Acoustic stimulation as a promising technique to enhance slow-wave sleep in Alzheimer's disease: results of a pilot study.

STUDY OBJECTIVES: Sleep disturbances are common in people with Alzheimer's disease (AD), and a reduction in slow-wave activity is the most striking underlying change. Acoustic stimulation has emerged as a promising approach to enhance slow-wave activity in healthy adults and people with amnestic mild cognitive impairment. In this phase 1 study we investigated, for the first time, the feasibility of acoustic stimulation in AD and piloted the effect on slow-wave sleep (SWS). METHODS: Eleven adults with mild to moderate AD first wore the DREEM 2 headband for 2 nights to establish a baseline registration. Using machine learning, the DREEM 2 headband automatically scores sleep stages in real time. Subsequently, the participants wore the headband for 14 consecutive "stimulation nights" at home. During these nights, the device applied phase-locked acoustic stimulation of 40-dB pink noise delivered over 2 bone-conductance transducers targeted to the up-phase of the delta wave or SHAM, if it detected SWS in sufficiently high-quality data. RESULTS: Results of the DREEM 2 headband algorithm show a significant average increase in SWS (minutes) [t(3.17) = 33.57, P = .019] between the beginning and end of the intervention, almost twice as much time was spent in SWS. Consensus scoring of electroencephalography data confirmed this trend of more time spent in SWS [t(2.4) = 26.07, P = .053]. CONCLUSIONS: Our phase 1 study provided the first evidence that targeted acoustic stimuli is feasible and could increase SWS in AD significantly. Future studies should further test and optimize the effect of stimulation on SWS in AD in a large randomized controlled trial. CITATION: Van den Bulcke L, Peeters A-M, Heremans E, et al. Acoustic stimulation as a promising technique to enhance slow-wave sleep in Alzheimer's disease: results of a pilot study. J Clin Sleep Med. 2023;19(12):2107-2112.

In search of a cut-off apnea-hypopnea index in type 3 home portable monitors to diagnose and treat obstructive sleep apnea: a mathematical simulation.

The American Academy of Sleep Medicine (AASM) uses similar apnea-hypopnea index (AHI) cut-off values to diagnose and define severity of sleep apnea independent of the technique used: in-hospital polysomnography (PSG) or type 3 portable monitoring (PM). Taking into account that PM theoretically might underestimate the AHI, we explored whether a lower cut-off would be more appropriate. We performed mathematical re-calculations on the diagnostic PSG-AHI (scored using AASM 1999 rules) of 865 consecutive patients with an AHI of ≥20 events/h who started continuous positive airway pressure (CPAP). For a PSG-AHI of ≥15 events/h re-scored using AASM 2012 rules (PSG-AHIAASM2012 ), a PM-respiratory event index (REI)AASM2012 cut-off point of ≥15 events/h resulted in a post-test probability of 100% of having the disease, but with negative tests in 57.1%. A PM-REIAASM2012 cut-off of 8 events/h, still resulted in a positive post-test probability of 100% but with negative tests in only 34.3%. Combination of the cut-off values with clinical estimation of being 'at high risk' based on Epworth Sleepiness Scale (ESS) and Berlin Questionnaire scores only resulted in a small reduction in the percentage of negative tests (respectively 52.7% and 32.7%). After 6 months, CPAP adherence was not lower using the PM-REIAASM 2012 cut-off ≥8 events/h in comparison to ≥15 events/h (median 5.7 vs. 5.8 h/night, p = 0.368) and the reduction in ESS was similar too (median -4 and -5 points, p = 0.083). Consequently, using a lower PM-REIAASM2012 cut-off could result in cost savings because of less negative studies and lesser need for a confirmatory PSG or a performance of a CPAP trial.

From unsupervised to semi-supervised adversarial domain adaptation in electroencephalography-based sleep staging.

Objective.The recent breakthrough of wearable sleep monitoring devices has resulted in large amounts of sleep data. However, as limited labels are available, interpreting these data requires automated sleep stage classification methods with a small need for labeled training data. Transfer learning and domain adaptation offer possible solutions by enabling models to learn on a source dataset and adapt to a target dataset.Approach.In this paper, we investigate adversarial domain adaptation applied to real use cases with wearable sleep datasets acquired from diseased patient populations. Different practical aspects of the adversarial domain adaptation framework are examined, including the added value of (pseudo-)labels from the target dataset and the influence of domain mismatch between the source and target data. The method is also implemented for personalization to specific patients.Main results.The results show that adversarial domain adaptation is effective in the application of sleep staging on wearable data. When compared to a model applied on a target dataset without any adaptation, the domain adaptation method in its simplest form achieves relative gains of 7%-27% in accuracy. The performance in the target domain is further boosted by adding pseudo-labels and real target domain labels when available, and by choosing an appropriate source dataset. Furthermore, unsupervised adversarial domain adaptation can also personalize a model, improving the performance by 1%-2% compared to a non-personalized model.Significance.In conclusion, adversarial domain adaptation provides a flexible framework for semi-supervised and unsupervised transfer learning. This is particularly useful in sleep staging and other wearable electroencephalography applications. (Clinical trial registration number: S64190.).

Capacitively-Coupled ECG and Respiration for Sleep-Wake Prediction and Risk Detection in Sleep Apnea Patients.

Obstructive sleep apnea (OSA) patients would strongly benefit from comfortable home diagnosis, during which detection of wakefulness is essential. Therefore, capacitively-coupled electrocardiogram (ccECG) and bioimpedance (ccBioZ) sensors were used to record the sleep of suspected OSA patients, in parallel with polysomnography (PSG). The three objectives were quality assessment of the unobtrusive signals during sleep, prediction of sleep-wake using ccECG and ccBioZ, and detection of high-risk OSA patients. First, signal quality indicators (SQIs) determined the data coverage of ccECG and ccBioZ. Then, a multimodal convolutional neural network (CNN) for sleep-wake prediction was tested on these preprocessed ccECG and ccBioZ data. Finally, two indices derived from this prediction detected patients at risk. The data included 187 PSG recordings of suspected OSA patients, 36 (dataset "Test") of which were recorded simultaneously with PSG, ccECG, and ccBioZ. As a result, two improvements were made compared to prior studies. First, the ccBioZ signal coverage increased significantly due to adaptation of the acquisition system. Secondly, the utility of the sleep-wake classifier increased as it became a unimodal network only requiring respiratory input. This was achieved by using data augmentation during training. Sleep-wake prediction on "Test" using PSG respiration resulted in a Cohen's kappa (κ) of 0.39 and using ccBioZ in κ = 0.23. The OSA risk model identified severe OSA patients with a κ of 0.61 for PSG respiration and κ of 0.39 using ccBioZ (accuracy of 80.6% and 69.4%, respectively). This study is one of the first to perform sleep-wake staging on capacitively-coupled respiratory signals in suspected OSA patients and to detect high risk OSA patients based on ccBioZ. The technology and the proposed framework could be applied in multi-night follow-up of OSA patients.

Sleep Diagnostics for Home Monitoring of Sleep Apnea Patients.

Objectives: Sleep time information is essential for monitoring of obstructive sleep apnea (OSA), as the severity assessment depends on the number of breathing disturbances per hour of sleep. However, clinical procedures for sleep monitoring rely on numerous uncomfortable sensors, which could affect sleeping patterns. Therefore, an automated method to identify sleep intervals from unobtrusive data is required. However, most unobtrusive sensors suffer from data loss and sensitivity to movement artifacts. Thus, current sleep detection methods are inadequate, as these require long intervals of good quality. Moreover, sleep monitoring of OSA patients is often less reliable due to heart rate disturbances, movement and sleep fragmentation. The primary aim was to develop a sleep-wake classifier for sleep time estimation of suspected OSA patients, based on single short-term segments of their cardiac and respiratory signals. The secondary aim was to define metrics to detect OSA patients directly from their predicted sleep-wake pattern and prioritize them for clinical diagnosis. Methods: This study used a dataset of 183 suspected OSA patients, of which 36 test subjects. First, a convolutional neural network was designed for sleep-wake classification based on healthier patients (AHI < 10). It employed single 30 s epochs of electrocardiograms and respiratory inductance plethysmograms. Sleep information and Total Sleep Time (TST) was derived for all patients using the short-term segments. Next, OSA patients were detected based on the average confidence of sleep predictions and the percentage of sleep-wake transitions in the predicted sleep architecture. Results: Sleep-wake classification on healthy, mild and moderate patients resulted in moderate κ scores of 0.51, 0.49, and 0.48, respectively. However, TST estimates decreased in accuracy with increasing AHI. Nevertheless, severe patients were detected with a sensitivity of 78% and specificity of 89%, and prioritized for clinical diagnosis. As such, their inaccurate TST estimate becomes irrelevant. Excluding detected OSA patients resulted in an overall estimated TST with a mean bias error of 21.9 (± 55.7) min and Pearson correlation of 0.74 to the reference. Conclusion: The presented framework offered a realistic tool for unobtrusive sleep monitoring of suspected OSA patients. Moreover, it enabled fast prioritization of severe patients for clinical diagnosis.

Technical aspects of cardiorespiratory estimation using subspace projections and cross entropy.

Background.Respiratory sinus arrhythmia (RSA) is a form of cardiorespiratory coupling. Its quantification has been suggested as a biomarker to diagnose different diseases. Two state-of-the-art methods, based on subspace projections and entropy, are used to estimate the RSA strength and are evaluated in this paper. Their computation requires the selection of a model order, and their performance is strongly related to the temporal and spectral characteristics of the cardiorespiratory signals.Objective.To evaluate the robustness of the RSA estimates to the selection of model order, delays, changes of phase and irregular heartbeats as well as to give recommendations for their interpretation on each case.Approach.Simulations were used to evaluate the model order selection when calculating the RSA estimates introduced before, as well as three different scenarios that can occur in signals acquired in non-controlled environments and/or from patient populations: the presence of irregular heartbeats; the occurrence of delays between heart rate variability (HRV) and respiratory signals; and the changes over time of the phase between HRV and respiratory signals.Main results.It was found that using a single model order for all the calculations suffices to characterize RSA correctly. In addition, the RSA estimation in signals containing more than 5 irregular heartbeats in a period of 5 min might be misleading. Regarding the delays between HRV and respiratory signals, both estimates are robust. For the last scenario, the two approaches tolerate phase changes up to 54°, as long as this lasts less than one fifth of the recording duration.Significance.Guidelines are given to compute the RSA estimates in non-controlled environments and patient populations.

Benchmarking Transfer Entropy Methods for the Study of Linear and Nonlinear Cardio-Respiratory Interactions.

Transfer entropy (TE) has been used to identify and quantify interactions between physiological systems. Different methods exist to estimate TE, but there is no consensus about which one performs best in specific applications. In this study, five methods (linear, k-nearest neighbors, fixed-binning with ranking, kernel density estimation and adaptive partitioning) were compared. The comparison was made on three simulation models (linear, nonlinear and linear + nonlinear dynamics). From the simulations, it was found that the best method to quantify the different interactions was adaptive partitioning. This method was then applied on data from a polysomnography study, specifically on the ECG and the respiratory signals (nasal airflow and respiratory effort around the thorax). The hypothesis that the linear and nonlinear components of cardio-respiratory interactions during light and deep sleep change with the sleep stage, was tested. Significant differences, after performing surrogate analysis, indicate an increased TE during deep sleep. However, these differences were found to be dependent on the type of respiratory signal and sampling frequency. These results highlight the importance of selecting the appropriate signals, estimation method and surrogate analysis for the study of linear and nonlinear cardio-respiratory interactions.

Linear and Non-linear Quantification of the Respiratory Sinus Arrhythmia Using Support Vector Machines.

Respiratory sinus arrhythmia (RSA) is a form of cardiorespiratory coupling. It is observed as changes in the heart rate in synchrony with the respiration. RSA has been hypothesized to be due to a combination of linear and nonlinear effects. The quantification of the latter, in turn, has been suggested as a biomarker to improve the assessment of several conditions and diseases. In this study, a framework to quantify RSA using support vector machines is presented. The methods are based on multivariate autoregressive models, in which the present samples of the heart rate variability are predicted as combinations of past samples of the respiration. The selection and tuning of a kernel in these models allows to solve the regression problem taking into account only the linear components, or both the linear and the nonlinear ones. The methods are tested in simulated data as well as in a dataset of polysomnographic studies taken from 110 obstructive sleep apnea patients. In the simulation, the methods were able to capture the nonlinear components when a weak cardiorespiratory coupling occurs. When the coupling increases, the nonlinear part of the coupling is not detected and the interaction is found to be of linear nature. The trends observed in the application in real data show that, in the studied dataset, the proposed methods captured a more prominent linear interaction than the nonlinear one.

Capacitively-coupled ECG and respiration for the unobtrusive detection of sleep apnea.

OBJECTIVE: The performance of a novel unobtrusive system based on capacitively-coupled electrocardiography (ccECG) combined with different respiratory measurements is evaluated for the detection of sleep apnea. APPROACH: A sleep apnea detection algorithm is proposed, which can be applied to electrocardiography (ECG) and ccECG, combined with different unobtrusive respiratory measurements, including ECG derived respiration (EDR), respiratory effort measured using the thoracic belt (TB) and capacitively-coupled bioimpedance (ccBioz). Several ECG, respiratory and cardiorespiratory features were defined, of which the most relevant ones were identified using a random forest based backwards wrapper. Using this relevant feature set, a least-squares support vector machine classifier was trained to decide if a one minute segment is apneic or not, based on the annotated polysomnography (PSG) data of 218 patients suspected of having sleep apnea. The obtained classifier was then tested on the PSG and capacitively-coupled data of 28 different patients. MAIN RESULTS: On the PSG data, an AUC of 76.3% was obtained when the ECG was combined with the EDR. Replacing the EDR with the TB led to an AUC of 80.0%. Using the ccECG and ccBioz or the ccECG and TB resulted in similar performances as on the PSG data, while using the ccECG and ccECG-based EDR resulted in a drop in AUC to 67.4%. SIGNIFICANCE: This is the first study which tests an apnea detection algorithm on capacitively-coupled ECG and bioimpedance signals and shows promising results on the capacitively-coupled data set. However, it was shown that the EDR could not be accurately estimated from the ccECG signals. Further research into the effect that respiration has on the ccECG is needed to propose alternative EDR estimates.

A Comparative Study of ECG-derived Respiration in Ambulatory Monitoring using the Single-lead ECG.

Cardiorespiratory monitoring is crucial for the diagnosis and management of multiple conditions such as stress and sleep disorders. Therefore, the development of ambulatory systems providing continuous, comfortable, and inexpensive means for monitoring represents an important research topic. Several techniques have been proposed in the literature to derive respiratory information from the ECG signal. Ten methods to compute single-lead ECG-derived respiration (EDR) were compared under multiple conditions, including different recording systems, baseline wander, normal and abnormal breathing patterns, changes in breathing rate, noise, and artifacts. Respiratory rates, wave morphology, and cardiorespiratory information were derived from the ECG and compared to those extracted from a reference respiratory signal. Three datasets were considered for analysis, involving a total 59 482 one-min, single-lead ECG segments recorded from 156 subjects. The results indicate that the methods based on QRS slopes outperform the other methods. This result is particularly interesting since simplicity is crucial for the development of ECG-based ambulatory systems.

Multilevel Interval Coded Scoring to Assess the Cardiovascular Status of Sleep Apnea Patients Using Oxygen Saturation Markers.

OBJECTIVE: Studies have shown an increased cardiovascular risk in obstructive sleep apnea (OSA) patients. In order to prioritize treatment of high risk patients, there is a need for improved cardiovascular OSA phenotyping. This study investigates the use of oxygen saturation (SpO 2) parameters for cardiovascular risk assessment of OSA patients. To this end, a novel multilevel interval coded scoring (mICS) algorithm is proposed. METHODS: The study includes SpO 2 recordings from 1987 overnight polysomnographies, of which 974 are from patients suspected to have OSA, 931 from the general population based Sleep Heart Health Study and 83 from healthy controls. The minimal SpO 2 value, SpO 2 upslope and amplitude ratio of desaturation over resaturation are extracted for all oxygen desaturations and averaged per patient. These three SpO 2 parameters are used together with patient demographics to develop a mICS model to predict the probability that a patient had a cardiovascular condition, or had already experienced a cardiovascular event, at the time of the polysomnography. RESULTS: Including the SpO 2 parameters in the mICS together with age and BMI improves the model's performance by 2.7% and leads to a test area under the curve (AUC) of 69.5% for the detection of any cardiovascular comorbidity. Moreover, an increase in AUC of 5% was obtained for the detection of cardiovascular events, resulting in an AUC of 93.5%. CONCLUSIONS: This study shows that parameters based on SpO 2 and the mICS model are useful to predict the cardiovascular comorbidity status of OSA patients. SIGNIFICANCE: The proposed model could be used to assist in prioritizing OSA patients for treatment.

Autonomic Dysfunction Increases Cardiovascular Risk in the Presence of Sleep Apnea.

The high prevalence of sleep apnea syndrome (SAS) and its direct relationship with an augmented risk of cardiovascular disease (CVD) have raised SAS as a primary public health problem. For this reason, extensive research aiming to understand the interaction between both conditions has been conducted. The advances in non-invasive autonomic nervous system (ANS) monitoring through heart rate variability (HRV) analysis have revealed an increased sympathetic dominance in subjects suffering from SAS when compared with controls. Similarly, HRV analysis of subjects with CVD suggests altered autonomic activity. In this work, we investigated the altered autonomic control in subjects suffering from SAS and CVD simultaneously when compared with SAS patients, as well as the possibility that ANS assessment may be useful for the early stage identification of cardiovascular risk in subjects with SAS. The analysis was performed over 199 subjects from two independent datasets during night-time, and the effects of the physiological response following an apneic episode, sleep stages, and respiration on HRV were taken into account. Results, as measured by HRV, suggest a decreased sympathetic dominance in those subjects suffering from both conditions, as well as in subjects with SAS that will develop CVDs, which was reflected in a significantly reduced sympathovagal balance (p < 0.05). In this way, ANS monitoring could contribute to improve screening and diagnosis, and eventually aid in the phenotyping of patients, as an altered response might have direct implications on cardiovascular health.

Evaluation of a Commercial Ballistocardiography Sensor for Sleep Apnea Screening and Sleep Monitoring.

There exists a technological momentum towards the development of unobtrusive, simple, and reliable systems for long-term sleep monitoring. An off-the-shelf commercial pressure sensor meeting these requirements is the Emfit QS. First, the potential for sleep apnea screening was investigated by revealing clusters of contaminated and clean segments. A relationship between the irregularity of the data and the sleep apnea severity class was observed, which was valuable for screening (sensitivity 0.72, specificity 0.70), although the linear relation was limited ( R 2 of 0.16). Secondly, the study explored the suitability of this commercial sensor to be merged with gold standard polysomnography data for future sleep monitoring. As polysomnography (PSG) and Emfit signals originate from different types of sensor modalities, they cannot be regarded as strictly coupled. Therefore, an automated synchronization procedure based on artefact patterns was developed. Additionally, the optimal position of the Emfit for capturing respiratory and cardiac information similar to the PSG was identified, resulting in a position as close as possible to the thorax. The proposed approach demonstrated the potential for unobtrusive screening of sleep apnea patients at home. Furthermore, the synchronization framework enabled supervised analysis of the commercial Emfit sensor for future sleep monitoring, which can be extended to other multi-modal systems that record movements during sleep.

Feature Selection Algorithm based on Random Forest applied to Sleep Apnea Detection.

This paper presents a new feature selection method based on the changes in out-of-bag (OOB) Cohen kappa values of a random forest (RF) classifier, which was tested on the automatic detection of sleep apnea based on the oxygen saturation signal (SpO2). The feature selection method is based on the RF predictor importance defined as the increase in error when features are permuted. This method is improved by changing the classification error into the Cohen kappa value, by adding an extra factor to avoid correlated features and by adapting the OOB sample selection to obtain a patient independent validation. When applying the method for sleep apnea classification, an optimal feature set of 3 parameters was selected out of 286. This was half of the 6 features that were obtained in our previous study. This feature reduction resulted in an improved interpretability of our model, but also a slight decrease in performance, without affecting the clinical screening performance. Feature selection is an important issue in machine learning and especially biomedical informatics. This new feature selection method introduces interesting improvements of RF feature selection methods, which can lead to a reduced feature set and an improved classifier interpretability.

Automatic Screening of Sleep Apnea Patients Based on the SpO2 Signal.

OBJECTIVE: This paper presents a methodology to automatically screen for sleep apnea based on the detection of apnea and hypopnea events in the blood oxygen saturation (SpO2) signal. METHODS: It starts by detecting all desaturations in the SpO2 signal. From these desaturations, a total of 143 time-domain features are extracted. After feature selection, the six most discriminative features are used to construct classifiers to predict if desaturations are caused by respiratory events. From these, a random forest classifier yielded the best classification performance. The number of desaturations, classified as caused by respiratory events per hour of recording, can then be used as an estimate of the apnea-hypopnea index (AHI), and to predict whether or not a patient suffers from sleep apnea-hypopnea syndrome (SAHS). All classifiers were developed based on a subset of 500 subjects of the Sleep Heart Health Study (SHHS) and tested on three different datasets, containing 8052 subjects in total. RESULTS: An averaged desaturation classification accuracy of 82.8% was achieved over the different test sets. Subjects having SAHS with an AHI greater than 15 can be detected with an average accuracy of 87.6%. CONCLUSION: The achieved SAHS screening outperforms SpO2 methods from the literature on the SHHS test dataset. Moreover, the robustness of the method was shown when tested on different independent test sets. SIGNIFICANCE: These results show that an algorithm based on simple features of SpO2 desaturations can outperform more elaborate methods in the detection of apneic events and the screening of SAHS patients.

Adherence to CPAP therapy: comparing the effect of three educational approaches in patients with obstructive sleep apnoea.

INTRODUCTION: Continuous positive airway pressure (CPAP)-therapy is the first-line treatment for moderate to severe obstructive sleep apnoea (OSA). A significant limitation of CPAP treatment is the poor therapy adherence, compromising the beneficial effects. OBJECTIVE: This study evaluates three different educational approaches and their effect on therapy adherence. METHOD: This single-center, retrospective study compared three groups of 100 consecutive, CPAP-naive patients with moderate to severe OSA who were started on CPAP therapy. Group 1 and 2 received the same individual structured education on two consecutive days with an extra phone call 7 to 10 days after CPAP start in group 2. Group 3 received individual structured education on the first day and participated in a group education using a slide presentation open for discussion on the second day. Re-evaluation was performed after 24 weeks. RESULTS: Baseline characteristics did not differ significantly between groups. During the 24 weeks follow-up there was a drop-out rate of 16% (group 1), 12% (group 2) and 5% (group 3). In the patients still on CPAP after 24 weeks, the mean nightly CPAP usage was, respectively, 4.7 ± 1.8, 5.2 ± 2.3 and 5.7 ± 2.1 h/night. In group 3 both the drop-out rate and mean CPAP usage were significantly different (P values, respectively, P < 0.05 and P < 0.01) compared with group 1. CONCLUSION: Improving CPAP adherence is an ongoing challenge. This study shows that a multi-modality approach, using a combination of individual and group education using a slide presentation open for discussion resulted in improved therapy adherence.