Obstructive Sleep Apnea Subjects Research Articles

T266M variants of ANGPTL4 improve lipid metabolism by modifying their binding affinity to acetyl-CoA carboxylase in obstructive sleep apnea

Background Angiopoietin-like protein 4 (ANGPTL4) is recognized as a crucial regulator in lipid metabolism. Acetyl-CoA carboxylases (ACACAs) play a role in the β-oxidation of fatty acids. Yet, the functions of ANGPTL4 and ACACA in dyslipidemia of obstructive sleep apnea (OSA) remain unclear. Methods This study included 125 male OSA subjects from the Shanghai Sleep Health Study (SSHS) who were matched for age, body mass index (BMI), and lipid profile. Serum ANGPTL4 levels were measured via ELISA. The ANGPTL4 T266M variants of 4455 subjects along with their anthropometric, fasting biochemical, and standard polysomnographic parameters were collected. Linear regression was used to analyze the associations between quantitative traits and ANGPTL4 T266M. Molecular docking and molecular dynamic simulation were employed to compare the effects of the wild-type ANGPTL4 and its T266M mutation on ACACA. Results Serum ANGPTL4 levels significantly decreased with increasing OSA severity (non-OSA: 59.6 ± 17.4 ng/mL, mild OSA: 50.0 ± 17.5 ng/mL, moderate OSA: 46.3 ± 15.5 ng/mL, severe OSA: 19.9 ± 14.3 ng/mL, respectively, p = 6.02 × 10−16). No associations were found between T266M and clinical characteristics. Molecular docking indicated that mutant ANGTPL4 T266M had stronger binding affinity for the ACACA protein, compared with wild-type ANGPTL4. In terms of protein secondary structure, mutant ANGTPL4 T266M demonstrated greater stability than wild-type ANGPTL4. Conclusions Serum ANGTPL4 levels were significantly decreased in OSA patients, particularly among individuals with severe OSA. Although functional ANGTPL4 T266M variants were not associated with lipid levels in OSA, ANGTPL4 T266M could enhance binding affinity for the ACACA protein, potentially regulating lipid metabolism.

Brain connectivity analysis based classification of obstructive sleep apnea using electroencephalogram signals

Obstructive sleep apnea (OSA) is a disorder which blocks the upper airway during sleep. The severity of OSA will lead heart attack, stroke and end of life. This proposed study explored the classification of OSA and healthy subjects using brain connectivity analysis from electroencephalogram (EEG) signals. Institute of System and Robotics—University of Coimbra (ISRUC) database were used for acquiring 50 EEG signals using 4 channels and noise removal has been accomplished by 50 Hz notch filter. The Institute of System and Robotics—University of Coimbra (ISRUC) database contained 50 EEG signals, with four channels, and a 50 Hz notch filter was applied to remove noise. Wavelet packet decomposition method was performing the segregation of EEG signals into five bands; Gamma (γ), beta (β), alpha (α), theta (θ) and delta (δ). A total of 4 electrode positions were used for the brain connectivity analysis for each EEG band. Pearson correlation method was effectively used for measuring the correlation between healthy and OSA subjects. The nodes and edges were highlighted the connection between brain and subjects. The highest correlation was achieved in delta band of OSA subjects which starts from 0.7331 to 0.9172 respectively. For healthy subjects, the positive correlation achieved was 0.6995. The delta band has been correlated well with brain when compared other bands. It has been noted that the positive correlation well associated with brain in OSA subjects, which classifies OSA from healthy subjects.

Ssleepnet: a structured sleep network for sleep staging based on sleep apnea severity

Sleep stage classification is essential in evaluating sleep quality. Sleep disorders disrupt the periodicity of sleep stages, especially the common obstructive sleep apnea (OSA). Many methods only consider how to effectively extract features from physiological signals to classify sleep stages, ignoring the impact of OSA on sleep staging. We propose a structured sleep staging network (SSleepNet) based on OSA to solve the above problem. This research focused on the effect of sleep apnea patients with different severity on sleep staging performance and how to reduce this effect. Considering that the transfer relationship between sleep stages of OSA subjects is different, SSleepNet learns comprehensive features and transfer relationships to improve the sleep staging performance. First, the network uses the multi-scale feature extraction (MSFE) module to learn rich features. Second, the network uses a structured learning module (SLM) to understand the transfer relationship between sleep stages, reducing the impact of OSA on sleep stages and making the network more universal. We validate the model on two datasets. The experimental results show that the detection accuracy can reach 84.6% on the Sleep-EDF-2013 dataset. The detection accuracy decreased slightly with the increase of OSA severity on the Sleep Heart Health Study (SHHS) dataset. The accuracy of healthy subjects to severe OSA subjects ranged from 79.8 to 78.4%, with a difference of only 1.4%. It shows that the SSleepNet can perform better sleep staging for healthy and OSA subjects.

Association of the TNF-α-308G>A gene polymorphism with left ventricular geometry and functional abnormalities in obstructive sleep apnea subjects.

Tumor necrosis factor-α (TNF-α) can induce left ventricular remodeling. In this study, we investigated whether the TNF-α-308G>A polymorphism is associated with left ventricular geometry (LVG) and left ventricular functional abnormalities in obstructive sleep apnea (OSA) subjects. Two hundred and seventy-eight subjects were enrolled. Echocardiography and genetic data were assessed in all patients. Geometric patterns of the left ventricle were determined from the relative wall thickness and left ventricular mass index (LVMI). Genetic analysis for the TNF-α-308G>A SNP rs1800629 was identified by Sanger sequencing. The correlations of the TNF-α-308G>A polymorphism with LVG and left ventricular function were analyzed by difference analysis and logistic regression. The chi-square test showed that there were differences in genotype distributions among the four groups (p = 0.033), such that the frequency of GA+AA genotypes was significantly higher in the concentric hypertrophy group than in the normal geometry group (p < 0.05). Independent sample T tests showed that the GA+AA genotypes had higher IVST, LVPWT, LVMI, E/e' values, and lower e' values than those of the GG genotype (p < 0.05). Logistic regression analysis showed that the TNF-α-308G>A polymorphism was independently correlated with eccentric hypertrophy (OR = 2.456, p = 0.047) and concentric hypertrophy (OR = 2.456, p = 0.047). In OSA patients, the TNF-α-308G>A polymorphism was linked to LVG and abnormal left ventricular diastolic function, suggesting that the TNF-α-308G>A polymorphism may have an important influence on LVG alterations.

Craniofacial features of adult obese obstructive sleep apnoea patients in relation to the obesity onset - A pilot study.

Obesity and craniofacial structures are aetiologies of obstructive sleep apnoea (OSA). The effect of obesity onset on the craniofacial development and growth of obese OSA subjects has been suggested, but supporting data were lacking. This study aimed to assess the craniofacial features of adult obese OSA patients in relation to their obesity onset. A total of 62 adult OSA patients were included in the study, consisting of 12 early-onset (i.e. before puberty), 21 late-onset (i.e. after puberty) and 29 non-obese. All participants underwent a sleep study and cephalometric radiograph. Cephalometric analysis was conducted to measure the craniofacial features among the groups. The early obesity onset group (n = 12) showed a more prognathic mandible, longer lower facial height, protrusive incisors, a more caudal position of the hyoid bone and a wider lower airway. The late-onset group (n = 21) had more proclined and protrusive upper incisors, a shallower overbite, a more inferiorly positioned hyoid bone and an obtuse craniocervical angle. The overall obese group showed a combination of the findings above, plus a shorter soft palate and shorter airway length. There was no significant difference between early and late obesity onset groups. However, the early group showed a tendency for a shallower or decreased mandibular plane angle and deeper overbite. The current pilot study had many limitations but holds important information as a hypothesis generator. Craniofacial features of OSA patients with different obesity onset showed discrepancies and were distinguished from non-obese controls. Adult OSA patients with an early obesity onset showed a tendency for a more hypodivergent growth pattern than those with a late obesity onset.

Opioid sensitivity in treated and untreated obstructive sleep apnoea: a prospective cohort study

BackgroundOpioid administration to patients with obstructive sleep apnoea (OSA) is controversial because they are believed to be more sensitive to opioids. However, objective data on opioid effects in OSA are lacking. We tested the hypothesis that subjects with untreated OSA have increased sensitivity to opioids compared with subjects without OSA, or with OSA treated with continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BIPAP). MethodsThis was a single-centre, prospective cohort study in subjects without OSA (n=20), with untreated OSA (n=33), or with treated OSA (n=21). OSA diagnosis was verified using type III (in-home) polysomnography. Subjects received a stepped-dose remifentanil infusion (target effect-site concentrations of 0.5, 1, 2, 3, 4 ng ml−1). Primary outcome was miosis (pupil area fractional change), the most sensitive opioid effect. Secondary outcomes were ventilatory rate, end-expired CO2, sedation, and thermal analgesia. ResultsThere were no differences in miosis between untreated OSA subjects (mean=0.51, 95% confidence interval [CI] 0.41–0.61) and subjects without OSA (mean=0.49, 95% CI 0.36–0.62) (mean difference=0.02, 95% CI −0.18 to 0.22); between treated OSA subjects (mean=0.56, 95% CI 0.43–0.68) and subjects without OSA (difference=0.07, 95% CI −0.16 to 0.29); or between untreated OSA and treated OSA (difference=−0.05, 95% CI −0.25 to 0.16). There were no significant differences between subjects without OSA, untreated OSA, and treated OSA in ventilatory rate, end-expired CO2, sedation, or thermal analgesia responses to remifentanil. There was no relationship between OSA severity and magnitude of opioid effects. ConclusionsNeither obstructive sleep apnoea nor obstructive sleep apnoea treatment affected sensitivity to the miotic, sedative, analgesic, or respiratory depressant effects of the opioid remifentanil in awake adults. These results challenge conventional notions of opioid effects in obstructive sleep apnoea. Clinical trial registrationNCT02898792 (clinicaltrials.gov).

Comparison of upper airway post oral appliance therapy in patients with obstructive sleep apnea using 3 different modalities (lateral cephalogram, acoustic pharyngometry and CBCT)- A prospective clinical study

Obstructive Sleep Apnea (OSA) is a condition that results due to partial or complete obstruction of airway when patient assumes a supine position and goes to sleep. of study was to compare the changes in upper airway resulting with oral appliance in treatment of OSA using lateral cephalogram, Acoustic Pharengometry (AP) and CBCT and correlate with AHI changes. OSA subjects treated with oral appliance therapy (OAT) had a significant improvement in upper airway diemensions. Study assessed the changes in upper airway following oral appliance for treatment of OSA using Lateral cephalogram, AP and CBCT and correlated the changes with AHI. The following conclusions can be drawn from this study (a)There is a marked improvement in mean volume, mean area and minimum distance of constriction in upper airway following OAT assessed using Lateral cephalogram, AP and CBCT. (b) Among the above 3 modalities, CBCT shows a statistically significant correlation with change in AHI following OAT.

Effect of depression on phase coherence between respiratory sinus arrhythmia and respiration during sleep in patients with obstructive sleep apnea.

Introduction: A high prevalence of major depressive disorder (MDD) among Obstructive Sleep Apnea (OSA) patients has been observed in both community and clinical populations. Due to the overlapping symptoms between both disorders, depression is usually misdiagnosed when correlated with OSA. Phase coherence between respiratory sinus arrhythmia (RSA) and respiration (λ RSA-RESP) has been proposed as an alternative measure for assessing vagal activity. Therefore, this study aims to investigate if there is any difference in λ RSA-RESP in OSA patients with and without MDD. Methods: Electrocardiograms (ECG) and breathing signals using overnight polysomnography were collected from 40 OSA subjects with MDD (OSAD+), 40 OSA subjects without MDD (OSAD-), and 38 control subjects (Controls) without MDD and OSA. The interbeat intervals (RRI) and respiratory movement were extracted from 5-min segments of ECG signals with a single apneic event during non-rapid eye movement (NREM) [353 segments] and rapid eye movement (REM) sleep stages [298 segments]. RR intervals (RRI) and respiration were resampled at 10 Hz, and the band passed filtered (0.10-0.4 Hz) before the Hilbert transform was used to extract instantaneous phases of the RSA and respiration. Subsequently, the λ RSA-RESP between RSA and Respiration and Heart Rate Variability (HRV) features were computed. Results: Our results showed that λ RSA-RESP was significantly increased in the OSAD+ group compared to OSAD- group during NREM and REM sleep. This increase was accompanied by a decrease in the low frequency (LF) component of HRV. Discussion: We report that the phase synchronization index between RSA and respiratory movement could provide a useful measure for evaluating depression in OSA patients. Our findings suggest that depression has lowered sympathetic activity when accompanied by OSA, allowing for stronger synchronization between RSA and respiration.

Retrospective Analysis of the Polysomnographic and Airway Changes in Obstructive Sleep Apnea (OSA) Subjects Who Underwent Maxillomandibular Advancement (MMA) Surgery

Retrospective Analysis of the Polysomnographic and Airway Changes in Obstructive Sleep Apnea (OSA) Subjects Who Underwent Maxillomandibular Advancement (MMA) Surgery

Revisiting the Epworth sleepiness scale : Is excessive daytime sleepiness still avalid screening tool for obstructive sleep apnea in apopulation at risk?

Obstructive sleep apnea (OSA) is acommon medical problem with numerous comorbidities and high costs. Since the introduction of the Epworth sleepiness scale (ESS), excessive daytime sleepiness (EDS) has been considered the most common and prominent symptom of OSA. Aim of this study was to re-evaluate the ESS for detection of OSA in apopulation at risk compared to the gold standard overnight polysomnography (PSG). A total of 266patients (mean age 57.9 ± 11.6 years; 189 men and 77women), referred to our sleep laboratory for probable OSA, were given ESS followed by an overnight PSG. The ESS values were compared to PSG apnea hypopnea index (AHI) with sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy (DA) calculated for ESS. The positive cut-off value for ESS was ≥ 10 and for AHI ≥ 5. Only 92(34.6%) subjects had a positive ESS. An OSA was diagnosed by PSG in 213 (80.1%) subjects: 46 having mild, 37 moderate and 130 severe apnea. Most subjects with positive ESS (88.0%) were found to have OSA but most subjects with a negative ESS (75.9%) were also positive for OSA (42% with AHI ≥ 30). The area under the receiver operating characteristic (ROC) curve for ESS was 0.60 (95% confidence interval, CI 0.54-0.66; p = 0.020) with SE 38.0%, SP 79.3%, PPV 88.0%, NPV 24.1% and DA 46.2%. It was found that excessive daytime sleepiness, measured by ESS, is not avaluable screening tool for OSA, especially when the test is negative. Other screening tests that involve additional parameters, beside daytime sleepiness alone, should be considered.

P.050 Effect of lemborexant on sleep architecture in adult and elderly subjects with mild to severe obstructive sleep apnea

Background: Obstructive sleep apnea (OSA) may be associated with sleep difficulties and decreased rapid eye movement (REM) sleep. Lemborexant (LEM), a dual-orexin-receptor-antagonist approved to treat adults with insomnia, increases total sleep time (TST) and REM sleep, and demonstrated respiratory safety in subjects with mild through severe OSA. Sleep architecture was thus analyzed after LEM treatment in those subjects. Methods: Studies E2006-A001-102 and E2006-A001-113 enrolled adults with mild (apnea-hypopnea index [AHI] ≥5 – &lt;15) or moderate (AHI ≥15 – &lt;30)/severe (AHI ≥30) OSA without insomnia. Subjects received LEM 10mg (LEM10) or placebo (PBO) in 2 treatment periods, Days 1 (D1) and 8 (D8), separated by ≥14 days. Least-squares-mean (minutes) for each sleep stage was compared. Treatment-emergent adverse events (TEAEs) were recorded. Results: Thirty-nine subjects with mild and 33 with moderate/severe OSA were randomized. On both days, TST was significantly higher in the LEM period for these subjects. Total non-REM on D1 in subjects with mild OSA and on both days in subjects with moderate/severe OSA were higher with LEM than PBO; REM also significantly increased in subjects with mild and moderate/severe OSA. Most TEAEs were mild. Conclusions: In OSA subjects without insomnia, LEM was associated with higher TST, non-REM, and REM versus PBO.

The use of the CT90 value in predicting anxiety in OSA: could it be a useful parameter?

Obstructive sleep apnea (OSA) is characterized by recurrent episodes of complete or partial obstruction of the upper airway leading to episodic desaturation. OSA patients often show symptoms of anxiety. Our study aimed to examine the presence and levels of anxiety in OSA and simple snoring relative to control subjects and to investigate the correlation between anxiety scores and polysomnographic, demographic, and sleepiness parameters.The study included 80 OSA, 30 simple snoring, and 98 control cases. Demographic, anxiety, and sleepiness data of all subjects were acquired. The Beck Anxiety Inventory (BAI) was used to determine the level of anxiety. The Epworth Sleepiness Scale (ESS) was used to evaluate the sleepiness level of participants. In addition, polysomnography recordings of those in the OSA and the simple snoring group were acquired.Significantly higher anxiety scores were found in patients with obstructive sleep apnea and simple snoring compared to the control group (p<0.01, p<0.01, respectively). From the polysomnographic data obtained from OSA and simple snoring subjects, the CT90 values (cumulative percentage of the time spent at saturations below 90%) and the AHI showed a weak positive correlation between the level of anxiety (p=0.004, r=0.271; p=0.04, r=0.196, respectively).Our study concluded that polysomnographic data showing the depth and duration of hypoxia may be more reliable in showing neuropsychological disorder and hypoxia-related comorbidities in OSA. The CT90 value can be used as a measure in the assessment of anxiety in OSA. Its advantage is that it can be measured with overnight pulse oximetry along with in-laboratory PSG and HSAT (home sleep apnea test).

P.047 Effect of lemborexant on sleep architecture in subjects with comorbid insomnia and mild obstructive sleep apnea from a phase 3 trial

Background: Lemborexant (LEM), a dual-orexin-receptor-antagonist approved to treat adults with insomnia, increases total sleep time (TST) and rapid eye movement (REM) sleep. Patients with obstructive sleep apnea (OSA) or co-morbid insomnia and OSA (COMISA) report sleeping difficulties and reduced REM, therefore sleep architecture was analyzed during LEM treatment. Methods: Study E2006-G000-304 (NCT02783729) was a 1-month, randomized, double-blind, placebo (PBO)- and active-comparator zolpidem-ER 6.25mg (ZOL)-controlled study in adults ≥55y with insomnia disorder. Subjects received PBO, LEM 5mg (LEM5), 10mg (LEM10), or ZOL. Least-square-mean duration of each sleep stage (minutes) was compared from pooled data on Nights (NT)1/2 and NT29/30 for mild OSA subjects (apnea hypopnea index ≥5 to &lt;15 events/h). Treatment-emergent adverse events (TEAEs) were recorded. Results: Of 409 subjects with mild OSA (LEM5=114/LEM10=105/ZOL=112/PBO=78) change from baseline (CFB) in TST and REM sleep was significantly larger with both LEM doses versus ZOL/PBO on both nights. CFB for total nonREM sleep was significantly higher (P&lt;0.0001) with both LEM doses versus PBO on both nights. LEM5 showed significantly higher (P&lt;0.05) nonREM sleep versus ZOL at NT29/30. Most TEAEs were mild/moderate. Conclusions: LEM significantly increased TST, REM, and nonREM sleep versus PBO in subjects with insomnia and mild OSA. Data support LEM treatment in the COMISA population.

0885 Alzheimer’s disease progression risk in Cognitive Normal Older Adults with Obstructive Sleep Apnea using NIA-AA Research Framework

Abstract Introduction We determined risk profiles of strata-specific cognitive-normal (NL) older-adults with obstructive sleep apnea (OSA) characterized by their Aβ, P-Tau &amp; T-tau (ATN) burden, on prospective AD stage-transition Methods Longitudinal study utilizing data from 167 community-dwelling NL older-adults participating in NYU studies on memory, sleep and aging. Subjects had baseline CSF AD-biomarker data and at least two follow-up clinical and neuropsychological data. OSA was defined using AHI4%. Using the NIA-AA Research Framework, data-driven, clinically relevant thresholds for CSF-Aβ42 (≤375pg/ml), P-tau (≥53.7pg/ml) and T-tau (≥367 pg/ml) indicated ATN status respectively. Twenty-four participants with suspected non-AD pathologic change defined as A-T+ were excluded leaving 143 for the analysis. Main outcome was AD stage-transition (i.e., change from Global Deterioration Scale (GDS) 1 or 2 [NL] at baseline to ≥3 [≥ MCI] during follow-up). Logistic mixed-effects models with random intercept and slope were used to assess associations between ATN characterized OSA subjects, and longitudinal AD stage transition, controlling for age-at-baseline, sex, APOE4-status, years-of-education, and their interactions with time. Results Of the 143 participants, 91 (63.8%) were women. The mean (SD) age was 69.6 (7.3) years and follow-up time was 4.73 (3.45) years. Sixteen (11.2%) were OSA+/A+/TN-, and 21 (14.7%) were OSA-/A+/TN-. Ninety-two (64.3%) had normal AD biomarkers (OSA+/A-/T- [n=45] and OSA-/A-/T- [N=47]). To generate strata-specific risks, subjects were combined into groups: (i) OSA subjects with AD pathologic change OSA+/A+/TN [n=25] consisting of OSA+/A+/TN+ [n=9] plus OSA+/A+/TN- [n=16] (ii) non-OSA subjects with AD pathologic change OSA-/A+/TN [n=26]) consisting of OSA-/A+/TN+ [n=5] and OSA-/A+/TN- [n=21] Fourteen subjects (9.8%) transitioned from NL to MCI (i.e., OSA+/A+/TN [6/25], OSA-/A+/TN [3/26], OSA+/A-/TN- [4/45] and OSA-/A-/TN- [3/47]). OSA+/A+/TN subjects were at higher risk of AD stage-transition relative to OSA-/A-/TN- (β = 1.31, 95%CI, 1.02, 1.62); OSA+/A-/TN- (β = 0.89, 95%CI, 0.42, 1.37); and OSA-/A+/TN subjects, (β = 0.71, 95%CI, 0.38, 1.04); P &amp;lt; .01 for all. OSA+/A-/T- vs. OSA-/A-/T- participants did not show differences in cognitive change over time (β = 0.22, 95%CI, -0.15, 0.39, P =.17). Conclusion Among ATN characterized NL older-adults with OSA, those with evidence of AD pathologic change have the greatest risk of developing AD. Support (if any) AASMBTS#231-BS-20, NIAK23AG068534A, AARG-D- 21-848397, BFFA2022033S

0739 Effect of Obstructive Sleep Apnea and Insomnia on Cognitive Impairment in World Trade Center (WTC) Responders

Abstract Introduction Mild Cognitive Impairment (MCI) is defined as a noticeable decline in cognitive abilities that doesn't interfere with daily activities; MCI may be a precursor of Alzheimer’s disease and related dementia. Elevated risk of MCI has been shown in subjects with obstructive sleep apnea (OSA) in a sleep clinic population and in subjects with insomnia in a general population. OSA and Insomnia both have a high prevalence among members of the World Trade Center Health Program General Responders’ Cohort (WTCHP GRC). Previous research indicated they had a high prevalence of MCI but did not examine sleep. We examined the association between MCI with OSA and/or Insomnia in the WTCHP GRC. Methods We assessed MCI by the Montreal Cognitive Assessment (MoCA) in English (n=115) and Spanish (n=27). MoCA &amp;lt; 26 defines MCI. OSA defined by AHI4&amp;gt;=5 or RDI&amp;gt;=15 events/hr, was assessed by home sleep test or in-lab NPSG. A score&amp;gt;7 on the Insomnia Severity Index (ISI) defined insomnia. Education was categorized as &amp;lt; or &amp;gt; bachelor’s (BA/BS) degree; subjects were categorized as Latino or not. Variables were analyzed using linear correlation, t-tests and chi-square tests as appropriate. Results The study population consisted of 142 subjects (80%M/20%F, age 58±8 years, BMI=29.7±5 kg/m2., Non-Latino/White=57%, Latino/any race=35%, &amp;lt; BA/BS=65%). OSA prevalence was 65.5% (mean AHI4=10.8±12.5/hr and RDI=21.42±16/hr). Insomnia prevalence was 48% (ISI=8.8 + 6). 48% (n=68) of subjects were classified as MCI. No correlation was observed between MoCA and OSA severity (r=0.1,p=0.24) or ISI (r=-0.1,p=0.1). Subjects without OSA had higher MCI prevalence (MCI_OSA=21.5% vs MCI_noOSA=37%, p=0.018). Lower educational level, race/ethnicity, and language (Spanish/English) (p&amp;lt; 0.001) were associated with MCI. Conclusion In this heterogenous cohort, we showed an unexpected lower MCI prevalence in OSA subjects. As shown by others, MCI defined by the MoCA was highly impacted by race/ethnicity, language and education. This suggests that our findings may be influenced by differences in the MoCA scoring and MCI cutoffs in Hispanic populations. To understand the relationship between MCI and sleep disorders in the WTC population, future studies should re-assess the cutoffs used in MoCA scoring or use tools to assess MCI less dependent on ethnicity and educational level. Support (if any) NIOSH/CDC U01OH011481, K24HL109156

0453 3-Year Outcomes of Proximal Hypoglossal Nerve Stimulation in the THN3 Controlled Trial

Abstract Introduction The THN3 randomized, controlled trial of moderate to severe obstructive sleep apnea (OSA) showed that proximal (“targeted”) hypoglossal nerve stimulation (HGNS) safely improved sleep-disordered breathing (SDB) and quality of life (QOL) through 11 months of treatment. Outcomes of subjects receiving active proximal HGNS also surpassed those with inactive therapy 4 months post-implant. Herein 3-year outcomes of THN3 are reported and compared to distal HGNS (STAR trial). Methods THN3 OSA subjects (Apnea-Hypopnea Index, AHI, 20-65/hr; BMI ≤ 35 kg/m2, no drug-induced sleep endoscopy screening) were followed long-term. Complete data through 3-year follow-up were analyzed. Efficacy measures comprised AHI, Oxygen Desaturation Index (ODI), %sleep time O2 saturation &amp;lt; 90% (T90), Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ) EQ-5D Visual Analog Scale (VAS) and Snore Outcomes Survey (SOS). 36-Month medians were compared against those after 11 months of therapy (Month 12/15) and with STAR. Adverse events (AEs) during Months 12-36 for THN3 and STAR were also compared. Results 75% of THN3 participants (104/138) attended 3-year follow-up, with complete efficacy records in N≥93 except for SOS (N=67, not administered at all sites). Proximal HGNS produced clinically and statistically significant improvements in SDB and QOL at Month 12/15 that were closely maintained at 36 Months (median paired changes at Month 36 from Baseline/Month 12/15: □AHI:-18.2/-0.1, □ODI:-16.2/0.8, □T90:-1.8/0.2, □FOSQ:3.0/0.0, □ESS:-5.0/0.0, □VAS:5.0/0.0, □SOS:37.5/3.1) and were comparable to STAR at 36 Months (□AHI:-19.4, □ODI:-17.2, □T90:-1.5, □FOSQ: 2.6, □ESS:-4.0). Procedure- and device-related AEs respectively totaled (3 and 27)/(4 and 122) in THN3/STAR over Months 12-36. During this time, 3 severe related-AEs occurred in THN3; the most frequent related AEs involved tongue discomfort (N=8, device-related). Conclusion Improvements in sleep apnea and QOL on proximal HGNS at Month 12/15 persisted through at least Month 36. Proximal HGNS long-term efficacy was comparable to distal HGNS. AEs occurred uncommonly during long-term follow-up and were typically mild. Proximal HGNS is a safe, effective, stable, long-term therapy, yielding comparable improvements to distal HGNS in treating moderate to severe OSA. Results of the ongoing, confirmatory OSPREY randomized controlled trial will provide additional insights into therapeutic benefits of proximal HGNS. Support (if any) LivaNova

0364 The Effect of Lemborexant on Polysomnographic Sleep Parameters in Adults with Mild, Moderate, or Severe Obstructive Sleep Apnea

Abstract Introduction Several commonly prescribed hypnotics may worsen respiratory function, especially in the elderly. Lemborexant (LEM) is a dual-orexin-receptor-antagonist approved to treat adults with insomnia. In Studies 102 (NCT03471871) and 113 (NCT04647383), LEM demonstrated respiratory safety in subjects with mild, moderate, or severe obstructive sleep apnea (OSA) who did not report insomnia. The current analyses evaluated sleep variables from these studies. Methods Studies 102 and 113 were double-blind, placebo (PBO)-controlled, crossover studies in adults with untreated mild (apnea-hypopnea-index [AHI] ≥5 to &amp;lt; 15), moderate (AHI≥15 to &amp;lt; 30), or severe (AHI≥30) OSA, without insomnia. Subjects were randomized to two 8-night periods (separated by ≥14 days) treated with LEM 10mg (LEM10) or PBO. Latency to persistent sleep (LPS), sleep efficiency (SE), and wake after sleep onset (WASO) were assessed using polysomnography on Days 1 (D1) and 8 (D8). Results The analysis set comprised 39, 13, and 20 subjects with mild, moderate, or severe OSA, respectively. On both days, LPS was not statistically different from PBO in any group. Compared with PBO, SE was significantly greater on D1 in subjects with mild (LEM10, 90.43; PBO, 80.31; P&amp;lt; 0.0001), moderate (LEM10, 88.83; PBO, 84.02; P=0.016), and severe (LEM10, 87.76; PBO, 77.84; P&amp;lt; 0.0001) OSA. On D8, SE was significantly greater in subjects with mild (LEM10, 86.65; PBO, 80.59; P=0.003) and moderate (LEM10, 88.45; PBO, 80.70; P=0.004) OSA, with a trend towards significance in subjects with severe (LEM10, 85.60; PBO, 80.63; P=0.055) OSA. WASO was significantly lower (improved) on D1 in subjects with mild (LEM10, 33.30; PBO, 76.76; P&amp;lt; 0.0001), moderate (LEM10, 44.26; PBO, 64.71; P=0.008), and severe (LEM10, 42.03; PBO, 91.49; P&amp;lt; 0.0001) OSA. On D8, WASO was significantly lower in subjects with mild (LEM10, 51.74; PBO, 70.52; P=0.015) and moderate (LEM10, 49.16; PBO, 75.15; P=0.008) but not severe (LEM10, 59.85; PBO, 74.46; P=0.161) OSA. LEM was well-tolerated. Conclusion In untreated OSA subjects without insomnia, irrespective of OSA severity, LEM improved sleep maintenance versus PBO. LPS did not differ between treatments since such patients may not report sleep onset difficulties. These findings support the use of LEM for patients with comorbid insomnia and sleep apnea (COMISA). Support (if any) Eisai, Inc.

0353 Effect of Lemborexant on Sleep Architecture in Adult and Elderly Subjects with Mild to Severe Obstructive Sleep Apnea

Abstract Introduction Lemborexant (LEM) is a dual-orexin-receptor antagonist approved to treat adults with insomnia. In such patients, LEM increased total sleep, with prominent increases in rapid eye movement (REM). Since patients with obstructive sleep apnea (OSA) may report sleep difficulties and show decreased REM sleep, sleep architecture was analyzed after treatment with LEM. Methods Studies 102 and 113 were double-blind, placebo (PBO)-controlled crossover studies in adult and elderly subjects with mild (apnea-hypopnea index [AHI] ≥5 to &amp;lt; 15) or moderate (AHI ≥15 to &amp;lt; 30)/severe (AHI ≥30) OSA, respectively, without insomnia. Subjects were randomized to LEM 10mg (LEM10) or PBO in two 8-night treatment periods (separated by ≥14 days). Least-squares-mean (LSM) for each sleep stage (minutes) was compared across conditions on Days 1 (D1) and 8 (D8). Treatment-emergent adverse events (TEAEs) were recorded. Results The analysis set comprised 39 subjects with mild OSA and 33 with moderate/severe OSA. On both days, total sleep time was significantly higher in the LEM condition in subjects with mild (D1: LEM10, 434.08; PBO, 385.46; P&amp;lt; 0.0001; D8: LEM10, 415.90; PBO, 386.85; P=0.003) and moderate/severe (D1: LEM10, 423.10; PBO, 385.48; P&amp;lt; 0.0001; D8: LEM10, 416.96; PBO, 385.57; P=0.001) OSA. Compared with PBO, total non-REM sleep significantly increased only on D1 in subjects with mild OSA (D1: LEM10, 330.57; PBO, 308.55; P=0.001; D8: LEM10, 323.77; PBO, 308.97; P=0.060) but on both days in subjects with moderate/severe OSA (D1: LEM10, 343.23; PBO, 327.45; P=0.006; D8: LEM10, 341.83; PBO, 322.48; P=0.018). Total REM sleep significantly increased in subjects with mild (D1: LEM10, 103.59; PBO, 76.91; P&amp;lt; 0.0001; D8: LEM10, 92.13; PBO, 77.93; P=0.004) and moderate/severe (D1: LEM10, 79.87; PBO, 58.03; P&amp;lt; 0.0001; D8: LEM10, 75.13; PBO, 62.69; P=0.006) OSA. REM latency was significantly decreased on both days in subjects with mild OSA (D1: LEM10, 51.96; PBO, 83.36; P&amp;lt; 0.0001; Day 8: LEM10, 67.52; PBO, 102.34; P=0.005) and only on D1 in subjects with moderate/severe OSA (D1: LEM10, 72.13; PBO, 98.90; P=0.029; D8: LEM10, 90.42; PBO, 106.63; P=0.242). LEM was well-tolerated; most TEAEs were mild. Conclusion In OSA subjects without insomnia, LEM nevertheless increased total sleep, non-REM, and REM sleep versus PBO. Support (if any) Eisai Inc.

0487 The effect of negative pressure ventilation on airflow in obstructive sleep apnea subjects undergoing drug induced sleep endoscopy

Abstract Introduction Drug induced sleep endoscopy (DISE) is used to visually characterize pharyngeal airway collapse in obstructive sleep apnea (OSA) to help determine appropriate patients for OSA surgery. The procedure has grown in complexity with the addition of airflow recording and continuous positive airway pressure (CPAP) titration to obtain additional measures of airway collapsibility. Lung volume can also influence airway collapse in OSA but is not evaluated as part of routine DISE. The purpose of this study is to characterize the relationship between changes in lung volume and upper airway collapse during DISE to gain further insight into factors contributing to airway collapse and their potential roles in influencing surgical decision making. Methods This study is an ongoing IRB approved prospective clinical trial assessing the effects of negative pressure ventilation on airway collapse during DISE. Enrolled patients first undergo DISE evaluation per clinical routine including a CPAP titration. CPAP is then held at a level where patients exhibit stable flow limitation. A negative pressure ventilator shell is placed over the torso of the body and negative pressures of up to -25cmH2O are applied to expand the chest and increase lung volume. Changes to nasal airflow and tidal volume are evaluated. The negative pressure ventilator is then released and changes to airflow back to baseline are recorded. Results Between 6/30/2022 and 11/30/2022, 5 patients completed the study. There were 4 men and 1 woman with an average age of 60 years, BMI of 26.67kg/m2, and apnea-hypopnea index (AHI) of 44.44 events/hr. Average peak inspiratory flow increased from 8.38L/min to 13.78L/min and average tidal volumes increased from 155mL to 269mL on negative pressure ventilation. Conclusion Increases in lung volume from negative pressure ventilation during DISE can improve airflow and tidal volume suggesting that changes in lung volume can influence the severity of upper airway collapse. Further study to better characterize this relationship can help add additional diagnostic information regarding airway collapse characteristics to provide better informed surgical decisions and develop new interventions. Support (if any) Supported by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) under Award Numbers UL1TR002378 and KL2TR002381

The relationship between obstructive sleep apnea and circulating tau levels: A meta-analysis.

Alzheimer's disease (AD) is an irreversible, progressive brain disorder that impairs memory, thinking, language, and, eventually, the ability to carry out the simplest of tasks. Tau protein, the major component of neurofibrillary tangles, is considered a key mediator of AD pathogenesis. The association between obstructive sleep apnea (OSA) and circulating tau remains unclear. The aim of the present meta-analysis was to evaluate the relationship between OSA and circulating tau via quantitative analysis. A systematic search of Pubmed, Embase, and Web of Science were performed. The mean values of circulating total tau (T-tau) and phosphorylated tau (P-tau) in OSA and control groups were extracted. Standardized mean difference (SMD) with 95% confidence interval (CI) was calculated by using a random-effect model or fixed-effect model. A total of seven studies comprising 233 controls and 306 OSA patients were included in this study. The meta-analysis showed that the circulating T-tau level was significantly higher in OSA patients than those in the control group (SMD=1.319, 95% CI=0.594 to 2.044, z=3.56, p<.001). OSA patients also had significantly higher circulating P-tau level than control group (SMD=0.343, 95% CI=0.122 to 0.564, z=3.04, p=.002). The present meta-analysis demonstrated that both circulating T-tau and P-tau levels were significantly increased in OSA subjects when compared with non-OSA subjects. Larger sample-size studies on the association between OSA and circulating tau are still required to further validate our results.