Regional variability in intracerebral properties of NREM to REM sleep transitions in humans.

Transitions between wake and sleep states show a progressive pattern underpinned by local sleep regulation. In contrast, little evidence is available on non-rapid eye movement (NREM) to rapid eye movement (REM) sleep boundaries, considered as mainly reflecting subcortical regulation. Using polysomnography (PSG) combined with stereoelectroencephalography (SEEG) in humans undergoing epilepsy presurgical evaluation, we explored the dynamics of NREM-to-REM transitions. PSG was used to visually score transitions and identify REM sleep features. SEEG-based local transitions were determined automatically with a machine learning algorithm using features validated for automatic intra-cranial sleep scoring (10.5281/zenodo.7410501). We analyzed 2988 channel-transitions from 29 patients. The average transition time from all intracerebral channels to the first visually marked REM sleep epoch was 8 s ± 1 min 58 s, with a great heterogeneity between brain areas. Transitions were observed first in the lateral occipital cortex, preceding scalp transition by 1 min 57 s ± 2 min 14 s (d = -0.83), and close to the first sawtooth wave marker. Regions with late transitions were the inferior frontal and orbital gyri (1 min 1 s ± 2 min 1 s, d = 0.43, and 1 min 1 s ± 2 min 5 s, d = 0.43, after scalp transition). Intracranial transitions were earlier than scalp transitions as the night advanced (last sleep cycle, d = -0.81). We show a reproducible gradual pattern of REM sleep initiation, suggesting the involvement of cortical mechanisms of regulation. This provides clues for understanding oneiric experiences occurring at the NREM/REM boundary.

Divergent Associations of Slow-Wave Sleep versus Rapid Eye Movement Sleep with Plasma Amyloid-Beta.

OBJECTIVE: Recent evidence shows that during slow-wave sleep (SWS), the brain is cleared from potentially toxic metabolites, such as the amyloid-beta protein. Poor sleep or elevated cortisol levels can worsen amyloid-beta clearance, potentially leading to the formation of amyloid plaques, a neuropathological hallmark of Alzheimer disease. Here, we explored how nocturnal neural and endocrine activity affects amyloid-beta fluctuations in the peripheral blood. METHODS: We acquired simultaneous polysomnography and all-night blood sampling in 60 healthy volunteers aged 20-68 years. Nocturnal plasma concentrations of amyloid-beta-40, amyloid-beta-42, cortisol, and growth hormone were assessed every 20 minutes. Amyloid-beta fluctuations were modeled with sleep stages, (non)oscillatory power, and hormones as predictors while controlling for age and participant-specific random effects. RESULTS: Amyloid-beta-40 and amyloid-beta-42 levels correlated positively with growth hormone concentrations, SWS proportion, and slow-wave (0.3-4Hz) oscillatory and high-band (30-48Hz) nonoscillatory power, but negatively with cortisol concentrations and rapid eye movement sleep (REM) proportion measured 40-100 minutes previously (all t values > |3|, p values < 0.003). Older participants showed higher amyloid-beta-40 levels. INTERPRETATION: Slow-wave oscillations are associated with higher plasma amyloid-beta levels, whereas REM sleep is related to decreased amyloid-beta plasma levels, possibly representing changes in central amyloid-beta production or clearance. Strong associations between cortisol, growth hormone, and amyloid-beta presumably reflect the sleep-regulating role of the corresponding releasing hormones. A positive association between age and amyloid-beta-40 may indicate that peripheral clearance becomes less efficient with age. ANN NEUROL 2024;96:46-60.

Somnotate: A probabilistic sleep stage classifier for studying vigilance state transitions.

Electrophysiological recordings from freely behaving animals are a widespread and powerful mode of investigation in sleep research. These recordings generate large amounts of data that require sleep stage annotation (polysomnography), in which the data is parcellated according to three vigilance states: awake, rapid eye movement (REM) sleep, and non-REM (NREM) sleep. Manual and current computational annotation methods ignore intermediate states because the classification features become ambiguous, even though intermediate states contain important information regarding vigilance state dynamics. To address this problem, we have developed "Somnotate"-a probabilistic classifier based on a combination of linear discriminant analysis (LDA) with a hidden Markov model (HMM). First we demonstrate that Somnotate sets new standards in polysomnography, exhibiting annotation accuracies that exceed human experts on mouse electrophysiological data, remarkable robustness to errors in the training data, compatibility with different recording configurations, and an ability to maintain high accuracy during experimental interventions. However, the key feature of Somnotate is that it quantifies and reports the certainty of its annotations. We leverage this feature to reveal that many intermediate vigilance states cluster around state transitions, whereas others correspond to failed attempts to transition. This enables us to show for the first time that the success rates of different types of transition are differentially affected by experimental manipulations and can explain previously observed sleep patterns. Somnotate is open-source and has the potential to both facilitate the study of sleep stage transitions and offer new insights into the mechanisms underlying sleep-wake dynamics.

Neural signatures of sleep in zebrafish.

Slow-wave sleep and rapid eye movement (or paradoxical) sleep have been found in mammals, birds and lizards, but it is unclear whether these neuronal signatures are found in non-amniotic vertebrates. Here we develop non-invasive fluorescence-based polysomnography for zebrafish, and show-using unbiased, brain-wide activity recording coupled with assessment of eye movement, muscle dynamics and heart rate-that there are at least two major sleep signatures in zebrafish. These signatures, which we term slow bursting sleep and propagating wave sleep, share commonalities with those of slow-wave sleep and paradoxical or rapid eye movement sleep, respectively. Further, we find that melanin-concentrating hormone signalling (which is involved in mammalian sleep) also regulates propagating wave sleep signatures and the overall amount of sleep in zebrafish, probably via activation of ependymal cells. These observations suggest that common neural signatures of sleep may have emerged in the vertebrate brain over 450 million years ago.

Temporal relations between peripheral and central arousals in good and poor sleepers.

Good sleepers and patients with insomnia symptoms (poor sleepers) were tracked with two measures of arousal; conventional polysomnography (PSG) for electroencephalogram (EEG) assessed cortical arousals, and a peripheral arterial tonometry device was used for the detection of peripheral nervous system (PNS) arousals associated with vasoconstrictions. The relationship between central (cortical) and peripheral (autonomic) arousals was examined by evaluating their close temporal dynamics. Cortical arousals almost invariably were preceded and followed by peripheral activations, while large peripheral autonomic arousals were followed by cortical arousals only half of the time. The temporal contiguity of these two types of arousals was altered in poor sleepers, and poor sleepers displayed a higher number of cortical and peripheral arousals compared with good sleepers. Given the difference in the number of peripheral autonomic arousals between good and poor sleepers, an evaluation of such arousals could become a means of physiologically distinguishing poor sleepers.

Tandem Mass Tag-Labeled Quantitative Proteome Analyses Identify C1R and A2M as Novel Serum Biomarkers in Pregnant Women with Obstructive Sleep Apnea.

The aim of this study was to identify serum diagnostic biomarkers associated with the severity of obstructive sleep apnea (OSA) during pregnancy. Differentially expressed proteins (DEPs) were identified in the control (C), mild (O), and moderate (MO) OSA groups (n = 3 in each group). Bioinformatics analysis was conducted to identify the underlying functions, pathways, and networks of the proteins. Receiver operating characteristic curves were used to assess the diagnostic value of the identified DEPs. The enzyme-linked immunoassay was performed to detect serum levels of the complement C1r subcomponent (C1R) and alpha-2-macroglobulin (A2M) in 79 pregnant women with OSA (mild OSA [n = 32]; moderate OSA [n = 29], and severe OSA [n = 18]) and 65 healthy pregnant women without OSA. Pearson's correlation analysis was conducted to analyze the correlation between C1R and A2M levels and OSA clinicopathological factors. In total, 141 DEPs, 29 DEPs, and 103 DEPs were identified in the three groups (i.e., the mild OSA vs control group, the moderate OSA vs mild apnea group, and the moderate OSA vs control group, respectively). C1R and A2M were identified as continuously up-regulated proteins, and the levels of C1R and A2M were associated with OSA severity. C1R and A2M were found to be correlated with body mass index, systolic blood pressure, apnea-hypopnea index, oxygen desaturation index, time with saturation below 90%, and lowest SaO2. Adverse maternal and neonatal outcomes were observed in pregnant women with OSA. C1R and A2M have been identified as diagnostic biomarkers and are associated with the severity of OSA during pregnancy.

Comparative analysis of sleep parameters and structures derived from wearable flexible electrode sleep patches and polysomnography in young adults.

Polysomnography (PSG) is the gold standard for clinical sleep monitoring, but its cost, discomfort, and limited suitability for continuous use present challenges. The flexible electrode sleep patch (FESP) emerges as an economically viable and patient-friendly solution, offering lightweight, simple operation, and self-applicable. Nevertheless, its utilization in young individuals remains uncertain. The objective of this study was to compare sleep data obtained by FESP and PSG in healthy young individuals and analyze agreement for sleep parameters and structure classification. Overnight monitoring with FESP and PSG recordings in 48 participants (mean age: 23 yr) was done. Correlation analysis, Bland-Altman plots, and Cohen's kappa coefficient assessed consistency. Sensitivity, specificity, and predictive values compared classification against PSG. FESP showed strong correlation and consistency with PSG for sleep monitoring. Bland-Altman plots indicated small errors and high consistency. Kappa values (0.70-0.84) suggested substantial agreement for sleep stage classification. Pearson correlation coefficient values for sleep stages (0.75-0.88) and sleep parameters (0.80-0.96) confirm that FESP has a strong application. Intraclass correlation coefficient yielded values between 0.65 and 0.97. In addition, FESP demonstrated an impressive accuracy range of 84.12-93.47% for sleep stage classification. The FESP also features a wearable self-test program with an error rate of no more than 8% for both deep sleep and wake. In young adults, FESP demonstrated reliable monitoring capabilities comparable to PSG. With its low cost and user-friendly design, FESP is a potential alternative for portable sleep assessment in clinical and research applications. Further studies involving larger populations are needed to validate its diagnostic potential.NEW & NOTEWORTHY By comparison with PSG, this study confirmed the reliability of an efficient, objective, low-cost, and noninvasive portable automatic sleep-monitoring device FESP, which provides effective information for long-term family sleep disorder diagnosis and sleep quality monitoring.

Reduced overnight memory consolidation and associated alterations in sleep spindles and slow oscillations in early Alzheimer's disease.

Spatial navigation critically underlies hippocampal-entorhinal circuit function that is early affected in Alzheimer's disease (AD). There is growing evidence that AD pathophysiology dynamically interacts with the sleep/wake cycle impairing hippocampal memory. To elucidate sleep-dependent consolidation in a cohort of symptomatic AD patients (n = 12, 71.25 ± 2.16 years), we tested hippocampal place learning by means of a virtual reality task and verbal memory by a word-pair association task before and after a night of sleep. Our results show an impaired overnight memory retention in AD compared with controls in the verbal task, together with a significant reduction of sleep spindle activity (i.e., lower amplitude of fast sleep spindles, p = 0.016) and increased duration of the slow oscillation (SO; p = 0.019). Higher spindle density, faster down-to-upstate transitions within SOs, and the time delay between SOs and nested spindles predicted better memory performance in healthy controls but not in AD patients. Our results show that mnemonic processing and memory consolidation in AD is slightly impaired as reflected by dysfunctional oscillatory dynamics and spindle-SO coupling during NonREM sleep. In this translational study based on experimental paradigms in animals and extending previous work in healthy aging and preclinical disease stages, our results in symptomatic AD further deepen the understanding of the memory decline within a bidirectional relationship of sleep and AD pathology.

Definition of diaphragmatic sleep disordered breathing and clinical meaning in Duchenne muscular dystrophy.

BACKGROUND: Diaphragmatic sleep disordered breathing (dSDB) has been recently identified as sleep dysfunction secondary to diaphragmatic weakness in Duchenne muscular dystrophy (DMD). However, scoring criteria for the identification of dSDB are missing.This study aimed to define and validate dSDB scoring criteria and to evaluate whether dSDB severity correlates with respiratory progression in DMD. METHODS: Scoring criteria for diaphragmatic apnoea (dA) and hypopnoeas (dH) have been defined by the authors considering the pattern observed on cardiorespiratory polygraphy (CR) and the dSDB pathophysiology.10 sleep professionals (physiologists, consultants) blinded to each other were involved in a two-round Delphi survey to rate each item of the proposed dSDB criteria (Likert scale 1-5) and to recognise dSDB among other SDB. The scorers' accuracy was tested against the authors' panel.Finally, CR previously conducted in DMD in clinical setting were rescored and diaphragmatic Apnoea-Hypopnoea Index (dAHI) was derived. Pulmonary function (forced vital capacity per cent of predicted, FVC%pred), overnight oxygen saturation (SpO2) and transcutaneous carbon dioxide (tcCO2) were correlated with dAHI. RESULTS: After the second round of Delphi, raters deemed each item of dA and dH criteria as relevant as 4 or 5. The agreement with the panel in recognising dSDB was 81%, kappa 0.71, sensitivity 77% and specificity 85%.32 CRs from DMD patients were reviewed. dSDB was previously scored as obstructive. The dAHI negatively correlated with FVC%pred (r=-0.4; p<0.05). The total number of dA correlated with mean overnight tcCO2 (r 0.4; p<0.05). CONCLUSIONS: dSDB is a newly defined sleep disorder that correlates with DMD progression. A prospective study to evaluate dSDB as a respiratory measure for DMD in clinical and research settings is planned.

A novel TASK channel antagonist nasal spray reduces sleep apnea severity in physiological responders: a randomized, blinded, trial.

Preclinical and human physiological studies indicate that topical, selective TASK 1/3 K+ channel antagonism increases upper airway dilator muscle activity and reduces pharyngeal collapsibility during anesthesia and nasal breathing during sleep. The primary aim of this study was to determine the effects of BAY2586116 nasal spray on obstructive sleep apnea (OSA) severity and whether individual responses vary according to differences in physiological responses and route of breathing. Ten people (5 females) with OSA [apnea-hypopnea index (AHI) = 47 ± 26 events/h (means ± SD)] who completed previous sleep physiology studies with BAY2586116 were invited to return for three polysomnography studies to quantify OSA severity. In random order, participants received either placebo nasal spray (saline), BAY2586116 nasal spray (160 µg), or BAY2586116 nasal spray (160 µg) restricted to nasal breathing (chinstrap or mouth tape). Physiological responders were defined a priori as those who had improved upper airway collapsibility (critical closing pressure ≥2 cmH2O) with BAY2586116 nasal spray (NCT04236440). There was no systematic change in apnea-hypopnea index (AHI3) from placebo versus BAY2586116 with either unrestricted or nasal-only breathing versus placebo (47 ± 26 vs. 43 ± 27 vs. 53 ± 33 events/h, P = 0.15). However, BAY2586116 (unrestricted breathing) reduced OSA severity in physiological responders compared with placebo (e.g., AHI3 = 28 ± 11 vs. 36 ± 12 events/h, P = 0.03 and ODI3 = 18 ± 10 vs. 28 ± 12 events/h, P = 0.02). Morning blood pressure was also lower in physiological responders after BAY2586116 versus placebo (e.g., systolic blood pressure = 137 ± 24 vs. 147 ± 21 mmHg, P < 0.01). In conclusion, BAY2586116 reduces OSA severity during sleep in people who demonstrate physiological improvement in upper airway collapsibility. These findings highlight the therapeutic potential of this novel pharmacotherapy target in selected individuals.NEW & NOTEWORTHY Preclinical findings in pigs and humans indicate that blocking potassium channels in the upper airway with topical nasal application increases pharyngeal dilator muscle activity and reduces upper airway collapsibility. In this study, BAY2586116 nasal spray (potassium channel blocker) reduced sleep apnea severity in those who had physiological improvement in upper airway collapsibility. BAY2586116 lowered the next morning's blood pressure. These findings highlight the potential for this novel therapeutic approach to improve sleep apnea in certain people.

Sleep alterations as a function of 88 health indicators.

BACKGROUND: Alterations in sleep have been described in multiple health conditions and as a function of several medication effects. However, evidence generally stems from small univariate studies. Here, we apply a large-sample, data-driven approach to investigate patterns between in sleep macrostructure, quantitative sleep EEG, and health. METHODS: We use data from the MrOS Sleep Study, containing polysomnography and health data from a large sample (N = 3086) of elderly American men to establish associations between sleep macrostructure, the spectral composition of the electroencephalogram, 38 medical disorders, 2 health behaviors, and the use of 48 medications. RESULTS: Of sleep macrostructure variables, increased REM latency and reduced REM duration were the most common findings across health indicators, along with increased sleep latency and reduced sleep efficiency. We found that the majority of health indicators were not associated with objective EEG power spectral density (PSD) alterations. Associations with the rest were highly stereotypical, with two principal components accounting for 85-95% of the PSD-health association. PC1 consists of a decrease of slow and an increase of fast PSD components, mainly in NREM. This pattern was most strongly associated with depression/SSRI medication use and age-related disorders. PC2 consists of changes in mid-frequency activity. Increased mid-frequency activity was associated with benzodiazepine use, while decreases were associated with cardiovascular problems and associated medications, in line with a recently proposed hypothesis of immune-mediated circadian demodulation in these disorders. Specific increases in sleep spindle frequency activity were associated with taking benzodiazepines and zolpidem. Sensitivity analyses supported the presence of both disorder and medication effects. CONCLUSIONS: Sleep alterations are present in various health conditions.

Endotypic traits of supine position and supine-predominant obstructive sleep apnoea in Asian patients.

BACKGROUND: Over half of all cases of obstructive sleep apnoea (OSA) are classified as supine-related OSA; however, the pathological endotype during supine position is not fully understood. This study aims to investigate the endotypic traits of supine-predominant OSA and explore the variations in endotypic traits between the supine and lateral positions. METHODS: We prospectively recruited 689 adult patients with OSA from a single sleep centre between April 2020 and December 2022. Endotypic traits, namely arousal threshold, collapsibility, loop gain and upper airway muscle compensation, were retrieved from polysomnographic signals. We identified spOSA by a supine to non-supine apnoea-hypopnoea index (AHI) ratio >2. We cross-sectionally compared demographic and endotypic traits between supine-predominant OSA and non-positional OSA and examined the associations between supine-predominant OSA and endotypic traits. Additionally, we compared the changes in endotypic traits between supine and lateral positions in patients with supine-predominant OSA and non-positional OSA. RESULTS: In our study sample, 75.8% of patients were identified as having supine-predominant OSA. Compared to non-positional OSA, supine-predominant OSA was associated with low collapsibility (ß= -3.46 %eupnoea, 95% CI -5.93- -1.00 %eupnoea) and reduced compensation (ß= -6.79 %eupnoea, 95% CI -10.60- -2.99 %eupnoea). When transitioning from the lateral to supine position, patients with supine-predominant OSA had a substantial decrease in compensation compared to those with non-positional OSA (-11.98 versus -6.28 %eupnoea). CONCLUSIONS: Supine-predominant OSA is the prevalent phenotype of OSA in Asian patients. Inadequate upper airway compensation appears to be a crucial underlying pathology in patients with supine-predominant OSA.

Polysomnographic airflow shapes and site of collapse during drug-induced sleep endoscopy.

BACKGROUND: Differences in the pharyngeal site of collapse influence efficacy of non-continuous positive airway pressure therapies for obstructive sleep apnoea (OSA). Notably, complete concentric collapse at the level of the palate (CCCp) during drug-induced sleep endoscopy (DISE) is associated with reduced efficacy of hypoglossal nerve stimulation, but CCCp is currently not recognisable using polysomnography. Here we develop a means to estimate DISE-based site of collapse using overnight polysomnography. METHODS: 182 OSA patients provided DISE and polysomnography data. Six polysomnographic flow shape characteristics (mean during hypopnoeas) were identified as candidate predictors of CCCp (primary outcome variable, n=44/182), including inspiratory skewness and inspiratory scoopiness. Multivariable logistic regression combined the six characteristics to predict clear presence (n=22) versus absence (n=128) of CCCp (partial collapse and concurrent tongue base collapse excluded). Odds ratios for actual CCCp between predicted subgroups were quantified after cross-validation. Secondary analyses examined complete lateral wall, tongue base or epiglottis collapse. External validation was performed on a separate dataset (ntotal=466). RESULTS: CCCp was characterised by greater scoopiness (ß=1.5±0.6 per 2sd, multivariable estimate±se) and skewness (ß=11.4±2.4) compared with non-CCCp. The odds ratio for CCCp in predicted positive versus negative subgroups was 5.0 (95% CI 1.9-13.1). The same characteristics provided significant cross-validated prediction of lateral wall (OR 6.3, 95% CI 2.4-16.5), tongue base (OR 3.2, 95% CI 1.4-7.3) and epiglottis (OR 4.4, 95% CI 1.5-12.4) collapse. CCCp and lateral wall collapse shared similar characteristics (skewed, scoopy), diametrically opposed to tongue base and epiglottis collapse characteristics. External validation confirmed model prediction. CONCLUSIONS: The current study provides a means to recognise patients with likely CCCp or other DISE-based site of collapse categories using routine polysomnography. Since site of collapse influences therapeutic responses, polysomnographic airflow shape analysis could facilitate precision site-specific OSA interventions.

Alpha anteriorization and theta posteriorization during deep sleep.

Brain states (wake, sleep, general anesthesia, etc.) are profoundly associated with the spatiotemporal dynamics of brain oscillations. Previous studies showed that the EEG alpha power shifted from the occipital cortex to the frontal cortex (alpha anteriorization) after being induced into a state of general anesthesia via propofol. The sleep research literature suggests that slow waves and sleep spindles are generated locally and propagated gradually to different brain regions. Since sleep and general anesthesia are conceptualized under the same framework of consciousness, the present study examines whether alpha anteriorization similarly occurs during sleep and how the EEG power in other frequency bands changes during different sleep stages. The results from the analysis of three polysomnography datasets of 234 participants show consistent alpha anteriorization during the sleep stages N2 and N3, beta anteriorization during stage REM, and theta posteriorization during stages N2 and N3. Although it is known that the neural circuits responsible for sleep are not exactly the same for general anesthesia, the findings of alpha anteriorization in this study suggest that, at macro level, the circuits for alpha oscillations are organized in the similar cortical areas. The spatial shifts of EEG power in different frequency bands during sleep may offer meaningful neurophysiological markers for the level of consciousness.

Actigraphy Enables Home Screening of Rapid Eye Movement Behavior Disorder in Parkinson's Disease.

OBJECTIVES: Rapid eye movement sleep behavior disorder (RBD) is a potentially harmful, often overlooked sleep disorder affecting up to 70% of Parkinson's disease patients. Current diagnosis relies on nocturnal video-polysomnography, which is an expensive and cumbersome examination requiring specific clinical expertise. Here, we explored the use of wrist actigraphy to enable automatic RBD diagnoses in home settings. METHODS: A total of 26 Parkinson's disease patients underwent 2-week home wrist actigraphy, followed by two in-laboratory evaluations. Patients were classified as RBD versus non-RBD based on dream enactment history and video-polysomnography. We comprehensively characterized patients' movement patterns during sleep using actigraphic signals. We then trained machine learning classification algorithms to discriminate patients with or without RBD using the most relevant features. Classification performance was quantified with respect to clinical diagnosis, separately for in-laboratory and at-home recordings. Performance was further validated in a control group of non-Parkinson's disease patients with other sleep conditions. RESULTS: To characterize RBD, actigraphic features extracted from both (1) individual movement episodes and (2) global nocturnal activity were critical. RBD patients were more active overall, and showed movements that were shorter, of higher magnitude, and more scattered in time. Using these features, our classification algorithms reached an accuracy of 92.9 ± 8.16% during in-clinic tests. When validated on home recordings in Parkinson's disease patients, accuracy reached 100% over a 2-week window, and was 94.4% in non-Parkinson's disease control patients. Features showed robustness across tests and conditions. INTERPRETATION: These results open new perspectives for faster, cheaper, and more regular screening of sleep disorders, both for routine clinical practice and clinical trials. ANN NEUROL 2023;93:317-329.

Predictors of moderate to severe obstructive sleep apnea in patients with lung cancer.

BACKGROUND AND OBJECTIVES: OSA is a known medical condition that is associated with several comorbidities and affect patients' quality of life. The association between OSA and lung cancer remains debated. Some studies reported increased prevalence of OSA in patients with lung cancer. We aimed to assess predictors of moderate-to-severe OSA in patients with lung cancer. METHODS: We enrolled 153 adult patients who were newly diagnosed with lung cancer. Cardiorespiratory monitoring was performed using home sleep apnea device. We carried out Univariate and multivariate logistic regression analysis on multiple parameters including age, gender, smoking status, neck circumference, waist circumference, BMI, stage and histopathology of lung cancer, presence of superior vena cava obstruction, and performance status to find out the factors that are independently associated with a diagnosis of moderate-to-severe OSA. RESULTS: Our results suggest that poor performance status is the most significant predictor of moderate to severe OSA in patients with lung cancer after controlling for important confounders. CONCLUSION: Performance status is a predictor of moderate to severe OSA in patients with lung cancer in our population of middle eastern ethnicity.

Independent relationship between sleep apnea-specific hypoxic burden and glucolipid metabolism disorder: a cross-sectional study.

OBJECTIVES: Obstructive sleep apnea (OSA) is associated with abnormal glucose and lipid metabolism. However, whether there is an independent association between Sleep Apnea-Specific Hypoxic Burden (SASHB) and glycolipid metabolism disorders in patients with OSA is unknown. METHODS: We enrolled 2,173 participants with suspected OSA from January 2019 to July 2023 in this study. Polysomnographic variables, biochemical indicators, and physical measurements were collected from each participant. Multiple linear regression analyses were used to evaluate independent associations between SASHB, AHI, CT90 and glucose as well as lipid profile. Furthermore, logistic regressions were used to determine the odds ratios (ORs) for abnormal glucose and lipid metabolism across various SASHB, AHI, CT90 quartiles. RESULTS: The SASHB was independently associated with fasting blood glucose (FBG) (ß = 0.058, P = 0.016), fasting insulin (FIN) (ß = 0.073, P < 0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (ß = 0.058, P = 0.011), total cholesterol (TC) (ß = 0.100, P < 0.001), total triglycerides (TG) (ß = 0.063, P = 0.011), low-density lipoprotein cholesterol (LDL-C) (ß = 0.075, P = 0.003), apolipoprotein A-I (apoA-I) (ß = 0.051, P = 0.049), apolipoprotein B (apoB) (ß = 0.136, P < 0.001), apolipoprotein E (apoE) (ß = 0.088, P < 0.001) after adjustments for confounding factors. Furthermore, the ORs for hyperinsulinemia across the higher SASHB quartiles were 1.527, 1.545, and 2.024 respectively, compared with the lowest quartile (P < 0.001 for a linear trend); the ORs for hyper-total cholesterolemia across the higher SASHB quartiles were 1.762, 1.998, and 2.708, compared with the lowest quartile (P < 0.001 for a linear trend) and the ORs for hyper-LDL cholesterolemia across the higher SASHB quartiles were 1.663, 1.695, and 2.316, compared with the lowest quartile (P < 0.001 for a linear trend). Notably, the ORs for hyper-triglyceridemia{1.471, 1.773, 2.099} and abnormal HOMA-IR{1.510, 1.492, 1.937} maintained a consistent trend across the SASHB quartiles. CONCLUSIONS: We found SASHB was independently associated with hyperinsulinemia, abnormal HOMA-IR, hyper-total cholesterolemia, hyper-triglyceridemia and hyper-LDL cholesterolemia in Chinese Han population. Further prospective studies are needed to confirm that SASHB can be used as a predictor of abnormal glycolipid metabolism disorders in patients with OSA. TRIAL REGISTRATION: ChiCTR1900025714 { http://www.chictr.org.cn/ }; Prospectively registered on 6 September 2019; China.

Treating sleep-disordered breathing of idiopathic pulmonary fibrosis patients with CPAP and nocturnal oxygen treatment. A pilot study : Sleep-disordered breathing treatment in IPF.

INTRODUCTION: Sleep-disordered breathing (SDB) is a major comorbidity in idiopathic pulmonary fibrosis (IPF) and is associated with a poor outcome. There is a lack of knowledge regarding the impact of SDB treatment on IPF. We assessed at one year: (1) the effect of CPAP and/or nocturnal oxygen therapy on IPF regarding lung function, blood mediators, and quality of life; (2) adherence to SDB treatment and SDB changes. METHODOLOGY: This is a prospective study of consecutive newly diagnosed IPF patients initiating anti-fibrotic treatment. Lung function, polysomnography, blood tests and quality of life questionnaires were performed at inclusion and after one year. Patients were classified as obstructive sleep apnoea (OSA), central sleep apnoea (CSA), and sleep-sustained hypoxemia (SSH). SDB therapy (CPAP and/or nocturnal oxygen therapy) was initiated if needed. RESULTS: Fifty patients were enrolled (36% had OSA, 22% CSA, and 12% SSH). CPAP was started in 54% of patients and nocturnal oxygen therapy in 16%. At one-year, polysomnography found improved parameters, though 17% of patients had to add nocturnal oxygen therapy or CPAP, while 33% presented SDB onset at this second polysomnography. CPAP compliance at one year was 6.74 h/night (SD 0.74). After one year, matrix metalloproteinase-1 decreased in OSA and CSA (p = 0.029; p = 0.027), C-reactive protein in OSA (p = 0.045), and surfactant protein D in CSA group (p = 0.074). There was no significant change in lung function. CONCLUSIONS: Treatment of SBD with CPAP and NOT can be well tolerated with a high compliance. IPF patients may exhibit SDB progression and require periodic re-assessment. Further studies to evaluate the impact of SDB treatment on lung function and serological mediators are needed.

Charting Disease Trajectories from Isolated REM Sleep Behavior Disorder to Parkinson's Disease.

BACKGROUND: Clinical presentation and progression dynamics are variable in patients with Parkinson's disease (PD). Disease course mapping is an innovative disease modelling technique that summarizes the range of possible disease trajectories and estimates dimensions related to onset, sequence, and speed of progression of disease markers. OBJECTIVE: To propose a disease course map for PD and investigate progression profiles in patients with or without rapid eye movement sleep behavioral disorders (RBD). METHODS: Data of 919 PD patients and 88 isolated RBD patients from three independent longitudinal cohorts were analyzed (follow-up duration = 5.1; 95% confidence interval, 1.1-8.1] years). Disease course map was estimated by using eight clinical markers (motor and non-motor symptoms) and four imaging markers (dopaminergic denervation). RESULTS: PD course map showed that the first changes occurred in the contralateral putamen 13 years before diagnosis, followed by changes in motor symptoms, dysautonomia, sleep-all before diagnosis-and finally cognitive decline at the time of diagnosis. The model showed earlier disease onset, earlier non-motor and later motor symptoms, more rapid progression of cognitive decline in PD patients with RBD than PD patients without RBD. This pattern was even more pronounced in patients with isolated RBD with early changes in sleep, followed by cognition and non-motor symptoms and later changes in motor symptoms. CONCLUSIONS: Our findings are consistent with the presence of distinct patterns of progression between patients with and without RBD. Understanding heterogeneity of PD progression is key to decipher the underlying pathophysiology and select homogeneous subgroups of patients for precision medicine. © 2023 International Parkinson and Movement Disorder Society.

Impact of obstructive sleep apnea syndrome on olfactory and gustatory capacity.

Only a few studies have investigated olfactory function in patients with obstructive sleep apnea syndrome (OSAS) using psychophysical testing, and there is a scarcity of data regarding taste evaluation in the existing literature. The primary objectives of this study were to assess both smell and taste in patients with OSAS and to explore the correlation between the severity of symptoms and sensory perception. A total of 85 OSAS patients and a control group comprising 81 subjects were enrolled. Initial assessments included anamnesis, nasal endoscopy, and the completion of questionnaires (Epworth Sleepiness Scale, Visual Analogue Scale, Questionnaire of Olfactory Disorders, and the importance of olfaction questionnaire). The diagnosis of OSAS was confirmed by polysomnography, while nasal airflow was evaluated using rhinomanometry. Olfaction was assessed using the Sniffin' Sticks test, and the Threshold-Discrimination-Identification (TDI) score was calculated. Taste evaluation was conducted in a subgroup of participants (42 patients, 38 controls) using taste strips. The mean TDI score was 31 ±â€…5.6 for OSAS patients and 35 ±â€…4.6 for controls, indicating a significant difference (P < 0.001). Similarly, the taste score was 7 ±â€…3.0 for OSAS patients and 12.6 ±â€…3.2 for controls (P < 0.001). No correlations were observed between TDI and Apnea Hypopnea Index (AHI) (r = -0.12; P = 0.28), as well as between the taste score and AHI (r = -0.31; P = 0.22). However, a weak but significant correlation between TDI score and Epworth Sleepiness Scale was detected (r = -0.05; P = 0.002). The study revealed a significant decrease in sensory perception among patients with OSAS, though open questions persist about the pathophysiology.