bluuebunny/crossref_metadata_2025_split huggingface dataset:
0461 Parietal EEG Slow Activity During NREM Is Associated with Overnight Spatial Memory Performance in CPAP-treated OSA
Authors: Mullins Anna , Parekh Ankit , Kam Korey , Valencia Daphne , Wickramaratne Sajila , Ayappa Indu , Rapoport David , Varga Andrew 
Published: April 2024

Abstract

Introduction
Sleep disturbance from obstructive sleep apnea (OSA) impairs overnight memory processing which may be mediated by changes to slow wave sleep. Indeed, reduced region-specific EEG slow activity during non-REM sleep has been associated with worse overnight declarative, motor and spatial memory. Using a polysomnologically (PSG)-verified model of SWS-specific CPAP-withdrawal to create three conditions of 1) stable-SWS on CPAP, 2) SWS-fragmentation with intermittent hypoxemia (OSAsws), and 3) SWS-fragmentation with reduced hypoxemia (OSAsws+O2), we investigated whether CPAP withdrawal during SWS induces acute changes in EEG slow wave activity that is associated with overnight spatial navigational memory performance.

Methods
19 channel EEG, re-referenced to average mastoids from 72 PSGs in 24 CPAP-adherent patients (7 female, average age 56yrs) with moderate-to-severe OSA was inspected visually for artifact removal prior to analysis using an automatic algorithm (DETOKS) for detection of relative slow wave (0.5-4Hz, SWA) and slow oscillation (0.6-1Hz, SOA) activity. During each PSG visit, participants explored one of three 3D maze environments, performing 3 timed trials before and after each of 3 randomized and counterbalanced SWS disruption conditions, 1)CPAP, 2)OSASWS & 3)OSASWS+O2. Frontal (Fz), central (Cz) and parietal (Pz) relative SWA, SOA and overnight change in maze completion times were compared according to PSG condition using Friedman Rank Sum and Conover’s tests. The relationship between SWA and maze performance was tested using Pearson’s correlation coefficient.

Results
No significant differences were observed between the three conditions for non-REM EEG slow activities or overnight change in maze completion times. In the CPAP condition only, greater EEG slow activity at Pz (SWA, r=0.57, p=0.01 and SOA, r=0.67, p=0.002) was associated with larger improvements in overnight maze completion times.

Conclusion
EEG slow wave activity and maze performance were not influenced by the recapitulation of OSA during SWS in CPAP-treated individuals. There was, however, a positive relationship between parietal-specific EEG slow oscillation activity and overnight maze performance during stable CPAP-treated slow wave sleep. These observations suggest that OSA of sufficient severity to impact SWA or SOA may negatively impact spatial navigational memory, but the selective withdrawal of CPAP in SWS only was not sufficient to do so.

Support (if any)
R01AG056682,R21OH012623,K24HL109156
0463 Sleep Disruption and Longitudinal Cognitive Aging
Authors: Khazaie Sepideh , Bena James , Ryan Delaney , Pao Winnie , Mehra Reena 
Published: April 2024

Abstract

Introduction
Aging is often accompanied by sleep disturbances and cognitive impairment. However, the relationship between specific sleep parameters and cognitive decline remains unclear. This study investigates the longitudinal association of objective measures of sleep disruption including sleep architecture and hypoxia in relation to levels of cognitive function, as ascertained by the Montreal Cognitive Assessment (MoCA) scores. We hypothesize that certain sleep characteristics, including degree of hypoxia, significantly influence cognitive aging trajectories.

Methods
This study involved an analysis of patients with mild cognitive impairment (MCI) in Alzheimer's Disease (AD) between 2011 and 2023. The main predictor variables were various sleep study parameters, including the Apnea-Hypopnea Index (AHI), mean SpO2 levels, arousal index, and sleep stage percentages. Covariates in the analysis were sex and age. To assess cognitive function, we used the MoCA which is a comprehensive tool scoring (range 0-30; assesses visuospatial, executive function, memory, attention, etc.), where higher scores indicate better cognitive function. Our statistical approach involved multivariable linear mixed models, adjusted for the covariates, to evaluate the MoCA scores over time (-1 to +3 years from sleep study) with sleep parameters.

Results
The study included 275 patients with MCI-AD, across 816 observations with an average age of 69.6 ± 8.7 years. Among them, 65.1% were male, 85.1% white with median 16 (IQR:12-17) years of education. Over 21 months mean follow-up among those with repeat MoCA testing, scores declined by -0.06 points/month (95% CI -0.08, -0.04; p&lt; 0.001). A significant finding was the association of higher mean oxygen saturation with a more rapid cognitive decline, at -0.10 points per month for each 1% increase in oxygen levels (95% CI -0.19, -0.01; p=0.033). Other sleep measures including sleep architecture showed no significant associations with MoCA score changes.

Conclusion
This study sheds light on the intricate relationship between sleep quality, oxygen saturation, and cognitive aging. Our findings reveal a novel association between higher sleep-related oxygen saturation levels and accelerated cognitive decline in MCI-AD patients is biologically plausible given reports of altered EEG activity with task-evoked potentials in response to hyperoxia. Future investigation should clarify effects of hyperoxia on neural activity and oxidative stress in neurodegeneration.

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0465 Increased All-cause Mortality and Associated Factors in Korean OSA Patients
Authors: Seo Won Woo , Seo Mincheol , Shin Jiyoon , Lee Kyung Hwa , Jeon Jeong Eun , Lee Ha Young , Yoo Jin Hyuk , Kim Sun-Young , Lee Yu Jin 
Published: April 2024

Abstract

Introduction
Obstructive sleep apnea (OSA) has been known to be associated with increased cardiovascular, metabolic diseases and mortality. As few studies reported associated factors on relationship between OSA and mortality, we aimed to investigate all-cause mortality and associated factors in OSA patients.

Methods
We performed retrospective study in group of 1547 subjects who referred to the Center for Sleep and Chronobiology, Seoul National University Hospital, from June 2004 to December 2013. Subjects who had other sleep disorders including parasomnia, restless legs syndrome, possible periodic limb movement disorder (PLMI&gt;15), narcolepsy, etc were excluded (N=331) and a total of 1216 subjects was included for analysis. Deaths out of final subjects that occurred up to December 31, 2020 from Statistics of Korea, the national bureau of statistics were examined. We divided subjects into four groups: no-sleep disorder (N=276, AHI&lt; 5), mild (N=268, 5≤AHI&lt; 15), moderate (N=275, 15≤AHI&lt; 30) and severe OSA groups (N=397, AHI≥30). We employed cox proportional hazard regression analysis to estimate hazard ratios (HRs) against no-sleep disorder and 95% confidence intervals adjusted for age, sex, hypertension, diabetes, dyslipidemia and longest apnea duration on polysomnography.

Results
HR of all-cause mortality was increased in the severe, moderate and mild OSA groups (HR=5.515, 95% CI=1.337-22.425, p-value=0.017, HR=5.443, 95% CI=1.555-19.054, p-value=0.008, HR=4.179, 95% CI=1.305-13.382, p-value=0.016, respectively). Longest apnea duration showed a significant association with decreased mortality (HR=0.955, 95% CI=0.932-0.979, p-value&lt; 0.001). Age was associated with increased mortality (HR=1.103, 95% CI=1.071-1.136, p-value&lt; 0.001). However, sex, diabetes, hypertension and dyslipidemia showed no significant association with mortality (All p-values &gt; 0.05).

Conclusion
Current results suggest increased mortality in patients with OSA. In particular, severity of OSA based on AHI was related with increased mortality. We found longest apnea duration was associated with decreased mortality as well. Previous notion on adverse effect of shorter apnea duration associated with frequent arousal might attribute to these results. Since CPAP compliance was not considered in this study, association between CPAP use and apnea duration also can be considered as another possible cause. We need further study to confirm the associated factors on mortality in OSA including apnea duration.

Support (if any)
National Research Foundation (RS-2023-00242754).
0467 Effect of Hypoxia on Ventilatory Responsiveness in Opioid-Related Sleep Disordered Breathing
Authors: Rastogi Ruchi , Greig Danny , Johnston Ian , Miryala Chandra , Mishra Poonam , Zhao Lili , Badr M Safwan , Chowdhuri Susmita 
Published: April 2024

Abstract

Introduction
Ventilatory control mechanisms mediating opioid-associated sleep disordered breathing (SDB) are unclear, with reduced hypoxic ventilatory response (HVR) observed acutely with opioids, but increased HVR with chronic methadone use. Increased chemoresponsiveness may contribute to breathing instability during sleep. Aim: Determine the effects of chronic oral prescription opioids on HVR in individuals with opioid-associated SDB. Hypothesis: Compared to controls without opioid use, individuals with chronic prescription opioids-associated SDB will have increased HVR during wakefulness.

Methods
We studied 5 males on prescription opioids with SDB (age: 55±15 years, BMI: 33±7 kg/m2, apnea hypopnea index (AHI): 30±24/hr; CAI 3±6/hr, morphine equivalent dose: 31±12 mg , serum opiate levels: 23±22 ng/ml), and 5 control males with SDB, not on opioids, (age: 48±11 years, BMI: 28±2 kg/m2, AHI 37±15/hr, CAI 0.2±0.5/hr; urine drug screen negative for opioids). Opioid-SDB and controls underwent multiple trials with exposure to 2-minute episodes of isocapnic hypoxia (Hypoxia PetO2: 5-7%), each trial interspersed with room air, during wakefulness. Isocapnia was maintained by bleeding in CO2. Number of hypoxia (Hx) trials: opioid-SDB: 8.2±1.3; controls 7.0±0.7. All ventilatory parameters were analyzed breath by breath. For each trial, the ventilatory parameters during hypoxic exposure were compared with the room air baseline period immediately preceding the exposure. HVR was calculated as the change in minute ventilation during nadir hypoxia compared to control breaths for a corresponding change in PetO2.

Results
Minute ventilation (VI) during hypoxia trial was 99.1±28.5% of baseline Vi in opioid-SDB vs. 105±16% baseline Vi in control participants. The coefficient of variation of Vi was 29% in opioid-SDB vs. 15% in control-SDB (p=0.05). Opioid-SDB: PetCO2 37±4 mmHg at baseline and 37±3 mmHg during Hx trials; Control: PetCO2 37±4 mmHg at baseline and 41±3 during Hx trials. Opioid-SDB: PetO2 100±6 mmHg at baseline and 33±6 mmHg during Hx trials; Control: PetO2 101±5 mmHg at baseline and 46±7 during Hx trials. HVR: 0.6±2.4 L/min/mmHg vs. 1.4±4.2 L/min/mmHg in opioid-SDB vs. controls.

Conclusion
HVR tended to be reduced in opioid-SDB vs. controls during wakefulness. There was variability in minute ventilation in opioid users. Additional studies in a larger sample are required to delineate hypoxic ventilatory responsiveness in opioid-SDB.

Support (if any)
VHA CSR&D:1I01CX001938-02A0
0469 On-road Driving Performance the Morning After Bedtime Seltorexant in Major Depressive Disorder and Healthy Elderly
Authors: Devineni Damayanthi , Li Lingjue , Zhou Xianhuang , Pinter Christine , Flossbach Yanina , Pandina Gahan , Buntinx Erik 
Published: April 2024

Abstract

Introduction
Seltorexant, a potent and selective orexin-2 receptor antagonist is being developed as an adjunctive treatment for major depressive disorder (MDD). On-road driving performance was evaluated in adults and elderly with MDD taking an antidepressant (SSRI/SNRI) and in healthy elderly participants following bedtime administration of seltorexant.

Methods
This was a randomized, double-blind, placebo- and positive-controlled 4 way crossover study in 37 adults with MDD taking an antidepressant (SSRI/SNRI) and 26 elderly participants (n=19 with MDD; n=7 healthy). Study treatments were administered at bedtime for eight consecutive days: 2 dose levels of seltorexant (20-or 40-mg), zopiclone 7.5-mg on Days 1 and 8, or placebo. Driving performance was assessed on days 2 and 9 (9h post-dose) using a 1-hour standardized highway driving test (~100 km) in normal traffic, measuring standard deviation of lateral position (SDLP, weaving of car). Drug–placebo difference in SDLP of ≥2.4 cm was considered to reflect clinically meaningful driving impairment.

Results
Mean SDLP differences between drug and placebo following seltorexant 20-mg and 40-mg on days 2 and 9 were very small and the upper limits of the 2-sided 95%CI were below the threshold of 2.4 cm (least-square mean [95%CI] 20 mg: −0.1 [−0.80, 0.57] cm, Day 2; −0.2 [−0.81, 0.46], Day 9; 40-mg: 0.4 [−0.27, 1.12], Day 2; 0.6 [−0.14, 1.25], Day 9), suggesting no clinically relevant changes in driving performance in adults and elderly with MDD. Similar results for SDLP were noted for other populations (adults with MDD, elderly, all participants). Assay sensitivity was demonstrated using the positive control, zopiclone, which caused impaired on-road driving performance as measured by the SDLP (least-square mean [95%CI] Day 2: 2.8 [1.99, 3.59] cm, Day 9: 2.7 [1.76, 3.60] cm; lower limits of the 2-sided 95% CI were &gt;0 cm). Most TEAEs were mild or moderate in severity and no new safety issues emerged.

Conclusion
Seltorexant 20-mg and 40-mg administered as single and multiple doses had no clinically meaningful negative effects on next morning driving performance in adults and elderly with MDD taking an antidepressant (SSRI/SNRI) and healthy elderly participants as assessed by mean changes in SDLP relative to placebo.

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0471 Simplified Endotyping Using Home Sleep Study Data to Inform Targeted Therapy for Obstructive Sleep Apnea
Authors: Eckert Danny , Dutta Ritaban , Levendowski Daniel 
Published: April 2024

Abstract

Introduction
Obstructive sleep apnea (OSA) pathogenesis is heterogenous with important contributions from at least 4 key endotypes: 1) impaired pharyngeal anatomy, 2) unstable breathing control (high loop gain), 3) poor pharyngeal dilator muscle responsiveness and 4) waking up too easily to minor airway narrowing (low respiratory arousal threshold). Gold standard physiology assessments in a relatively small number of well-characterized participants indicate wide interindividual variability in pharyngeal collapsibility (impaired upper airway anatomy) and that ~30% of people with OSA have impairment in each of the three non-anatomical endotypes. Overall, ~70% have impairment in one or more non-anatomical endotypes which has implications for targeted therapy decisions. We recently developed a simplified model to estimate OSA endotypes from standard in-laboratory polysomnography and clinical data (Dutta et al, Annals ATS, 2021). In this study, we applied this model to estimate OSA endotypes in a large clinical population.

Methods
OSA endotypes were estimated using standard sleep study outputs and clinical data (i.e., age and BMI) from &gt;6,500 consecutive home-based diagnostic studies (Sleep Profiler PSG- Advanced Brain Monitoring). All participants had an apnea/hypopnea index (AHI) &gt;5 events/h. The proportion of participants who were estimated to have impairment in one or more OSA endotypes was calculated according to previously published physiological cutoffs.

Results
On average, participants (39% female) had moderately severe OSA (AHI=28±23 events/h ([Mean±SD]), were middle aged (49±15 years) and obese (BMI=32±7 kg/m2). 29% were estimated to have only mild anatomical compromise (Pcrit&lt; -2cmH2O). 23% had poor dilator muscles, 31% high loop gain and 29% had a low arousal threshold. 62% of participants had impairment in one or more non-anatomical endotypes.

Conclusion
These data highlight the feasibility for simplified OSA endotyping using home sleep study recordings at scale. In addition, consistent with smaller, more detailed physiology studies, a substantial proportion of the clinical OSA patient population have only minor anatomical impairment. Furthermore, approximately two thirds have impairment in one or more non-anatomical endotypes. These findings highlight the potential for simplified OSA endotyping to inform targeted non-CPAP therapy selection for a large proportion of people diagnosed with OSA.

Support (if any)
DJE is funded by a National Health and Medical Research Investigator Grant (1196261).
0473 Homocysteine as a Predictor of Apnea-hypopnea Index in Obstructive Sleep Apnea: Longitudinal Epidemiological Study
Authors: Morelhão Priscila , Cavalcante-Silva Vanessa , Fernandes Guilherme , D'Almeida Vania , Tufik Sergio , Andersen Monica 
Published: April 2024

Abstract

Introduction
Obstructive sleep apnea (OSA) affects nearly 1 billion people globally, and has established links with cardiovascular and neurocognitive complications. Although it has some limitations, the apnea-hypopnea index (AHI) is commonly used to gauge OSA severity and therapeutic response. Our objective was to investigate homocysteine (Hcy) levels as a predictor of AHI values and as a risk factor for OSA.

Methods
This is a prospective longitudinal cohort study with 8 years follow-up based on a subsample of the São Paulo Epidemiological Sleep Study (EPISONO). Data from polysomnography and blood analysis were used, data from the AHI and plasma Hcy, cobalamin and folic acid levels were extracted from dataset. The generalized estimation equation was used to estimate the predictive value of Hcy levels, and logistic regression was performed to estimate the risk.

Results
Our findings showed that Hcy was a predictor for an increased AHI, and AHI increased over time. Individuals with plasma Hcy levels ≥15 µmol/L experienced an average AHI increase of 7.43 events/hour ([beta coefficient] β=7.43; 95%CI: 2.73 to 12.13) over time, compared to those with plasma levels &lt; 10 µmol/L. A similar trend was apparent in those with plasma Hcy levels between 10≥ to &lt; 15 µmol/L, who had an AHI increase with an average beta coefficient of 3.20 events/hour (95%CI:1.01 to 5.39) compared to those with plasma Hcy levels &lt; 10µmol/L. Our results revealed that increased plasma Hcy levels could be considered a risk factor for the development of OSA. Those with higher plasma Hcy levels have a greater risk of developing OSA (odds ratio=1.098 95%CI: 1.022 to 1.181).

Conclusion
In conclusion, the results suggest that plasma Hcy levels can predict the severity of OSA, highlighting their association with AHI.

Support (if any)
This study was supported by the Associação Fundo de Incentivo à Pesquisa (AFIP), São Paulo, Brazil. MLA and VDA are recipients of CNPq fellowships. MLA is supported by the São Paulo Research Foundation (FAPESP #2020/13467-8).
0474 The Impact of Neck Circumference and Body Mass Index on Upper Airway Collapsibility
Authors: Hutz Michael , Patel Harsh , Chapman Thomas , Whitehead Russell , Zhang Yanyu 
Published: April 2024

Abstract

Introduction
Drug-induced sleep endoscopy (DISE) is the most commonly utilized diagnostic tool for determining sites of upper airway collapse in patients with obstructive sleep apnea (OSA) seeking alternative treatments to continuous positive airway pressure (CPAP). Drug-induced sleep endoscopy with positive airway pressure (DISE-PAP) is a new technique that allows for both the qualitative visualization of upper airway collapse as well as a quantitative measure of collapsibility. In this study, we sought to determine if the anatomic features of neck circumference and body mass index (BMI) impact the degree of upper airway collapsibility, also known as the pharyngeal opening pressure (PhOP), during DISE-PAP.

Methods
This was a retrospective, consecutive cohort study of adult sleep surgery patients referred to a CPAP-alternatives clinic and evaluated by a single, experienced sleep surgeon at a tertiary care center from July 2021 to September 2023. Inclusion criteria were adults greater than 18 years of age with a history of OSA (apnea hypopnea index &gt; 5) and a history of CPAP-intolerance. All patients underwent DISE-PAP in a standardized fashion as previously described by the senior author. The primary outcome sought to determine the relationship between neck circumference and the degree of upper airway collapsibility (PhOP), while the secondary outcome evaluated the relationship between BMI and PhOP.

Results
97 patients were included for neck circumference and 264 patients were included in analysis of BMI. On average, the cohort was middle-aged, obese (BMI 30.3), male (70.5%), White (64.8%), and with moderate-severe obstructive sleep apnea (AHI 33.3). In terms of our primary hypothesis, a mild positive correlation was observed between neck circumference and PhOP (Spearman correlation coefficient = 0.310, p = .002). In regards to our secondary hypothesis, a mild positive correlation was observed between BMI and PhOP (Spearman correlation coefficient = 0.237, p = 0.0001).

Conclusion
This study found a weak but statistically significant correlation between both neck circumference and BMI and the degree of upper airway collapsibility. These findings contribute to the current understanding of the impact on neck circumference and BMI on OSA. Further research is required to determine the clinical impact of these outcomes in the management of CPAP-intolerant patients.

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0475 Differences and Risk Factors Related to Hypoxic Burden in Non-Hispanic Black/African and White Older Adults
Authors: Cesar Justin Oliver , Figueredo Luisa , Arthur Matthew , Sogade Anamarie , Weisgerber Elizabeth , Gonzalez Moses , Gills Joshua L , Bernard Mark A , Parekh Ankit , Williams Natasha , Jean-Louis Girardin , Osorio Ricardo , Bubu Omonigho 
Published: April 2024

Abstract

Introduction
Obstructive Sleep Apnea (OSA) is as a prevalent sleep-related breathing disorder. The apnea-hypopnea index (AHI), used for the diagnosis of OSA, captures only the frequency of respiratory events and has demonstrable limitations. Measurements such as total arterial oxygen saturation &lt; 90% (T90) and Hypoxic Burden (HB) have demonstrated utility for predicting cardiometabolic diseases, and other adverse health outcomes. Additionally, OSA has been associated with differential effects across racial/ethnic categories. In this cross-sectional study, we evaluate a community-dwelling healthy cohort of non-Hispanic Black and White older adults participating in studies on sleep, memory, and aging.

Methods
The study included a two-day clinical visit evaluation and one-night polysomnogram (PSG). Hypoxic burden was calculated as the area between the baseline and the SpO2 trace for any episode with &gt;= 3% desaturation. Black and White older adults were relatively matched by age, gender, BMI and AHI4%. Multiple regression analyses with HB as the dependent variable and Age, Race, Sex, HTN, AHI4%, and BMI as the independent variables, and t-test was performed for group comparisons with a p-value &lt; 0.05 defined as significant.

Results
Of the 140 subjects, 88 (62.85%) were females, 52 (37.15%) were males, 70 (50%) were non-Hispanic Black, and 70 (50%) were non-Hispanic White. The mean age was 67 (CI=63-71) years, BMI was 25 (CI=23-32) kg/m**2, and education was 16 (CI=14-18) years. Overall, male subjects had higher HB compared to females, p&lt;.001. A significant difference in the HB was observed between blacks and whites regardless of hypertensive status, p&lt;.008 for all. Black males and females had higher HB than white males and females, respectively, p&lt;.0009 for all. Furthermore, age was negatively correlated with HB and this correlation was stronger in blacks compared to whites (r=-.43 vs. r=-.38, p&lt;.05).

Conclusion
Hypoxic burden is a better predictor of cardio metabolic effects, compared to the AHI. Our findings indicate a more pronounced impact, particularly among blacks, with factors such as sex, hypertension, and BMI influencing this association. Future studies should examine the effects of modifiable factors, and how these may contribute to these observed sex/racial differences.

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