Impairment In Obstructive Sleep Apnea Research Articles

Shedding light on neurofilament involvement in cognitive decline in obstructive sleep apnea and its possible role as a biomarker.

Obstructive sleep apnea is one of the most common sleep disorders with a high estimated global prevalence and a large number of associated comorbidities in general as well as specific neuropsychiatric complications such as cognitive impairment. The complex pathogenesis and effects of the disorder including chronic intermittent hypoxia and sleep fragmentation may lead to enhanced neuronal damage, thereby contributing to neuropsychiatric pathologies. Obstructive sleep apnea has been described as an independent risk factor for several neurodegenerative diseases, including Alzheimer's disease and all-cause dementia. The influence of obstructive sleep apnea on cognitive deficits is still a topic of recent debate, and several mechanisms, including neurodegeneration and depression-related cognitive dysfunction, underlying this correlation are taken into consideration. The differentiation between both pathomechanisms of cognitive impairment in obstructive sleep apnea is a complex clinical issue, requiring the use of multiple and costly diagnostic methods. The studies conducted on neuroprotection biomarkers, such as brain-derived neurotrophic factors and neurofilaments, are recently gaining ground in the topic of cognition assessment in obstructive sleep apnea patients. Neurofilaments as neuron-specific cytoskeletal proteins could be useful non-invasive indicators of brain conditions and neurodegeneration, which already are observed in many neurological diseases leading to cognitive deficits. Additionally, neurofilaments play an important role as a biomarker in other sleep disorders such as insomnia. Thus, this review summarizes the current knowledge on the involvement of neurofilaments in cognitive decline and neurodegeneration in obstructive sleep apnea patients as well as discusses its possible role as a biomarker of these changes.

Brainstem impairment in obstructive sleep apnoea and the effect of CPAP treatment: an electrophysiological blink reflex study

PurposeThis study aimed to evaluate the functionality of the brainstem structures through the blink reflex (BR) test in patients with obstructive sleep apnoea (OSA) and to assess the effects of continuous positive airway pressure (CPAP) treatment on BR responses.MethodsPatients with moderate-severe OSA and controls underwent BR testing. Patients with OSA who were adherent to CPAP therapy repeated BR testing at 6 months follow-up. CPAP adherence was defined as CPAP use for ≥ 4 hour per night on > 5 nights per week with residual apnoea-hypopnea index less than 5 events per hour.ResultsA total of 22 patients with OSA (86% male, mean age 57.8 ± 10.6 years) and 20 controls (60% male, mean age 55.3 ± 9.3 years) were included. Patients with OSA showed longer right and left R1 latency, as well as delayed right ipsilateral and contralateral R2 latencies compared to controls. Patients with OSA who were compliant with CPAP treatment (n = 16; 88% men, mean age 58.8 ± 9.7 years) showed a significant decrease in latency of the right ipsilateral and contralateral R2 responses at 6 months.ConclusionThis study showed an abnormal pattern of BR responses in patients with OSA, consistent with a significant impairment of brainstem functionality in OSA. CPAP treatment partially improved the BR responses, suggesting the importance of treating OSA.

Summary of drug therapy to treat cognitive impairment-induced obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a severe sleep disorder associated with intermittent hypoxia and sleep fragmentation. Cognitive impairment is a signifi- cant and common OSA complication often described in such patients. The most commonly utilized methods in clinical OSA treatment are oral appliances and continuous positive airway pressure (CPAP). However, the current therapeutic methods for improving cognitive function could not achieve the expected efficacy in same patients. Therefore, further understanding the molecular mechanism behind cognitive dysfunction in OSA disease will provide new treatment methods and targets. This review briefly summarized the clinical manifestations of cognitive impairment in OSA disease. Moreover, the pathophysiological molecular mechanism of OSA was outlined. Our study concluded that both SF and IH could induce cognitive impairment by multiple signaling pathways, such as oxidative stress activation, inflammation, and apoptosis. However, there is a lack of effective drug therapy for cognitive impairment in OSA. Finally, the therapeutic potential of some novel compounds and herbal medicine was evaluated on attenuating cognitive impairment based on certain preclinical studies.

Brain morphology and functional connectivity alterations in patients with severe obstructive sleep apnea

BackgroundIt has been demonstrated that widespread structural and functional brain alterations influence the development of cognitive impairment in patients with obstructive sleep apnea (OSA). However, the literature has limited evidence regarding the neuropathophysiological mechanisms behind these impairments. This research aimed to investigate brain morphologic and functional connectivity (FC) abnormalities related to neurocognitive function in OSA. MethodsFifty treatment-naïve males, newly diagnosed patients with severe OSA, and 50 well-matched healthy controls (HCs) were enrolled prospectively. All subjects underwent an MRI scan, cognitive psychological and sleep scale assessment. The differences of brain morphological and seed-based FC between the two groups were compared. The correlation analysis and receiver operating characteristic curve were performed for further analysis. ResultsCompared with HCs, the right brainstem, left dorsal-lateral superior frontal gyrus (SFGdor), and superior temporal gyrus (STG) exhibited atrophy in the OSA group. In addition, FC between the left SFGdor and the right postcentral gyrus (PoCG) was increased, which was positively correlated with disease duration (r = 0.312, FDR-corrected P = 0.027). The Jacobian values of the brainstem were negatively correlated with MoCA and recall scores (r = −0.449, FDR-corrected P = 0.0025; r = −0.416, FDR-corrected P = 0.005). Furthermore, the Jacobian values of the left SFGdor demonstrated a relatively high diagnostic performance (sensitivity: 86%, specificity: 56%, AUC: 0.740, 95% CI: 0.643–0.836, P < 0.0001). ConclusionsStructural atrophy in brainstem and frontotemporal lobe and altered FC may be the neurobiological hallmark of brain impairment in OSA. Notably, brainstem atrophy has been associated with cognitive impairment, which may provide new insights into understanding the neuropathophysiological mechanisms of cognitive impairment in OSA patients.

0551 Predicting Daytime Alertness Impairment in Obstructive Sleep Apnea

Abstract Introduction Obstructive sleep apnea (OSA) reduces daytime alertness leading to social and occupational impairment. The Maintenance of Wakefulness Test (MWT), a gold-standard test for daytime alertness, is time-consuming and not routinely available in clinical practice. We examined EEG-based and clinical parameters derived from diagnostic polysomnography (PSG) as predictors of alertness impairment in adults with OSA. Methods Eighty-two participants with untreated OSA on diagnostic PSG (apnea hypopnea index, AHI ≥5/hour), enrolled in a two-center clinical trial were included. The day following PSG, each participant completed four 40-minute MWT and four 10-minute Psychomotor Vigilance Tests (PVT). The outcomes were MWT mean sleep latency (MSL) and PVT lapses (reaction time ≥500 milliseconds, square root transformed). Three multiple linear regression models were used: 1. “standard predictors” (total sleep time, TST, percent REM and slow wave sleep, AHI, time &amp;lt; 90% oxygen saturation, and arousal index), 2. “novel predictors” derived by spectral analysis and averaged across right and left central EEG (normalized EEG power, odds ratio product; ORP parameters, and spindle characteristics), and 3. combined standard and novel predictors. Age, sex, and body mass index (BMI) were included in each model, and backward elimination (step AIC) was used for models 2 and 3. Results Participants were middle-aged (mean ± standard deviation, SD 53.5±8.7 years), with moderate OSA (AHI 33.8±18.2) and daytime sleepiness (Epworth Sleepiness Scale 11.7±3.9), and 86% were men. The adjusted r2 for MSL were: model 1=0.09, model 2=0.16, and model 3=0.27, and PVT lapses were: model 1=0.09, model 2=0.31, and model 3=0.34. For MSL, the significant predictors in model 3 included TST (t-statistic -3.59, p=0.0007), REM% (2.51, p=0.01), ORP-9 (2.95, p=0.004), ORP NREM (-3.15, p=0.002), spindle frequency (-2.95, p=0.004), and normalized EEG power (-2.59, p=0.01). For PVT lapses, model 3 predictors included 2.25-2.5 ORP% (-2.91, p=0.005), normalized EEG power (3.22, p=0.002), spindle power (-4.30, p&amp;lt; 0.0001), spindle frequency (2.83, p=0.006), and sex (men vs. women, -2.56, p=0.01). Conclusion We have identified several novel PSG EEG-based predictors of impaired daytime alertness in OSA that will improve occupational evaluation and prognostication in OSA after future validation. Support (if any) National Institutes of Health, UM1-HL112856, UL1TR001422, and UL1TR002003.

Neuronal glutamate transporters are associated with cognitive impairment in obstructive sleep apnea patients without dementia

Increasing evidence supports a link between obstructive sleep apnea (OSA) and cognition, and the mechanism is complex and still not well understood. We analyzed the relationship between the glutamate transporters and cognitive impairment in OSA. For this study 317 subjects without dementia, including 64 healthy controls (HCs), 140 OSA patients with mild cognitive impairment (MCI) and 113 OSA patients without cognitive impairment were assessed. All participants who completed polysomnography, cognition and white matter hyperintensity (WMH) volume were used. Plasma neuron-derived exosomes (NDEs) excitatory amino acid transporter 2 (EAAT2) and vesicular glutamate transporter 1 (VGLUT1) proteins were measured by ELISA kits. After 1 year of continuous positive airway pressure (CPAP) treatment, we analyzed plasma NDEs EAAT2 level and cognition changes. Plasma NDEs EAAT2 level was significantly higher in OSA patients than in HCs. Higher plasma NDEs EAAT2 level were significantly associated with cognitive impairment than normal cognition in OSA patients. Plasma NDEs EAAT2 level was inversely associated with the total Montreal Cognitive Assessment (MoCA) scores, visuo-executive function, naming, attention, language, abstraction, delayed recall and orientation. One year after CPAP treatment, plasma NDEs EAAT2 level (P = 0.019) was significantly lower, while MoCA scores (P = 0.013) were significantly increased compared with baseline. Upregulation of neuronal glutamate transporters at baseline may reflect a self-compensatory mechanism to prevent further neuronal damage, while plasma NDEs EAAT2 level was decreased after one year of CPAP therapy, which may be due to the loss of astrocytes and neurons.

IL-33/ST2 mediating systemic inflammation and neuroinflammation through NF-kB participated in the neurocognitive impairment in obstructive sleep apnea.

Increasing evidence has noted that neuroinflammation contributes to the pathological processes of cognitive impairment of obstructive sleep apnea (OSA) patients. Interleukin (IL) -33/suppression of tumorigenicity 2 (ST2) signaling pathway plays well-defined roles in the inflammatory progression. The study aims to elucidate whether IL-33/ST2 signaling pathway plays a role in the cognitive dysfunction in patients with OSA via regulating neuroinflammation. We found that compared with control subjects, patients with OSA showed significantly elevated IL-33, ST2 and p65 nuclear factor-kappa B (NF-κB) levels in peripheral blood mononuclear cells (PBMCs) and inflammatory cytokines IL-6, IL-8 in serum, which were positively correlated with disease severity. Meanwhile, OSA patients exhibited a decline in Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores, suggesting mild cognitive impairment. Continuous positive airway pressure (CPAP) treatment for 12weeks significantly decreased the expression of IL-33, ST2, p65NF-κB, IL-6 and IL-8, as well as improved cognitive function of OSA patients. Moreover, the IL-33/ST2 signaling was closely correlated with sleep respiratory parameters and cognitive dysfunction. To further explore the underlying mechanism of IL-33/ST2 signaling pathway, we stimulated human microglial clone 3 (HMC3) cells with lipopolysaccharide (LPS) to mimic neuroinflammatory response in vitro. The results showed that LPS treatment led to an increase in IL-33 and ST2 expression in a dose- dependent manner, along with an increased secretion of IL-6 and IL-8. Functional experiments showed that knockdown of IL-33 ameliorated LPS-induced neuroinflammation via suppressing NF-κB signaling. Overall, current findings suggest that IL-33/ST2 signaling participated in the cognitive impairment of OSA patients by promoting neuroinflammation via activating NF-κB signaling. These results may provide a novel therapeutic target for treating OSA- associated cognitive dysfunction.

Complement protein levels in serum astrocyte-derived exosomes are associated with cognitive impairment in obstructive sleep apnea.

An association between neuroinflammation and cognitive decline has been established. The complement system regulates neuroinflammation. Dysregulation, impairment, or inadvertent activation of complement components contribute to preclinical Alzheimer's disease. The astrocyte-derived exosome (ADE) complement proteins, including C3b and C5b-9, may be predictive biomarkers of mild cognitive impairment conversion to Alzheimer's disease dementia. We hypothesized that complement proteins might be involved in cognitive impairment during obstructive sleep apnea (OSA). The aim of our study was to explore the correlation between the complement system and mild cognitive impairment (MCI) in patients with OSA. All participants with subjective snoring complaints from the Sleep Medicine Center underwent polysomnography. OSA was defined as apnea-hypopnea index ≥ 5 events/h. MCI was defined as the Montreal Cognitive Assessment < 26 and met the criteria: (1) a subjective cognitive impairment; (2) an objective impairment in 1 or more cognitive domains; (3) complex instrumental daily abilities can be slightly impaired but independent daily living abilities are maintained; and (4) no dementia. The ADEs were isolated immunochemically for enzyme-linked immunosorbent assay quantification of complement proteins, including C3b, C5b-9, and CD55. The participants who received continuous positive airway pressure were followed up and their complement protein levels were reassessed after 1 year of treatment. A total of 212 participants (66.98% males; mean age of 56.71 ± 10.10 years) were divided into the OSA+MCI group (n = 90), OSA-MCI group (n = 79), and controls (normal cognitive state without OSA) (n = 43). The ADE levels of C3b and C5b-9 in the OSA+MCI group were higher than those in the OSA-MCI and control groups. The C3b and C5b-9 were independently associated with cognitive impairment in patients with OSA. The relationship between apnea-hypopnea index and Montreal Cognitive Assessment scores was mediated by C3b and C5b-9. We found no linear correlation between the complement proteins and the severity of OSA. The complement proteins were negatively correlated with global cognitive performance and cognitive subdomains. The complement protein levels significantly decreased after continuous positive airway pressure treatment. Complement proteins were implicated in cognitive impairment in patients with OSA and may be promising biomarkers for predicting cognitive impairment in patients with OSA. Registry: Chinese Clinical Trial Registry; Name: Study on early diagnostic markers in patients with dementia and mild cognitive impairment; URL: https://www.chictr.org.cn/; Identifier: ChiCTR1900021544. Li M, Sun C, Xue S, etal. Complement proteins levels in serum astrocyte-derived exosomes are associated with cognitive impairment in obstructive sleep apnea. J Clin Sleep Med. 2023;19(4):727-739.

Elevated complement component 8 gamma levels in astrocyte-derived exosomes are associated with cognitive impairment in obstructive sleep apnea patients without dementia

The complement system plays a crucial role in cognitive impairment in obstructive sleep apnea (OSA). The present study aimed to investigate the connections between complement component 8 gamma (C8G) levels in astrocyte-derived exosomes (ADEs) and cognitive impairment in OSA patients without dementia. This cross-sectional cohort study recruited 274 participants without dementia, including 124 OSA patients with mild cognitive impairment (MCI), 100 OSA patients without MCI, and 50 healthy control subjects. Enrolled participants underwent polysomnography (PSG) evaluation, neuropsychological scale assessment, magnetic resonance imaging scanning, and collection of peripheral blood samples for quantification of complement proteins in ADEs. The findings showed higher C8G concentrations in ADEs from OSA patients with MCI than in the controls and OSA without MCI group. Logistic regression analysis suggested that C8G levels in ADEs were independently associated with MCI in OSA patients. Multivariable linear regression analysis demonstrated that C8G levels in ADEs were significantly correlated with global cognitive scores and all cognitive subdomain scores after adjusting for demographic factors (age, sex, education), vascular risk factors (Body mass index, history of hypertension, diabetes, dyslipidemia), depressive symptoms measures, and apnea-hypopnea index (AHI) values. The levels of C8G were linearly positively related to the white matter hyperintensity (WMH) volumes in Pearson's correlation analysis. Our research confirmed that C8G levels are significantly associated with cognitive impairment in OSA patients, which paves the way for novel therapeutic targets for neurocognitive dysfunction progression in OSA patients in the future.

Involvement of Galectin-3 in neurocognitive impairment in obstructive sleep apnea via regulating inflammation and oxidative stress through NLRP3

ObjectiveAccumulated studies have revealed that oxidative stress and inflammation play important roles in the development of OSA related cognitive dysfunction. Galectin-3, a member of the galectin family, has been reported to be involved in the neuroinflammatory diseases. However, the relationship between Galectin-3 and cognitive impairment in OSA remains ambiguous. Materials and methods47 new diagnosed OSA patients and 18 age-, gender-, education- and body mass index-matched healthy control subjects were enrolled in the present study. All subjects underwent whole-night in-laboratory polysomnography (PSG). Montreal Cognitive Assessment (MoCA) was used to evaluated the cognitive function of OSA patients. Serum Galectin-3, interleukin (IL)-1β and IL-8 were examined by enzyme-linked immunosorbent assay (ELISA). The levels of malonaldehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) were measured to evaluate oxidative stress. Protein level of Galectin-3 and NLRP3 in peripheral blood mononuclear cells (PBMCs) and human microglial clone 3 (HMC3) cells were measured by Western Blot. ResultsSerum Galectin-3 level in severe OSA patients (2.31 ± 0.43 ng/m) was higher than those in mild-moderate OSA patients (1.87 ± 0.32 ng/m, p < 0.001) and those in the healthy controls (1.56 ± 0.22 ng/ml, p < 0.001). Similarly, Galectin-3 level in PBMCs was increased with disease severity (p < 0.01). In addition, OSA patients also showed higher levels of inflammation and oxidative stress (p < 0.01). Patients with OSA scored significantly lower than healthy controls on the MoCA test after controlling for age, gender, education, and BMI. CPAP treatment for 12 weeks effectively reduced the levels of Galectin-3, inflammation and oxidative stress, as well as improved cognitive function of severe OSA patients. Closed correlations were observed between Galectin-3 with sleep respiratory parameters and cognitive dysfunction. In addition, we explored the underlying mechanism of Galectin-3 in neuroinflammation and oxidative stress. We treated HMC3 cells with LPS to mimic neuroinflammatory response in vitro. The results showed that LPS treatment led to a dose-dependent increase in Galectin-3 expression, meanwhile induced inflammation and oxidative stress. Inhibiting Galectin-3 with a specific Galectin-3 inhibitor, TD139, significantly ameliorated LPS-induced neuroinflammation and oxidative stress via suppressing NLRP3. ConclusionCurrent findings suggest that increased Galectin-3 might be involved in the cognitive impairment of OSA patients by promoting neuroinflammation and oxidative stress via regulating NLRP3. These results suggested that Galectin-3 inhibition may exert a protective role against the neurocognitive dysfunction associated with OSA.

Abnormal Spontaneous Brain Activity and Cognitive Impairment in Obstructive Sleep Apnea.

PurposeThis study aimed to explore the alterations in spontaneous brain activity in obstructive sleep apnea (OSA) using percent amplitude of fluctuation (PerAF) and investigate the relationship between abnormal spontaneous brain activity and cognitive impairment in OSA.Patients and MethodsOverall, 52 patients with moderate to severe OSA and 61 healthy controls (HCs) were eventually enrolled in this study. All participants underwent resting-state functional magnetic resonance (rs-fMRI) and T1-weighted imaging. The PerAF was calculated and compared between patients with OSA and HCs, with voxel level P < 0.001 and cluster level P < 0.05 corrected with Gaussian Random Field was be considered statistically different. A partial correlation analysis was used to assess the relationship between altered PerAF and clinical assessments in patients with OSA.ResultsCompared to HCs, patients with OSA had significantly lower PerAF values in the right rectal gyrus and left superior frontal gyrus, but higher PerAF values in the right cerebellum posterior lobe and left middle frontal gyrus. The PerAF values of some specific regions in patients with OSA correlated with sleep efficiency and Montreal Cognitive Assessment scores. Additionally, support vector machine analysis showed that PerAF values in all differential brain regions could differentiate patients with OSA from HCs with good accuracy.ConclusionSpecific brain areas in OSA patients may exhibit aberrant neuronal activity, and these anomalies may be linked to decreased cognitive performance. This discovery offers fresh perspectives on these patients’ neurocognition.

Complement activation mainly mediates the association of heart rate variability and cognitive impairment in adults with obstructive sleep apnea without dementia.

The relationship between autonomic nervous system dysfunction measured by heart rate variability (HRV) and cognitive impairment in obstructive sleep apnea (OSA) patients is complex and still not well understood. We aimed to analyze the role of complement activation, Alzheimer's disease (AD) biomarkers, and white matter hyperintensity (WMH) in modulating the association of HRV with cognitive performance. There were 199 subjects without dementia, including 42 healthy controls, 80 OSA patients with mild cognitive impairment (MCI), and 77 OSA patients without cognitive impairment. All participants who completed polysomnography, cognition, WMH volume, and 5-min HRV analysis were recorded during wakefulness and sleep periods. Neuron-derived exosome and astrocyte-derived exosome proteins were measured by ELISA kits. The OSA with MCI group were associated with a lower mean of standard deviations of R-R intervals for 5-min intervals (SDANN index) during wakefulness, standard deviation of the R-R interval (SDNN) during sleep stage and percentage of adjacent R-R intervals differing by more than 50 ms (PNN50) in each stage compared with OSA without MCI. The influence of HRV on cognition was partially mediated by complement activation (C5b-9 mediated a maximum of 51.21%), AD biomarkers, and WMH. Lower SDANN index and PNN50 during wakefulness and SDNN and PNN50 during sleep periods were found in OSA patients with MCI, suggesting potential vulnerability to autonomic and parasympathetic dysfunction. Complement activation, AD biomarkers, and WMH might partially mediate and interact with the influence of HRV on cognitive impairment in OSA patients. ChiCTR1900021544.

Serum sTREM2: A Potential Biomarker for Mild Cognitive Impairment in Patients With Obstructive Sleep Apnea.

ObjectiveCognitive impairment is a common comorbidity in patients with obstructive sleep apnea (OSA) that leads to poor quality of life and a heavier medical burden. However, the assessment and longitudinal tracking of cognitive impairment in OSA is challenging. This study aimed to examine the alternation and related factors of serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in patients with OSA, and to explore whether serum sTREM2 could be a biomarker for mild cognitive impairment in OSA patients.MethodsA total of 94 OSA patients and 13 snoring subjects were enrolled in this cross-sectional study. Demographic information, questionnaires, and polysomnography results were collected. Serum sTREM2 levels were quantified using an enzyme-linked immunosorbent assay. Multivariate linear regression was used to analyze the factors influencing sTREM2, and the receiver operating characteristic curve was used to assess the predictive value of serum sTREM2 for mild cognitive impairment in patients with OSA.ResultsPatients with OSA had higher serum sTREM2 levels than the controls. Multivariate linear regression analysis showed that serum sTREM2 levels in patients with OSA were associated with the Montreal Cognitive Assessment score and oxygen depletion index levels. Additionally, serum sTREM2 levels were higher in OSA patients with mild cognitive impairment (MCI) than in those without. The receiver operating characteristic curve showed that at a cutoff value of >18,437 pg/ml, the sensitivity of serum sTREM2 to predict MCI in OSA was 64.62%, the specificity was 68.97%, and the area under the curve was 0.70 (95% CI: 0.58–0.81).ConclusionSerum sTREM2 levels were elevated in patients with OSA, particularly in those with MCI. It therefore has the potential to be a biomarker for MCI in OSA patients.

Fast assessment of left ventricular systolic function in obstructive sleep apnea patients with automated function imaging: Comparison with mitral annular plane systolic excursion.

Early detection of left ventricular (LV) subclinical dysfunction is clinically relevant before developing irreversible impairment in obstructive sleep apnea (OSA) patients. Mitral annulus plane systolic excursion (MAPSE) is a fast tool for OSA due to high prevalent obesity; another quick but more comprehensive tool is LV global longitudinal stain (GLS) based on automated function imaging (AFI). We therefore aimed to compare the feasibility and reproducibility of AFI to MAPSE in OSA patients, as a good model in whom obesity is common. A comprehensive echocardiographic examination was done in 186 consecutive patients having polysomnography for suspected OSA. MAPSE was measured by using M-mode to calculate excursion of mitral annulus. GLS was derived by offline analysis of three long-axis views that semi-automatically detects LV endocardial boundary, which is adjusted manually as necessary with AFI measurement. Variability of AFI and MAPSE were compared among the different subgroups. Despite a relatively high obesity rate (42.9%), the feasibility of AFI was 94% (175/186) and that of 100% in MAPSE. AFI showed excellent correlation (r=.882) superior to MAPSE (r=.819) between the Expert and Beginner. Intra- and inter- observer variability of AFI and MAPSE in Bland-Altman analysis were 5.5% and 6.5%; 6.2% and 8.8%, respectively. In repeated measurements, AFI showed higher intra-class correlation (ICC=.95) than MAPSE (ICC=.87) (p<0.05). Furthermore, analysis showed that AFI was feasible even in more obese patients (BMI≥28kg/m2 ). Even in obese patients with OSA, AFI-GLS is feasible and more reliable for less expert operators than MAPSE in detecting LV longitudinal dysfunction.

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.

Contribution of hypercapnia to cognitive impairment in severe sleep-disordered breathing.

Although cognitive impairment in obstructive sleep apnea (OSA) is primarily attributed to intermittent hypoxemia and sleep fragmentation, hypercapnia may also play a role in patients whose OSA is complicated by hypoventilation. This study investigated the impact of hypercapnia on cognitive function in severe sleep-disordered breathing (OSA accompanied by hypoventilation). Patients with severe OSA (apnea-hypopnea index >30 events/h; n = 246) underwent evaluation for accompanying hypoventilation with polysomnography that included continuous transcutaneous carbon dioxide (TcCO2) monitoring and awake arterial blood gas analysis. Patients were categorized as having no hypoventilation (n = 84), isolated sleep hypoventilation (n = 40), or awake hypoventilation (n = 122). Global cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA), memory with the Rey Auditory Verbal Learning Test (RAVLT), and processing speed with the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV), Digit Symbol Coding subtest (DSC). Apnea-hypopnea index was similar across groups (P = .15), but the sleep and awake hypoventilation groups had greater nocturnal hypoxemia compared with the no-hypoventilation group (P < .01). Within all groups, mean MoCA scores were < 26, which is the validated threshold to indicate mild cognitive impairment; RAVLT scores were lower than age-matched norms only in the awake-hypoventilation group (P ≤ .01); and DSC scores were lower than age-matched norms within all groups (P < .01). In multivariable regression analyses, higher arterial partial pressure of carbon dioxide (PaCO2) and TcCO2 during wakefulness were associated with lower MoCA and DSC scores (P ≤ .03), independent of confounders including overlap syndrome (OSA + chronic obstructive pulmonary disease). Awake hypoventilation is associated with greater deficits in cognitive function in patients with severe sleep-disordered breathing. Beaudin AE, Raneri JK, Ayas NT, Skomro RP, Smith EE, Hanly PJ; on behalf of Canadian Sleep and Circadian Network. Contribution of hypercapnia to cognitive impairment in severe sleep-disordered breathing. J Clin Sleep Med. 2022;18(1):245-254.

Association between nocturnal activity of the sympathetic nervous system and cognitive dysfunction in obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is associated with repetitive breathing obstructions during sleep. These episodes of hypoxia and associated arousals from sleep induce physiological stress and nocturnal over-activation of the sympathetic nervous system (SNS). One consequence of OSA is impairment in a range of cognitive domains. Previous research into cognitive impairment in OSA have focussed on intermittent hypoxia and disrupted sleep, but not nocturnal over-activation of the SNS. Therefore, we investigated whether nocturnal over-activity of the SNS was associated with cognitive impairments in OSA. The extent of nocturnal SNS activation was estimated from heart rate variability (HRV), pulse wave amplitude (PWA) and stress response biomarkers (cortisol and glucose levels). OSA severity was significantly associated with PWA indices and the HRV low frequency/ high frequency ratio (p < 0.05). Morning blood glucose levels were significantly associated with the duration of a blood oxygen saturation (SaO2) < 90% (p < 0.01). PWA and HRV were significantly associated with the time taken to perform a task involving visuospatial functioning (p < 0.05), but not with impairments in sustained attention, reaction time or autobiographical memory. These results suggest that the visuospatial dysfunction observed in people with OSA is associated with increased nocturnal activity of the SNS.

Differential associations of hypoxia, sleep fragmentation, and depressive symptoms with cognitive dysfunction in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by recurrent episodes of partial or complete cessation of breathing during sleep and increased effort to breathe. This study examined patients who underwent overnight polysomnographic studies in a major sleep laboratory in Saudi Arabia. The study aimed to determine the extent to which intermittent hypoxia, sleep disruption, and depressive symptoms are independently associated with cognitive impairments in OSA. In the sample of 90 participants, 14 had no OSA, 30 mild OSA, 23 moderate OSA, and 23 severe OSA. The findings revealed that hypoxia and sleep fragmentation are independently associated with impairments of sustained attention and reaction time (RT). Sleep fragmentation, but not hypoxia, was independently associated with impairments in visuospatial deficits. Depressive symptoms were independently associated with impairments in the domains of sustained attention, RT, visuospatial ability, and semantic and episodic autobiographical memories. Since the depressive symptoms are independent of hypoxia and sleep fragmentation, effective reversal of cognitive impairment in OSA may require treatment interventions that target each of these factors.

Can electrophysiological tests be used as screening tools in detection of cognitive impairment in obstructive sleep apnea hypopnea syndrome?

BackgroundOne of the most prevalent sleep disorders is obstructive sleep apnea (OSA). Patients with OSA have increased risk of car and work place accidents which may be attributed to cognitive impairment due to poor sleep quality. Thus, there is an increasing need to implement simple, reliable and rapid screening for cognitive impairment in OSA patients.ObjectivesTo assess auditory event-related potentials (ERPs) and quantitative electroencephalography (QEEG) as screening tools for detection of cognitive impairment in OSA patients taking circadian effects into consideration.Subjects and methodsTwenty OSA patients as well as 20 gender- and age-matched volunteers were subjected to trail making test (TMT), auditory ERPs and QEEG before and after at least 6 h polysomnographic recording. Correlating electrophysiological tools with TMT and clinical parameters was done as wellResultsStatistically significant changes in P300 latency and reaction time, in addition to occipital alpha power were noted in cases; however, TMT failed to detect such changes. Electrophysiological results were not constantly correlated to clinical parameters.ConclusionAuditory ERPs and QEEG before and after polysomnography can be of benefit as cognitive screening test for suspected cognitive impairment in OSA patients.

Non Invasive Assessment Of Pulmonary Artery Stiffness And Right Ventricular Function In Patients With Obstructive Sleep Apnea

Aim: to evaluate pulmonary artery stiffness and right ventricular function to predict early RV impairment in obstructive sleep apnea (OSA). We also aimed to assess the use of anticoagulants in patients with elevated pulmonary artery pressure and OSA.Patients and methods: this study was performed on one hundred cases with OSA who did polysomnography study detecting the complete cessation of respiration and hypoventilation episodes, then estimation of serum fibrinogen, platelets, hepatic and renal functions and blood sugar, conventional echocardiography to measure right ventricular ejection fraction (RVEF), tricuspid annular plane systolic excurtion (TAPSE), myocardial performance index (MPI), fractional area change (FAC), linear diameters of right ventricular inflow tract (RVOT), right ventricular (RV) free wall thickness, Doppler assessment of pulmonary artery stiffness (PAS) and speckle tracking echocardiography (STE) .Results: There was a highly noticed difference among the study groups regarding Fibrinogen, platelet count, RVEF, TAPSE, GLS and PAS. There was a positive relation between fibrinogen and apnea-hypopna index (AHI) (r= 0.686, p< 0.001), a positive relation between PAS and AHI (r= 0.515, p< 0.001), a negative relation between RVEF and AHI (r= -0.639, p< 0.001) and a negative relation between GLS and AHI (r=-0.663, p< 0.001). We found that GLS was important with PAS for prediction of RV failure.Conclusion: OSA patients may have a hidden RV systolic impairment detected by STE. PAS may contribute to the development of RV impairment. Elevated fibrinogen is important risk factor for cardiovascular pathology and may direct attention for starting anticoagulation in OSA patients.