Obstructive Sleep Apnea Participants Research Articles

Acute Sleep Deprivation and Cerebral and Skeletal Muscle Oxygenation: A Review and Future Directions

Cerebral and skeletal muscle oxygenation are critical research areas for understanding blood flow and oxygen delivery during various physiological states, including cognitive tasks and exercise. Measuring oxygenated and deoxygenated hemoglobin through functional near-infrared spectrometry (fNIRS) enables non-invasive assessment of cerebral and skeletal muscle oxygenation. Research using fNIRS to explore oxygenation after sleep deprivation (SD) is limited and often contradictory. We reviewed how SD affects cerebral and muscle oxygenation as part of a broader review of how SD affects exercise through altered physiologic and perceptual responses. Herein, we consolidate existing knowledge, identify gaps, and suggest directions for future investigation. A comprehensive literature review was conducted via predefined search parameters using PubMed and Google Scholar, focusing on studies that employed fNIRS to measure cerebral and/or skeletal muscle oxygenation in humans after SD (total or partial) or in individuals with chronically fragmented sleep due to obstructive sleep apnea (OSA). Select studies report increased cerebral oxygenation post-SD, potentially due to compensatory mechanisms and increased brain activity. Contrarily, several studies indicate decreased cerebral oxygenation following SD, potentially due to impaired endothelial function, cortical neurovascular coupling, suppressed brain activity, or decreased oxygen consumption. Cerebral oxygenation may be associated with perceived exertion, suggesting meaningful links to exercise. Interestingly, exercise training may mitigate the effects of SD on oxygenation. The only study investigating skeletal muscle oxygenation with regards to sleep status found a lower tissue saturation index in OSA participants compared to controls, though hemoglobin parameters did not differ. The effect of SD on oxygenation remains equivocal, with no studies fully elucidating the mechanisms underlying these changes. This review is the foundation for an ongoing prospective study investigating the impact of acute SD on exercise capacity and fNIRS-derived cerebral and skeletal muscle oxygenation, with two participants enrolled to date and interim analyses planned at n=5 participants.

Obstructive Sleep Apnea is a Risk Factor for Incident COVID-19 Infection.

Cross-sectional studies suggest that obstructive sleep apnea (OSA) is a potential risk factor for incident COVID-19 infection, but longitudinal studies are lacking. In this study, two surveys from a large general population cohort, the COVID-19 Outbreak Public Evaluation (COPE) Initiative, undertaken 147 ± 58 days apart were analyzed to determine whether the pre-existing OSA was a risk factor for the incidence of COVID-19. Of the 24,803 respondents completing the initial survey, 14,950 were negative for COVID-19; data from the follow-up survey were available for 2,325 respondents. Those with incident COVID-19 infection had a slightly higher prevalence of OSA (14.3 vs. 11.5%, p=0.068). Stratification by treatment status revealed that those untreated for their OSA were at greater risk for developing COVID-19 infection (OSA Untreated, 14.2 vs. 7.4%, p≤0.05). In a logistic regression model adjusted for comorbidities, demographic and socioeconomic factors and the interaction between vaccination status and OSA, incident COVID-19 infection was 2.15 times more likely in those with untreated OSA (aOR: 2.15, 95% CI: 1.18-3.92, p≤0.05). Stratification by treatment status revealed only untreated OSA participants were at greater risk for COVID-19 (aOR: 3.21, 95% CI: 1.25-8.23, p≤0.05). The evidence from this study confirms untreated OSA as a risk factor for acquiring COVID-19 infection and highlights the importance of actively treating and managing OSA as a preventative mechanism against COVID-19 disease.

The effect of sleep position on sleep bruxism in adults with obstructive sleep apnea.

Most of the respiratory events in adults with obstructive sleep apnea (OSA) occurs in supine position. It has been reported that the contraction of masseter muscles is dependent on the occurrence of arousals rather than on the occurrence of respiratory events. This study had two aims: (1) to compare the rhythmic masticatory muscle activity (RMMA) index in supine position (RMMA_sup) and in non-supine positions (RMMA_nsup) in adults with OSA; and (2) to determine the associations between RMMA index in both supine position and non-supine positions on the one hand, and several demographic and polysomnographic variables on the other hand. One hundred OSA participants (36 females and 64 males; mean age = 50.3 years (SD = 10.5)) were selected randomly from among patients with a full-night polysomnographic recording. RMMA_sup index and RMMA_nsup index were compared using Mann-Whitney U-test. Multivariate linear regression analyses were used to predict RMMA index both in supine and non-supine positions based on several demographic and polysomnographic variables. In patients with OSA, the RMMA_sup index was significantly higher than the RMMA_nsup index (p < .001). RMMA_sup index was significantly associated with the arousal index (p = .002) and arousal index in supine position (p < .001). RMMA_nsup index was only significantly associated with the arousal index in non-supine positions (p = .004). Within the limitations of this study, RMMAs occur more frequently in supine position than in non-supine positions in patients with OSA. In both sleep positions, RMMAs are associated with arousals.

Heterogeneous Effects of Continuous Positive Airway Pressure in Non-Sleepy Obstructive Sleep Apnea on Cardiovascular Disease Outcomes: Post Hoc Machine Learning Analysis of the ISAACC Trial (ECSACT Study).

Rationale: Randomized controlled trials of continuous positive airway pressure (CPAP) therapy for cardiovascular disease (CVD) prevention among patients with obstructive sleep apnea (OSA) have been largely neutral. However, given that OSA is a heterogeneous disease, there may be unidentified subgroups demonstrating differential treatment effects. Objectives: We sought to apply a novel data-drive approach to identify nonsleepy OSA subgroups with heterogeneous effects of CPAP on CVD outcomes within the Impact of Sleep Apnea Syndrome in the Evolution of Acute Coronary Syndrome (ISAACC) study. Methods: Participants were randomly partitioned into two datasets. One for training (70%) our machine-learning model and a second (30%) for validation of significant findings. Model-based recursive partitioning was applied to identify subgroups with heterogeneous treatment effects. Survival analysis was conducted to compare treatment (CPAP vs. usual care [UC]) outcomes within subgroups. Results: A total of 1,224 nonsleepy OSA participants were included. Of 55 features entered into our model, only two appeared in the final model (i.e., average OSA event duration and hypercholesterolemia). Among participants at or below the model-derived average event duration threshold (19.5 s), CPAP was protective for a composite of CVD events (training hazard ratio [HR], 0.46; P = 0.002). For those with longer event duration (>19.5 s), an additional split occurred by hypercholesterolemia status. Among participants with longer event duration and hypercholesterolemia, CPAP resulted in more CVD events compared with UC (training HR, 2.24; P = 0.011). The point estimate for this harmful signal was also replicated in the testing dataset (HR, 1.83; P = 0.118). Conclusions: We discovered subgroups of nonsleepy OSA participants within the ISAACC study with heterogeneous effects of CPAP. Among the training dataset, those with longer OSA event duration and hypercholesterolemia had nearly 2.5 times more CVD events with CPAP compared with UC, whereas those with shorter OSA event duration had roughly half the rate of CVD events if randomized to CPAP.

The relationship between obstructive sleep apnea and osteoarthritis: evidence from an observational and Mendelian randomization study.

Obstructive sleep apnea (OSA) and osteoarthritis (OA) are common comorbidities that significantly impact individuals' quality of life. However, the relationship between OSA and OA remains unclear. This study aims to explore the connection between OSA and OA and evaluate causality using Mendelian randomization (MR). A total of 12,454 participants from the National Health and Nutrition Examination Survey (2009-2012) were included. OSA participants were identified based on self-reported interviews. The association between OA and OSA was assessed through multivariable logistic regression analysis. A two-sample MR was employed to investigate the relationship between OSA and OA, specifically hip OA and knee OA, utilizing the inverse variance-weighted (IVW) approach. Based on the observational study, individuals with OSA exhibited a higher risk of OA (OR = 1.67, 95% CI = 1.40-1.98). IVW demonstrated that the risk of OA (OR = 1.13, 95% CI: 1.05-1.21, p = 0.001), hip OA (OR = 1.11, 95% CI: 1.04-1.18, p = 0.002), and knee OA (OR = 1.08, 95% CI: 1.02-1.14, p = 0.005) was significantly associated with OSA. Reverse MR analyses indicated no effect of OA on OSA. Additionally, body mass index (BMI) was found to mediate 36.9% (95% CI, 4.64-73.2%, p = 0.026) of the OSA effects on OA risk. The cross-sectional observational analysis unveiled noteworthy associations between OSA and OA. Meanwhile, findings from the MR study provide support for a causal role.

Clinical features of sleep apnea syndrome and cognitive impairment in multiple sclerosis

Background: Complications of obstructive sleep apnea (OSA) have been reported in patients with multiple sclerosis (MS). Patients with sleep apnea syndrome (SAS) due to OSA also show cognitive decline, with similar clinical characteristics to that manifested in MS. SAS due to OSA is a treatable condition, and the associated cognitive decline is expected to improve. This study investigates clinical features of SAS in people living with MS and contribute to improve cognitive dysfunction of MS.Methods: A case-control study was conducted. Cognitive functions were evaluated by the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test 2 (PASAT-2) and 3 (PASAT-3). The Respiratory Event Index (REI) was measured using Out of Center Sleep Testing (OCST). We defined subjects with REI ≥ 5 as OSA and divided participants into two groups with or without SAS due to OSA. Cognitive and respiratory characteristics were statistically compared between patients with MS and healthy controls.Results: We enrolled 67 people living with MS and 31 age- and sex-matched controls. OCST detected OSA in people living with MS and controls, and the prevalence rates were 28.4 % and 25.8 %, respectively. REI values (5.2 ± 7.9 vs 3.9 ± 5.2, p = 0.509) and number of participants with REI ≥ 5 (19 vs 8, p = 0.793) were similar between the MS and control group. The SDMT, PASAT-2, and PASAT-3 scores were significantly lower in the MS group than the control group (p < 0.001, p = 0.001, and p < 0.001, respectively). The interaction effect of MS and SAS on cognitive function was not significant in the SDMT (p = 0.078), but in the PASAT-2 (p = 0.043) and PASAT-3 (p = 0.020).Conclusion: This study revealed the prevalence rates of SAS in Japanese people living with MS and the usefulness of OCST for detection of SAS. This study also revealed that concomitant SAS can facilitate cognitive decline in people living with MS. These findings suggest that an appropriate intervention for OSA can be beneficial for people living with MS with cognitive decline.

Regional associations between inspiratory tongue dilatory movement and genioglossus activity during wakefulness in people with obstructive sleep apnoea.

Inspiratory tongue dilatory movement is believed to be mediated via changes in neural drive to genioglossus. However, this has not been studied during quiet breathing in humans. Therefore, this study investigated this relationship and its potential role in obstructive sleep apnoea (OSA). During awake supine quiet nasal breathing, inspiratory tongue dilatory movement, quantified with tagged magnetic resonance imaging, and inspiratory phasic genioglossus EMG normalised to maximum EMG were measured in nine controls [apnoea-hypopnea index (AHI) ≤5 events/h] and 37 people with untreated OSA (AHI >5 events/h). Measurements were obtained for 156 neuromuscular compartments (85%). Analysis was adjusted for nadir epiglottic pressure during inspiration. Only for 106 compartments (68%) was a larger anterior (dilatory) movement associated with a higher phasic EMG [mixed linear regression, beta=0.089, 95% CI [0.000, 0.178], t(99)=1.995, P=0.049, hereafter EMG↗/mvt↗]. For the remaining 50 (32%) compartments, a larger dilatory movement was associated with a lower phasic EMG [mixed linear regression, beta=-0.123, 95% CI [-0.224, -0.022], t(43)=-2.458, P=0.018, hereafter EMG↘/mvt↗]. OSA participants had a higher odds of having at least one decoupled EMG↘/mvt↗ compartment (binary logistic regression, odds ratio [95% CI]: 7.53 [1.19, 47.47] (P=0.032). Dilatory tongue movement was minimal (>1 mm) in nearly all participants with only EMG↗/mvt↗ compartments (86%, 18/21). These results demonstrate that upper airway dilatory mechanics cannot be predicted from genioglossus EMG, particularly in people with OSA. Tongue movement associated with minimal genioglossus activity suggests co-activation of other airway dilator muscles. KEY POINTS: Inspiratory tongue movement is thought to be mediated through changes in genioglossus activity. However, it is unknown if this relationship is altered by obstructive sleep apnoea (OSA). During awake supine quiet nasal breathing, inspiratory tongue movement, quantified with tagged magnetic resonance imaging (MRI), and inspiratory phasic genioglossus EMG normalised to maximum EMG were measured in four tongue compartments of people with and without OSA. Larger tongue anterior (dilatory) movement was associated with higher phasic genioglossus EMG for 68% of compartments. OSA participants had an ∼7-times higher odds of having at least one compartment for which a larger anterior tongue movement was not associated with a higher phasic EMG than controls. Therefore, higher genioglossus phasic EMG does not consistently translate into tongue dilatory movement, particularly in people with OSA. Large dilatory tongue movements can occur despite minimal genioglossus inspiratory activity, suggesting co-activation of other pharyngeal muscles.

Association of serum uric acid with all-cause and cardiovascular mortality in obstructive sleep apnea

The study investigated the association between Serum Uric Acid (SUA) levels and all-cause as well as cardiovascular mortality in patients with Obstructive Sleep Apnea (OSA). This prospective cohort study enrolled participants with OSA from four cycles of the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2008, and 2015–2018. A weighted Cox proportional hazards model was used to assess adjusted hazard ratios (aHRs) and their corresponding 95% confidence intervals (CI) for all-cause and cardiovascular mortality. Additionally, multivariable logistic regression and restricted cubic splines (RCS) models were employed to examine nonlinear relationships between SUA and all-cause and cardiovascular mortality. Among the 5,584 OSA participants included in the study, covering the four NHANES cycles and with a median follow-up of 4.333 years, a total of 537 deaths were observed, including 108 deaths attributed to cardiovascular disease. Comparing the fourth quartile (Q4) of uric acid levels, both the fifth quartile (Q5) (aHRs = 1.51, 95% CI [1.08, 2.12]) and the second quartile (Q2) (aHRs = 1.53, 95% CI [1.04, 2.25]) of uric acid levels were independently associated with an increased risk of all-cause mortality. Furthermore, comparing the fourth quartile (Q4) of uric acid levels, the second quartile (Q2) (aHRs = 2.40, 95% CI [1.08, 5.35]) of uric acid levels were independently associated with an increased risk of cardiovascular mortality. The RCS model demonstrated a U-shaped pattern in the association between SUA and all-cause mortality in OSA, with an inflection point observed at 5.83 mg/dl. The findings of this study suggest a U-shaped association between serum SUA levels and all-cause mortality and nonlinearity association between serum SUA levels and all-cause mortality. Further studies are warranted to determine the causal relationship between SUA levels and all-cause and cardiovascular mortality.

Associations Between Amyloid Burden, Hypoxemia, Sleep Architecture, and Cognition in Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is associated with an increased risk of amyloid-β (Aβ) burden, the hallmark of Alzheimer's disease, and cognitive decline. To determine the differential impacts of hypoxemia and slow-wave sleep disruption on brain amyloid burden, and to explore the effects of hypoxemia, slow-wave sleep disruption, and amyloid burden on cognition in individuals with and without OSA. Thirty-four individuals with confirmed OSA (mean±SD age 57.5±4.1 years; 19 males) and 12 healthy controls (58.5±4.2 years; 6 males) underwent a clinical polysomnogram, a NAV4694 positron emission tomography (PET) scan for Aβ burden, assessment of APOEɛ status and cognitive assessments. Linear hierarchical regressions were conducted to determine the contributions of demographic and sleep variables on amyloid burden and cognition. Aβ burden was associated with nocturnal hypoxemia, and impaired verbal episodic memory, autobiographical memory and set shifting. Hypoxemia was correlated with impaired autobiographical memory, and only set shifting performance remained significantly associated with Aβ burden when controlling for sleep variables. Nocturnal hypoxemia was related to brain Aβ burden in this sample of OSA participants. Aβ burden and hypoxemia had differential impacts on cognition. This study reveals aspects of sleep disturbance in OSA that are most strongly associated with brain Aβ burden and poor cognition, which are markers of early Alzheimer's disease. These findings add weight to the possibility that hypoxemia may be causally related to the development of dementia; however, whether they may be a therapeutic target for dementia prevention in OSA is yet to be determined.

Improved depressive symptoms, and emotional regulation and reactivity, in individuals with obstructive sleep apnea after short- and long-term CPAP therapy use

Obstructive Sleep Apnoea (OSA) is associated with high rates of depression; however, if and how treatment of OSA improves depressive symptoms is unclear. To further understand this link we considered the role of emotional regulation – the ability to control and express our emotional responses – thought to be a central component of depression. This study aimed to assess changes in depressive symptoms and emotional responses in individuals with OSA after 4- and 12-months of continuous positive airway pressure (CPAP) treatment. One-hundred and twenty-one OSA participants (50 female, Mage = 51.93; mean AHI = 36.27) were recruited from a tertiary clinical sleep service prior to CPAP initiation, and randomised to either a CPAP group or a 4 month wait-list group. Participants completed the Center for Epidemiological Studies Depression Scale, the Emotional Reactivity Scale and the Difficulties in Emotion Regulation Scale at baseline, and 1-, 2-, and 4-months follow-up. The CPAP group also completed the questionnaires 12-months after CPAP initiation. CPAP use at 1 month and 12 months was 5.1h/night and 4.9h/night, respectively. Significant improvements in depressive symptoms, emotional regulation and reactivity, and subjective sleepiness were observed after 4 months in both groups, however, the within group changes were only significant for those using CPAP. After 12-months of CPAP treatment, these improvements were maintained. There was no association between CPAP treatment adherence and improvements in any outcome. CPAP treatment for 12 months may reduce symptoms of depression and improve emotional regulation in individuals with OSA.

Single-centre, single-blinded, randomised, parallel group, feasibility study protocol investigating if mandibular advancement device treatment for obstructive sleep apnoea can reduce nocturnal gastro-oesophageal reflux (MAD-Reflux trial)

IntroductionJust under half of patients with obstructive sleep apnoea (OSA) also have gastro-oesophageal reflux disease (GORD). These conditions appear to be inter-related and continual positive airway pressure (CPAP) therapy, the...

Comparison of efficacy and usability of custom mandibular advancement devices fabricated with the conventional method and digital workflow: A pilot clinical study.

To compare the effects of fabricating methods of custom monoblock mandibular advancement devices (MADs) on usability and efficacy in patients with mild and moderate obstructive sleep apnea (OSA). Digitally fabricated custom MADs (dMADs) were produced for 11 OSA participants who had previously used conventionally fabricated custom MADs (cMADs). The participants answered a modified usability questionnaire for both MADs, and the average scores that were given to the questionnaire were evaluated by age, sex, and body mass index (BMI), and the scores of cMADs and dMADs were compared. After 6 months of usage of each MAD, the apnea-hypopnea index (AHI), mean and lowest oxygen saturations, and total sleep time were measured for efficacy assessment. Data were analyzed with Cronbach's alpha, Mann-Whitney U, Kruskal-Wallis, Wilcoxon signed-rank, one-way repeated measures analyses of variance, and Bonferroni tests (α = 0.05). Cronbach's alpha was found at 0.834 and 0.722 for the conventional and digital questionnaires, respectively. The usability scores of the dMADs were significantly higher than those of cMADs (p = 0.013). There was no difference in usability scores in terms of sex or BMI (p>0.05). No statistically significant difference was found for cMAD (p = 0.113) among age groups; however, there was a significant difference for dMAD (p = 0.046). The AHI, mean, and lowest oxygen saturation values were significantly affected by MAD usage (p<0.001). However, total sleep time values did not differ after the MAD treatments (p>0.05). Significantly lower AHI and significantly higher lowest oxygen saturation values were observed with dMAD, while both appliances led to similar results for mean oxygen saturation and total sleep time values (p>0.05). Participant usability scores were higher for digitally manufactured MADs than conventionally manufactured MADs. However, both conventional and digital MADs were found effective in decreasing the AHI levels and increasing the mean and lowest oxygen saturation values of the participants.

Association of Perceived Stress Scale with the Severity of Obstructive Sleep Apnea in Pakistani Population

Background: Obstructive Sleep Apnea (OSA) is a prevalent sleep disorder characterized by recurrent episodes of partial or complete upper airway obstruction during sleep, leading to disruptions in breathing patterns and, consequently, reduced oxygen level. OSA has traditionally been viewed as a sleep-related physiological disorder, there is growing recognition that psychological factors, such as stress, may play a role in its onset and progression. Objective: To evaluate the association of Perceived Stress Scale with the severity of Obstructive Sleep Apnea in Pakistani Population. Study Design: Prospective cross-sectional study. Settings: untreated OSA individuals at Pulmonary Vascular and Sleep Disorders division of Dow University Hospital in Karachi, Pakistan. Duration: Study was done during a period of six months from May 2022 to October 2022. Methods: Patients OSA diagnosis through overnight Polysomnography with AHI of more than 5, and OSA participants above 18 years of age were included. A stress questionnaire was filled out when the individual came for overnight Polysomnography. The Sleep technologist measures the anthropometric measurements like height, and weight through height scales and weight machines, the neck circumference through the inch tape, BMI was computed through a formula which is weight in kg/height in meter2, and stress was evaluated through the Perceived Stress Scale (PSS). Data analysis was performed by using IBM SPSS statistics 26. Results: A total of 167 OSA patients participated in the study. There were 100 (60%) male and 67 (40%) female individuals. The mean age of females who perceived stress was 53.7 ± 10.5years which is higher from males 47.9 ± 13.1 years. Low stress was found in moderate and severe OSA as compare to mild OSA, similarly 49% moderate stress in Moderate OSA and 52% moderate stress in Severe OSA patients respectively. The percentage of high stress was significantly prominent in Mild OSA in comparison to Moderate and Severe OSA. The result of the study shows that the perceived stress scale is significantly correlated with Obstructive sleep apnea (p&lt;0.001). Conclusion: The outcomes of this study reveal a direct significant correlation between OSA and the Perceived Stress Scale. The findings underscore the importance of ongoing investigation to delve into potential underlying mechanisms.

0563 The Evaluation of a Revolutionary Custom-Made Oral Appliance Design on Effectiveness, Efficacy, and Compliance

Abstract Introduction Evaluate the clinical effectiveness of the SomnoDent Avant with Bflex technology, a custom-made oral appliance therapy (OAT) device in the treatment of mild/moderate Obstructive Sleep Apnea (OSA) for naïve and PAP non-compliant patients. Hypothesis for the study was that the unique strap mechanism design of the appliance encouraged mouth closure and nasal breathing, would have high levels of effectiveness, particularly for supine sleepers. The evaluation of the initial fit of the device as well as patient’s and bed partner’s acceptance were also investigated Methods Prospective 90 day trial, participants age ≥ 18 with AHI of ≥10 to ≤30 events/hr. confirmed by using a WatchPAT, Home Sleep Apnea Testing (HSAT) device at baseline. Initial advancement of the lower jaw was 60%. Treatment effectiveness is derived from two endpoints: efficacy and compliance. The efficacy of the OAT is defined as the change from baseline in AHI, based on one and three-month HSAT. Efficacy was measured in supine, lateral and prone positions. Compliance data was obtained from the Dentitrac (BRAEBON Medical Corporation) chip embedded in the SomnoDent Avant device looking at usage for at least 4 hours per night for at least 5 out of 7 nights a week. Results Preliminary data from 50 participants (66% male, 35% female), age: 52.3 ± 11.8 yrs., BMI: 31.1. A statistically significant 3-month trend change from baseline AHI -11.0 ± 7 (37/37), Average usage:7.0hrs/night, ESS: 3 month change from baseline -3.3 ± 4.0 (80.0% improvement), FOSQ 10: 1.7 ± 2.2 (76.7% improvement). Adequate (first-time) fit of the device upon initial insertion 89.3%, bed partner sleep improvement 83.3%, and 88.9% would recommend the use of the Avant OAT device. Conclusion • SomnoDent Avant demonstrated high effectiveness in the treatment of OSA, particularly with supine dependent OSA participants. The unique design of the Avant strap likely acts to close the patient’s mouth, encouraging nasal breathing • Statistical improvement in the quality of life • Optimum first-time fit • Improvement in bed partner quality of sleep Support (if any) SomnoMed

Depression with obstructive sleep apnea lead to high cardiovascular disease morbidity/all-cause mortality: Findings from the SHHS cohort.

The aim of this study is to explore the association between depression and obstructive sleep apnea, and cardiovascular disease morbidity/all-cause mortality using Sleep Heart Health Study data. This post hoc analysis of a prospective study used patient data from the Sleep Heart Health Study conducted between 1995 and 1998. The association between depression and obstructive sleep apnea, and cardiovascular disease morbidity/all-cause mortality was explored using multivariable Cox proportional hazard models. A total of 4918 participants, 656 (13.3%) with obstructive sleep apnea (obstructive sleep apnea group), 1614 (32.8%) with depression (depression group), 482 (9.8%) with depression and obstructive sleep apnea (depression and obstructive sleep apnea group), and 2166 (44%) with neither obstructive sleep apnea nor depression (health group), were included. The incidence of cardiovascular disease was 24.5%, 31.0%, 31.6% and 41.7% for healthy, depression, obstructive sleep apnea, and depression and obstructive sleep apnea groups, respectively. The risk of cardiovascular disease in depression and obstructive sleep apnea participants was increased compared with that in healthy participants, which was consistent across various definitions of obstructive sleep apnea (hazard ratio [95% confidence interval]: 1.24 [1.06-1.47]; 1.25 [1.05-1.49]; 1.28 [1.06-1.54]; 1.55 [1.22-1.96] for apnea-hypopnea index ≥ 10 per hr, 15 per hr, 20 per hr, 30 per hr, respectively). The risk of all-cause mortality was increased in the depression and obstructive sleep apnea participants (hazard ratio: 1.46; 95% confidence interval: 1.07-1.99) compared with that in healthy participants when the definition of obstructive sleep apnea was apnea-hypopnea index ≥ 30. Participants with depression and obstructive sleep apnea might be at a greater risk of cardiovascular disease, and those with higher apnea-hypopnea index might be at a greater risk of all-cause mortality.

Longitudinal medial temporal lobe gray matter volume and cognitive changes in late middle‐aged and older adults with treated and non‐treated obstructive sleep apnea

AbstractBackgroundNeuroimaging studies in obstructive sleep apnea (OSA) have found both gray matter atrophy and hypertrophy in medial temporal lobe subregions, the latter probably reflecting edema. Whether and how these changes progress over time when OSA is treated or untreated remains unclear. Here, we investigated gray matter volume changes in medial temporal lobe subregions in treated OSA, untreated OSA and control participants aged &gt; 55 years. We also explored whether the medial temporal lobe volume at baseline could predict cognitive decline.MethodTwenty‐three non‐treated OSA participants (65.8 ±5.4 years) and twenty controls (64.0 ±6.4 years) were evaluated with overnight polysomnography, MRI session and neuropsychological assessment. Twelve OSA participants then started continuous positive airway pressure (CPAP) therapy and used it at least 4 hours per night, 4 nights per week. Eleven participants refused treatment. Participants were evaluated again with MRI and neuropsychology after 18 months. We extracted the entorhinal, hippocampal and parahippocampal volumes using FreeSurfer 7.1. We performed repeated‐measure ANOVAs with Group (treated OSA, untreated OSA and controls) and Time (baseline and follow‐up) on bilateral volumes. We also performed partial correlations between bilateral medial temporal volumes at baseline and changes in cognition (Montreal Cognitive Assessment, score at follow‐up – baseline) in each group separately. Analyses were corrected for age, sex, and total intracranial volume.ResultWe found a significant Group X Time interaction for bilateral parahippocampal volumes (F = 7.2; p = 0.002) where treated OSA participants showed a decreased volume over time (p tukey&lt;0.001), while no changes occurred in the two other groups. Regarding the predictive value of medial temporal lobe volume, in untreated participants, higher bilateral hippocampal volume at baseline was associated with more severe cognitive decline over time (r = ‐0.77; p = 0.01). In treated participants, higher bilateral entorhinal cortex volume at baseline was associated with more cognitive decline (r = ‐0.74; p = 0.035). No associations were found in controls.ConclusionThese preliminary results showed that presenting hypertrophy of the medial temporal lobe subregions at baseline is associated with worse cognitive outcome at 18‐month follow‐up in OSA participants. In the CPAP group, the decrease in parahippocampal volume might represent a reduction in hypertrophy, possibly by limiting edema.

Abstract 13856: Ventricular Remodeling and the Effect of Continuous Positive Airway Pressure in Patients With Combined Diabetes Mellitus and Obstructive Sleep Apnea: A Secondary Analysis of a Randomized Clinical Trial

Introduction: Type 2 diabetes mellitus (T2DM) and obstructive sleep apnea (OSA) are independently associated with adverse left (LV) and right (RV) ventricular remodeling. However, the effect of continuous positive airway pressure (CPAP) is unknown. Hypothesis: CPAP prevents adverse remodeling in T2DM+OSA overlap. Methods: In this prospective study, 141 participants (Control: 28; T2DM only: 27; OSA only: 29; T2DM+OSA: 57) were recruited and underwent home sleep testing and cardiac magnetic resonance. Subsequently, 53 adults from the T2DM+OSA group were enrolled in a 3-month, parallel-arm, randomized, placebo-controlled trial comparing active and sham CPAP. The measures of interest were LV and RV remodeling indices (mass/volume). Kruskal-Wallis for multiple groups and Wilcoxon rank-sum and signed-rank tests for paired samples for two groups were applied. Results: Groups were of similar sex [Control (males): 54%; T2DM: 44%; OSA only: 52%; T2DM+OSA: 65%; p=0.31)]; OSA and T2DM+OSA participants were older (age in years: 46± 15; 51±7.8; 53±10; 56±9.1* # ; respectively p=0.001; *p&lt;0.05 vs. control, # p&lt;0.05 vs. T2DM only) and had higher BMI (29.8±6.3; 31±4.8; 34±6.3*; 35.2±6.6* # kg/m 2 , respectively p=0.001). At baseline, LV remodeling index (g/ml) was higher in T2DM+OSA (0.67±0.12; 0.71±0.10; 0.75±0.13; 0.78±0.16*; respectively, p=0.01), whereas RV remodeling index was similar (0.19±0.03; 0.20±0.03; 0.20±0.03; 0.21±0.04; p=0.33). The difference in LV remodeling index persisted after adjustment for age, sex and BMI (p&lt;0.001). CPAP treatment over 3 months prevented progression of adverse LV remodeling compared with sham [difference: CPAP: -0.01 (-0.08, 0.08) g/ml; sham: 0.11 (-0.03, 0.17) g/ml; p=0.03)] but not of RV remodeling index [difference: CPAP: 0.01 (-0.04, 0.08) g/ml; sham: 0.003 (-0.02, 0.04) g/ml; p=0.82)]. Conclusion: T2DM and OSA increased adverse LV but not RV remodeling. CPAP prevented the progression of adverse LV but not RV remodeling.

Sleep apnea and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA): leveraging state-of-the-art vascular imaging.

To further characterize the relationship between obstructive sleep apnea (OSA) and carotid atherosclerosis, we examined the structural and metabolic features of carotid plaque using hybrid 18-F-fluorodeoxyglucose (FDG) Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) in the Multi-Ethnic Study of Atherosclerosis (MESA). We studied 46 individuals from the MESA-PET and MESA-Sleep ancillary studies. OSA was defined as an apnea hypopnea index [AHI] ≥ 15 events per hour (4% desaturation). PET/MRI was used to measure carotid plaque inflammation (using target-to-background-ratios [TBR]) and carotid wall thickness (CWT). Linear regression was used to assess the associations between OSA, CWT and TBR. The mean age was 67.9years (SD 8.53) and the mean BMI was 28.9kg/m2 (SD 4.47). There was a trend toward a higher mean CWT in the OSA (n = 11) vs. non-OSA group (n = 35), 1.51 vs. 1.41 (p = 0.098). TBR did not differ by OSA groups, and there was no significant association between OSA and carotid plaque inflammation (TBR) in adjusted analyses. Although there was a significant interaction between OSA and obesity, there were no statistically significant associations between OSA and vascular inflammation in stratified analysis by obesity. Despite a trend toward a higher carotid wall thickness in OSA vs. non-OSA participants, we did not find an independent association between OSA and carotid plaque inflammation using PET/MRI in MESA. Our findings suggest that simultaneous assessments of structural and metabolic features of atherosclerosis may fill current knowledge gaps pertaining to the influence of OSA on atherosclerosis prevalence and progression.

Deep Learning Analyses of Brain MRI to Identify Sustained Attention Deficit in Treated Obstructive Sleep Apnea: A Pilot Study.

Persistent sustained attention deficit (SAD) after continuous positive airway pressure (CPAP) treatment is a source of quality of life and occupational impairment in obstructive sleep apnea (OSA). However, persistent SAD is difficult to predict in patients initiated on CPAP treatment. We performed secondary analyses of brain magnetic resonance (MR) images in treated OSA participants, using deep learning, to predict SAD. 26 middle-aged men with CPAP use of more than 6 hours daily and MR imaging were included. SAD was defined by psychomotor vigilance task lapses of more than 2. 17 participants had SAD and 9 were without SAD. A Convolutional Neural Network (CNN) model was used for classifying the MR images into +SAD and -SAD categories. The CNN model achieved an accuracy of 97.02±0.80% in classifying MR images into +SAD and -SAD categories. Assuming a threshold of 90% probability for the MR image being correctly classified, the model provided a participant-level accuracy of 99.11±0.55% and a stable image level accuracy of 97.45±0.63%. Deep learning methods, such as the proposed CNN model, can accurately predict persistent SAD based on MR images. Further replication of these findings will allow early initiation of adjunctive pharmacologic treatment in high-risk patients, along with CPAP, to improve quality of life and occupational fitness. Future augmentation of this approach with explainable artificial intelligence methods may elucidate the neuroanatomical areas underlying persistent SAD to provide mechanistic insights and novel therapeutic targets.

Pharyngeal enlargement via tongue advancement differs with mandibular advancement therapy response and improves treatment prediction

Abstract Introduction Mandibular advancement splint (MAS) treatment outcome prediction for obstructive sleep apnoea (OSA) is currently unreliable. Lower baseline AHI has been associated with better MAS response but is a poor predictor on its own. Imaging markers may enhance prediction. We investigate how the upper airway enlarges via posterior tongue advancement, using tagged MRI during mandibular advancement, as a potential predictor of MAS treatment response. Methods 101 untreated OSA participants (AHI 10–102 events/hr) underwent an MRI scan wearing a MAS. Mid-sagittal tagged MRI images were collected to quantify tongue movement during passive jaw advancement. Upper airway cross-sectional areas were measured with the mandible in a neutral position and advanced to 70% of the maximum protrusion. Treatment outcome was determined after a minimum of 9 weeks of therapy. Results 71 participants completed the study: 33 were responders (AHI&amp;lt;5 or AHI≤10 events/hr with &amp;gt;50% AHI reduction), 11 were partial responders (&amp;gt;50% AHI reduction but AHI&amp;gt;10 events/hr), and 27 non-responders (AHI reduction&amp;lt;50% and AHI≥10 events/hr). Responders had the greatest naso- and oropharyngeal tongue advancement (0.40±0.08 and 0.47±0.13mm, respectively) and oropharynx enlargement (6.41±2.12%) per millimetre of mandibular advancement. The inclusion of these imaging markers along with baseline AHI in a multivariate model classified more patients in the right MAS response group (69.2%) than a model based only on baseline AHI (50.0%) when the mandible was advanced by at least 4 mm. Conclusions Tongue advancement and upper airway enlargement with mandibular advancement in conjunction with baseline AHI improves MAS treatment response categorisation to a satisfactory level.