleep principles with cognitive exercises intended to reduce the impact of vigilant thoughts and behaviors on sleep.

Methods
Participants were 40 Veterans recruited from the community and local VAMC who had been deployed to combat zones or hazardous duty areas. The mean age was 40, and the majority were male, African American, and screened positively for PTSD. They were assigned to the study intervention or an educational control that utilized a pamphlet promoting healthy sleep habits. Assignment at a 2:1 ratio was intended to allow for refinement of the study intervention during the early phase of the trial. Initial assessment was followed by a week of sleep diary collection, then two intervention sessions a week apart, followed by a repeat assessment. Participants of the study intervention were assessed again 3-months later.

Results
Improvements in sleep efficiency, ratings for feeling rested in the morning, and reduced Insomnia Severity Index scores were seen in the post-treatment week but did not differ between groups. At 3-months, these improvements were sustained in the 14 retained participants of the study intervention, engagement in vigilance reducing exercises remained high, and ratings of how rested one felt in the morning were significantly improved over ratings from the post-treatment week.

Conclusion
Brief behavioral intervention for post-deployment insomnia can provide benefits and cognitive exercises to reduce the impact of vigilant thoughts and behaviors warrant further evaluation.

Support
Supported by W81XWH-14-1-0066 from the Congressionally Directed Peer-Reviewed Medical Research Program of the Department of Defense
0493 Use of Sleep Aid Medication is Associated with Memory Deficits: A Population-Based Study
Authors: Dokkedal-Silva V , Oliveira M M , Galduroz J F , Tufik S , Andersen M L 
Published: May 2020

Abstract

Introduction
Use of medications to treat sleep complaints is a common practice that may incur in cognitive deficits. Evidence, beyond the well-described effects of benzodiazepines on cognition, still needs expansion. This study assessed the use of sleep aid medications of different classes and associated factors on prospective and retrospective memory in a representative populational sample from São Paulo.

Methods
Volunteers in the EPISONO study underwent evaluation through questionnaires and a complete polysomnography exam. A subsample of 500 volunteers (Mean Age=42.9 years; 307 women) was included. Users (N=250) and non-users (N=250; randomly selected among the non-using volunteers) of sleep medication were evaluated regarding scores in 8 subscales and the overall score of the Prospective and Retrospective Memory Questionnaire (PRMQ). Afterwards, users of classes of medications were compared. Covariates, including scores in psychiatric evaluation scales and polysomnographic findings, were added in both segments to identify the factors with highest interference in the results obtained.

Results
Medication users consistently performed worse in prospective memory and short-term internal-cued retrospective memory even when covariates were added. Scores in Beck Anxiety and Depression Inventories, Insomnia Severity Index and variables related to wakefulness and sleep architecture were the covariates with the highest interference in the results. When comparing types of medication, few differences were seen, suggesting that for such analysis, a sample with higher power would be appropriate.

Conclusion
Users of sleep medication presented impairment in prospective memory. Factors such as sleep architecture and continuity, as well as insomnia, anxiety and depression symptoms must be considered when evaluating cognitive deficits and pharmacological treatment in patients with sleep complaints, as they may participate in this relationship. Future studies are necessary to characterize the impact of different medication classes on prospective and retrospective memory.

Support
Our studies are supported by Associação Fundo de Incentivo à Pesquisa (AFIP) and Conselho Nacional de Desenvolvimento Científico Tecnológico (CNPq - Grant #133397/2017-3); S.T. and M.L.A. received CNPq fellowships.
0499 Predictors of Session Attendance in a RCT for CBT-I for Perinatal Insomnia
Authors: Rangel E , Asarnow L , Simpson N , Manber R 
Published: May 2020

Abstract

Introduction
Cognitive behavioral therapy for insomnia (CBT-I) is recommended as the first-line treatment for chronic insomnia disorder. However, early treatment dropout can negatively impact the success of treatment. In order to design effective strategies to reduce attrition we need to understand predictors of dropout. In this work, we focus on predictors of treatment session attendance among pregnant women in a randomized controlled trial of CBT-I.

Methods
Participants were 87 pregnant women with insomnia disorder (mean age=32.5, SD=5.1 years) who were enrolled in a randomized controlled trial of CBT-I and were randomized to the CBT-I arm (5 sessions). We did not include women who did not complete treatment due to early labor. The Insomnia Severity Index (ISI) and Edinburgh Postnatal Depression Scale (EPDS) and demographic questionnaires (age, income, and educational background) were administered at screening.

Results
Logistic regression analyses were conducted to identify predictors of number of CBT-I sessions attended during pregnancy. A logistic regression model that included clinical predictors found that the ISI and EPDS were not significant predictors of session attendance. A logistic regression model that included demographic predictors (income, education, and age) was significant (F(3,76)=6.49, p&lt;0.001) with an R² of .204. Independently, income was not a significant predictor (β =.15, p=.32), but education (β =-.21, p&lt;.05) and age (β =-.48, p&lt;.01) were significant predictors of fewer sessions attended. Dropping income from the model, there was a significant age by education effect (β =1.39, p&lt;.05). Among participants with less than a college degree, those who were younger had attended fewer sessions during pregnancy. Among those who completed a college education and above, number of sessions attended did not differ by age.

Conclusion
Pregnant women with insomnia who were randomized to receive CBT-I were more likely to withdraw early from treatment if they were younger and had less than a college education. Further research that focuses on increasing attendance in CBT-I treatment among pregnant women needs to develop strategies to increase retention in this vulnerable population.

Support
NR013662