Proof-of-concept for characterization of neurodegenerative disorders utilizing two non-REM sleep biomarkers.

Study objective: This proof-of-concept study aimed to determine whether the combined features of two non-rapid eye movement (NREM) sleep biomarkers acquired predominantly in-home could characterize different neurodegenerative disorders. Methods: Sleep spindle duration and non-REM hypertonia (NRH) were evaluated in seven groups including a control group (CG = 61), and participants with isolated REM sleep behavior disorder (iRBD = 19), mild cognitive impairment (MCI = 41), Parkinson disease (PD = 16), Alzheimer disease dementia (ADem = 29), dementia with Lewy Bodies or Parkinson disease dementia (LBD = 19) and progressive supranuclear palsy (PSP = 13). One-way analysis of variance (ANOVA), Mann-Whitney U, intra-class (ICC) and Spearman ranked correlations, Bland-Altman plots and Kappa scores, Chi-square and Fisher exact probability test, and multiple-logistic regression were focused primarily on spindle duration and NRH and the frequencies assigned to the four normal/abnormal spindle duration/NRH combinations. Results: ANOVA identified group differences in age, sleep efficiency, REM, NRH (p < 0.0001) and sleep time (p = 0.015), Spindle duration and NRH each demonstrated good night-to-night reliabilities (ICC = 0.95 and 0.75, Kappa = 0.93 and 0.66, respectively) and together exhibited an association in the PD and LBD groups only (p < 0.01). Abnormal spindle duration was greater in records of PSP (85%) and LBD (84%) patients compared to CG, MCI, PD and ADem (p < 0.025). Abnormal NRH was greater in PSP = 92%, LBD = 79%, and iRBD = 74% compared to MCI = 32%, ADem = 17%, and CG = 16% (p < 0.005).The combination biomarker normal spindle duration/normal NRH was observed most frequently in CG (56%) and MCI (41%). ADem most frequently demonstrated normal spindle duration/normal NRH (45%) and abnormal spindle duration/normal NRH (38%). Normal spindle duration/abnormal NRH was greatest in iRBD = 47%, while abnormal spindle duration/abnormal NRH was predominant in PSP = 85% and LBD = 74%. Conclusion: The NREM sleep biomarkers spindle duration and NRH may be useful in distinguishing patients with different neurodegenerative disorders. Larger prospective cohort studies are needed to determine whether spindle duration and NRH can be combined for prodromal assessment and/or monitoring disease progression.

Autonomic dysregulation during sleep in Parkinsonian spectrum disorders - A proof of concept.

INTRODUCTION: Autonomic dysfunction is common in α-synucleinopathies such as Lewy Body dementias (LBD), Parkinson's disease (PD), and isolated REM Sleep Behavior Disorder (iRBD). We analyzed pulse-rate changes during sleep to index autonomic nervous system (ANS) dysfunction in patients with α-synucleinopathies vs. non-synucleinopathy groups expected to have normal ANS function. METHODS: Patients with LBD (n = 16), PD (PD, n = 14) or iRBD (n = 12) were compared to the non-synucleinopathy groups Alzheimers disease dementia (ADem, n = 26), mild cognitive impairment (MCI, n = 34) or controls (CG, n = 54). Sleep Profiler was used to derive a sleep autonomic activation index (AAI), i.e., ≥6 beat-per-minute increase/decrease, pulse rate coefficient of variation (PR-CV), and automated sleep staging with sleep-spindles and non-REM hypertonia (NRH). Analysis included statistical group comparisons and receiver operating characteristics curves to determine optimal classification of groups. RESULTS: AAI and PR-CV were moderately correlated across all recordings (rs = 0.58, P < 0.0001), except in the LBD and PD groups. AAI but not PR-CV differentiated the LBD, PD and iRBD from non-Parkinsonian groups. AAI was decreased in LBD and PD patients compared to the CG (p < 0.003) and MCI (p < 0.03). AAI decreased based on age and its receiver operating characteristic area under the curve ranged from 0.63 to 0.75. AAI had a weak negative correlation to NRH (rs ≤ -0.26) but not sleep-spindles. CONCLUSION: Synucleinopathy-related ANS dysfunction can reasonably discriminate prodromal and manifest PD/LBD diseased groups from non-synucleinopathies. Further studies incorporating AAI into a multivariate classifier of neurodegenerative disorders based on sleep characteristics acquired in the patient's home are planned.

The Accuracy and Reliability of Sleep Staging and Sleep Biomarkers in Patients with Isolated Rapid Eye Movement Sleep Behavior Disorder.

Purpose: This study aimed to establish the diagnostic accuracy of a previously validated sleep staging system in patients with probable isolated REM sleep behavior disorder (iRBD), and to compare physicians' diagnoses of iRBD based on REM sleep without atonia (RSWA) to non-REM hypertonia (NRH), a sleep measure independently associated with Parkinsonian spectrum disorders. Patients and Methods: Twenty-six patients with a history of dream enactment behavior underwent a diagnostic PSG with simultaneous Sleep Profiler (SP) acquisition at two sites. PSG and SP records were sleep staged, and two sleep neurologists independently diagnosed iRBD based on the presence or absence of polysomnographic identified RSWA. Comparisons for PSG vs SP sleep staging and the qualitative presence or absence of PSG-based RSWA vs automated SP-detected NRH was performed using kappa coefficients (k), positive and negative percent agreements (PPA and NPA), and chi-square tests. Results: The kappa scores from Sites-1 and -2 for PSG vs SP staging were different for Wake (k=0.82 vs 0.65), N2 (k=0.63 vs 0.72) and REM (k=0.83 vs.0.72). The by-site kappa values for stage N3 increased from 0.72 and 0.37 to 0.88 and 0.74 after PSG records were reedited. The kappa values for between-physician agreement in iRBD diagnoses were fair (k = 0.22). The agreement between each physician's iRBD diagnoses and NRH were also fair (k=0.29 and 0.22). Abnormal NRH agreed with at least one physician's iRBD diagnosis in 83% of the records. The PPA resulting from between-physician iRBD agreement was stronger and the NPA weaker than the values obtained from comparison of each physician's iRBD diagnosis and abnormal NRH. Conclusion: The potential utility of RSWA and stage N3 as neurodegenerative disorder biomarkers was influenced by between-site variability in visual scoring. The degree to which NRH was associated with iRBD was similar to the between-physician agreement in their diagnosis of iRBD using RSWA.

Non-REM sleep with hypertonia in Parkinsonian Spectrum Disorders: A pilot investigation.

INTRODUCTION: From an ongoing multicenter effort toward differentiation of Parkinsonian spectrum disorders (PSD) from other types of neurodegenerative disorders, the sleep biomarker non-rapid-eye-movement sleep with hypertonia (NRH) emerged. METHODS: This study included in the PSD group patients with dementia with Lewy bodies/Parkinson disease dementia (DLB/PDD = 16), Parkinson disease (PD = 16), and progressive supranuclear palsy (PSP = 13). The non-PSD group included patients with Alzheimer disease dementia (AD = 24), mild cognitive impairment (MCI = 35), and a control group with normal cognition (CG = 61). In-home, multi-night Sleep Profiler studies were conducted in all participants. Automated algorithms detected NRH, characterized by elevated frontopolar electromyographic power. Between-group differences in NRH were evaluated using Logistic regression, Mann-Whitney U and Chi-squared tests. RESULTS: NRH was greater in the PSD group compared to non-PSD (13.9 ± 11.0% vs. 3.1 ± 4.7%, P < 0.0001). The threshold NRH≥5% provided the optimal between-group differentiation (AUC = 0.78, P < 0.001). NRH was independently associated with the PSD group after controlling for age, sex, and SSRI/SNRI use (P < 0.0001). The frequencies of abnormal NRH by subgroup were PSP = 92%, DLB/PDD = 81%, PD = 56%, MCI = 26%, AD = 17%, and CG = 16%. The odds of abnormal NRH in each PSD subgroup ranged from 3.7 to 61.2 compared to each non-PSD subgroup. The night-to-night and test-retest intraclass correlations were excellent (0.78 and 0.84, both P < 0.0001). CONCLUSIONS: In this pilot study, NRH appeared to be a novel candidate sleep biomarker for PSD-related neurodegeneration. Future studies in larger cohorts are needed to confirm these findings, understand the etiology of NRH magnitude/duration, and determine whether it is an independent prodromal marker for specific neurodegenerative pathologies.

Criteria for oral appliance and/or supine avoidance therapy selection based on outcome optimization and cost-effectiveness.

AIM: Produce empirical support for further enhancements to a therapy selection protocol for obstructive sleep apnea (OSA) patients intolerant of positive airway pressure. METHODS: A retrospective analysis was conducted in 101 men and 69 women patients. Two-night home sleep apnea studies were conducted at baseline and with a trial oral appliance. Twenty-minutes in-position sleep was required to compute supine and non-supine apnea-hypopnea indexes (AHI). Data analyses were applied after stratification by sex and response to oral appliance therapy (OAT), and the results used for to calculate incremental cost-effectiveness ratios (ICER). RESULTS: Compared with men, women had significantly lower pre-treatment supine and non-supine AHI values (p < .05). OAT non-responders had higher non-supine AHIs, resulting in less positional-OSA and more cases with severe OSA (p < .05). Across the cohort, 21% had positional-OSA with a pre-treatment non-supine AHI < 5 events/h. In those who met this criterion, supine avoidance therapy (SAT) could have reduced the AHI values more than OAT by an average of 33% (p < .0001). The ICER for SAT instead of OAT in this group was negative, a condition that only occurs when one therapy is both less expensive and more effective than the other. A greater proportion of non-responders had post-OAT overall AHI ≥ 10 events/h with residual positional-OSA compared with responders (p < .0001). Combination therapy could reduce the AHI values by an average of 68%, resulting in ICER estimates five-times less than the reimbursement decision-making threshold. CONCLUSIONS AND LIMITATIONS: Based on pre-treatment non-supine AHI values, SAT would provide a superior first-line treatment outcome as compared to OAT in 21% of patients diagnosed with OSA. SAT would also provide a cost-effective adjuvant to OAT in an additional 15% of cases. The benefit of SAT could not be determined in one-fifth of the cohort who slept exclusively supine.

A comparison between auto-scored apnea-hypopnea index and oxygen desaturation index in the characterization of positional obstructive sleep apnea.

OBJECTIVE: Evaluate the concordance between overall and positional oxygen desaturation indices (ODI) and apnea-hypopnea indices (AHI) according to two different definitions for positional obstructive sleep apnea (POSA). METHODS: A total of 184 in-home polysomnograms were edited to simulate Level III home sleep apnea tests (HSAT) with the auto-scored AHI and ODI based on recording time. POSA was determined using 132 records with an AHI≥5 and at least 20 mins of recording time in both supine and non-supine positions. POSA was defined independently for the AHI and ODI based on ratios of overall/non-supine event/h ≥1.4 (O/NS) and supine/non-supine event/h≥2.0 (S/NS). RESULTS: Correlation between the AHI and ODI was 0.97 overall, 0.94 for supine, and 0.96 for non-supine recording times (all p<0.001). For most records, differences between the AHI and ODI were small, with only 14% of the records having a AHI-ODI difference exceeding >5/hr, and 6% exceeding >10 events/hr. The positive and negative percent agreements were uniformly good to excellent across varying clinical POSA cutoffs; percent agreements (positive, negative) were: AHI≥5=0.99, 0.78; AHI≥10=0.96, 0.89; and AHI≥15=0.96, 0.89. Cohen's Kappa scores also showed substantial agreement for overall as well as supine and non-supine positions across varying clinical cutoffs of the AHI. Frequency of POSA was reproducibly uniform between 59% and 61% for both POSA criteria. When the O/NS and S/NS definitions conflicted in POSA characterization, O/NS was superior for identifying patients who might exhibit a greater response to supine restriction positional therapy. CONCLUSIONS: Auto-scored positional oximetry is a clinically viable alternative to an auto-scored Level III HSAT AHI in the characterization of POSA based on a 3% desaturation.

Head Position During Sleep: Potential Implications for Patients with Neurodegenerative Disease.

BACKGROUND: The characterization of sleep in those with neurodegenerative disease (NDD) is essential in understanding the potential neurobiological mechanisms that underlie the connection between sleep disruption and NDD manifestations and progression. OBJECTIVE: Explore the inter-relationships between NDD and age, sex, diagnosis of obstructive sleep apnea, snoring, and duration of sleep time with the head in the supine and non-supine positions. METHODS: A case-control design was used to evaluate differences in sleep position obtained from multi-night, in-home Sleep Profiler recordings in 45 patients with diagnosed NDD (24 with mild cognitive impairment, 15 with Alzheimer's disease, and 6 with Lewy Body, Parkinson's, or other dementias) and 120 age-sex matched controls with normal cognition (NC). RESULTS: The frequency of supine sleep >2 h/night was significantly greater in the NDD than in the NC group (p < 0.001, odds ratio = 3.7), and remained significant after controlling for age, sex, snoring, and obstructive sleep apnea diagnosis (p = 0.01). There were no group differences in nocturnal mobility i.e., number of head position changes/h. CONCLUSION: This study demonstrates the utility of in-home measurements of sleep in defining the association of supine sleep position with neurodegenerative disorders. Our findings warrant further investigation, particularly in light of the recent evidence suggesting that sleep may an active role in the brain's ability to clear CNS neurotoxins and metabolites.

Comparison of EMG power during sleep from the submental and frontalis muscles.

OBJECTIVE: Submentalis electromyography (sEMG) and frontalis electromyography (fEMG) muscle activities have been used to assist in the staging of sleep and detection of disruptions in sleep. This study was designed to assess the concordance between sEMG and fEMG power, by and across sleep stages. METHODS: Forty-three records with simultaneous acquisition of differential signals from the submental and frontalis muscles were evaluated. Sleep stages were assigned using the poly-somnography signals based on majority agreement of five technicians. The sEMG and fEMG signals were identically filtered and aligned prior to cross-correlation analysis. RESULTS: A strong concordance between sEMG and fEMG power was observed, with 95% of the records exhibiting at least moderate agreement. During rapid eye movement (REM) sleep, sEMG power was significantly less than fEMG power, but exhibited four times greater across-subject variability. fEMG power during wake and non-REM (NREM) sleep was greater than sEMG power, but with 50% less variability. Differences in wake and N1 mean power and between the other sleep stages were more distinct in the fEMG recordings. Relative changes in sEMG and fEMG power across wake, NREM, and REM stages were essentially identical with median by-subject cross correlations of 0.98 and interquartile ranges of 0.97 and 0.99, respectively. CONCLUSION: The fEMG and sEMG power values were similar during wakefulness and sleep; however, the frontalis exhibits substantially less between-subject variability. This study established face validity for the use of fEMG in the detection of wake and stages of sleep, and for future applications toward assessment of quantitative REM sleep muscle activity in REM sleep behavior disorder.

A systematic comparison of factors that could impact treatment recommendations for patients with Positional Obstructive Sleep Apnea (POSA).

OBJECTIVE/BACKGROUND: Systematically compare four criteria for Positional Obstructive Sleep Apnea (POSA) based on AASM 2007 and 2012 hypopnea scoring definitions. PATIENTS/METHODS: 142 records acquired by in-home polysomnography (Sleep Profiler PSG2™) were retrospectively analyzed using AHI based on the American Academy Sleep Medicine 2007 and 2012 criteria (AHI2007 and AHI2012). Positional obstructive sleep apnea (POSA) was characterized using four criteria: Amsterdam Positional OSA Classification (APOC), supine AHI twice the non-supine AHI (Cartwright), Cartwright plus the non-supine AHI < 5 (Mador), and the overall AHI severity at least 1.4 times the non-supine severity (Overall/NS-AHI). RESULTS: Correlations between the Cartwright and Overall/NS-AHI criteria increased with the inclusion of a more relaxed definition of hypopneas (AHI2007 = 0.79 and AHI2012 = 0.86, P < 0.00001). The prevalence of POSA based on the Cartwright and Overall/NS-AHI criteria was approximately 60% in those with at least mild OSA by AHI2007and AHI2012. A 16% reduction in POSA prevalence for AHI2012 vs. AHI2007 was attributed to the increased incident of mild OSA. For identification of those expected to have 25% or 35% reductions in SDB severity with positional therapy, Cartwright and Overall/NS-AHI exhibited the strongest sensitivity and Overall/NS-AHI and Mador the best specificity. CONCLUSIONS: The four criteria used to identify POSA have similarities and differences. While there were similarities between the Cartwright and Overall/NS-AHI criteria in the detection of POSA prevalence across both scoring criteria, the Overall/NS-AHI provided the most consistent detection of those most likely to demonstrate important reductions in sleep disordered breathing severity if supine sleep is avoided.

The Accuracy, Night-to-Night Variability, and Stability of Frontopolar Sleep Electroencephalography Biomarkers.

STUDY OBJECTIVES: To assess the validity of sleep architecture and sleep continuity biomarkers obtained from a portable, multichannel forehead electroencephalography (EEG) recorder. METHODS: Forty-seven subjects simultaneously underwent polysomnography (PSG) while wearing a multichannel frontopolar EEG recording device (Sleep Profiler). The PSG recordings independently staged by 5 registered polysomnographic technologists were compared for agreement with the autoscored sleep EEG before and after expert review. To assess the night-to-night variability and first night bias, 2 nights of self-applied, in-home EEG recordings obtained from a clinical cohort of 63 patients were used (41% with a diagnosis of insomnia/depression, 35% with insomnia/obstructive sleep apnea, and 17.5% with all three). The between-night stability of abnormal sleep biomarkers was determined by comparing each night's data to normative reference values. RESULTS: The mean overall interscorer agreements between the 5 technologists were 75.9%, and the mean kappa score was 0.70. After visual review, the mean kappa score between the autostaging and five raters was 0.67, and staging agreed with a majority of scorers in at least 80% of the epochs for all stages except stage N1. Sleep spindles, autonomic activation, and stage N3 exhibited the least between-night variability (P < .0001) and strongest between-night stability. Antihypertensive medications were found to have a significant effect on sleep quality biomarkers (P < .02). CONCLUSIONS: A strong agreement was observed between the automated sleep staging and human-scored PSG. One night's recording appeared sufficient to characterize abnormal slow wave sleep, sleep spindle activity, and heart rate variability in patients, but a 2-night average improved the assessment of all other sleep biomarkers. COMMENTARY: Two commentaries on this article appear in this issue on pages 771 and 773.

Capability of a neck worn device to measure sleep/wake, airway position, and differentiate benign snoring from obstructive sleep apnea.

To evaluate the accuracy of a neck-worn device in measuring sleep/wake, detecting supine airway position, and using loud snoring to screen for obstructive sleep apnea. Study A included 20 subjects who wore the neck-device during polysomnography (PSG), with 31 records obtained from diagnostic and split-night studies. Study B included 24 community-based snorers studied in-home for up to three-nights with obstructive sleep apnea (OSA) severity measured with a validated Level III recorder. The accuracy of neck actigraphy-based sleep/wake was measured by assessing sleep efficiency (SE). Differences in sleep position measured at the chest and neck during PSG were compared to video-editing. Loud snoring acquired with an acoustic microphone was compared to the apnea-hypopnea index (AHI) by- and acrosspositions. Over-reported SE by neck actigraphy was inversely related to OSA severity. Measurement of neck and chest supine position were highly correlated with video-edits (r=0.93, 0.78). Chest was bias toward over-estimating supine time while the majority of neck-device supine position errors occurred during CPAP titrations. Snoring was highly correlated with the overall, supine, and non-supine PSG-AHI (r=0.79, 0.74, 0.83) and was both sensitive and specific in detecting overall, supine, and non-supine PSGAHI>10 (sensitivity=81, 88, 82%; specificity=87, 79, 100%). At home sleep testing-AHI>10, the sensitivity and specificity of loud snoring was superior when users were predominantly non-supine as compared to baseline (sensitivity=100, 92%; specificity=88, 77%). Neck actigraphy appears capable of estimating sleep/wake. The accuracy of supine airway detection with the neck-device warrants further investigation. Measurement of loud snoring appears to provide a screening tool for differentiating positional apneic and benign snorers.

Modeling temporal sequences of cognitive state changes based on a combination of EEG-engagement, EEG-workload, and heart rate metrics.

The objective of this study was to investigate the feasibility of physiological metrics such as ECG-derived heart rate and EEG-derived cognitive workload and engagement as potential predictors of performance on different training tasks. An unsupervised approach based on self-organizing neural network (NN) was utilized to model cognitive state changes over time. The feature vector comprised EEG-engagement, EEG-workload, and heart rate metrics, all self-normalized to account for individual differences. During the competitive training process, a linear topology was developed where the feature vectors similar to each other activated the same NN nodes. The NN model was trained and auto-validated on combat marksmanship training data from 51 participants that were required to make "deadly force decisions" in challenging combat scenarios. The trained NN model was cross validated using 10-fold cross-validation. It was also validated on a golf study in which additional 22 participants were asked to complete 10 sessions of 10 putts each. Temporal sequences of the activated nodes for both studies followed the same pattern of changes, demonstrating the generalization capabilities of the approach. Most node transition changes were local, but important events typically caused significant changes in the physiological metrics, as evidenced by larger state changes. This was investigated by calculating a transition score as the sum of subsequent state transitions between the activated NN nodes. Correlation analysis demonstrated statistically significant correlations between the transition scores and subjects' performances in both studies. This paper explored the hypothesis that temporal sequences of physiological changes comprise the discriminative patterns for performance prediction. These physiological markers could be utilized in future training improvement systems (e.g., through neurofeedback), and applied across a variety of training environments.

Assessment of a neck-based treatment and monitoring device for positional obstructive sleep apnea.

STUDY OBJECTIVES: A majority of patients diagnosed with obstructive sleep apnea are position dependent whereby they are at least twice as severe when sleeping supine (POSA). This study evaluated the accuracy and efficacy of a neck-worn device designed to limit supine sleep. The study included nightly measurements of snoring, sleep/wake, time supine, and the frequency and duration of feedback to monitor compliance. METHODS: Thirty patients between ages 18 and 75 years, BMI ≤ 35 with an overall apnea-hypopnea index (AHI) ≥ 5 and an overall AHI ≥ 1.5 times the non-supine AHI, and an Epworth score ≥ 5 were prospectively studied. Subjective reports and polysomnography were used to assess efficacy resulting from 4 weeks of in-home supine-avoidance therapy and to measure device accuracy. From 363 polysomnography reports, 209 provided sufficient positional data to estimate one site's prevalence of positional OSA. RESULTS: In 83% of participants exhibiting > 50% reduction in overall AHI, the mean and median reductions were 69% and 79%. Significant reductions in the overall and supine AHI, apnea index, percent time SpO2 < 90%, and snoring contributed to significant improvements in stage N1 and N2 sleep, reductions in cortical arousals and awakenings, and improved depression scores. Supine position was under-detected by > 5% in 3% of cases. Sleep efficiency by neck actigraphy was within 10% of polysomnography in 87% of the studies when position feedback was delivered. The prevalence of POSA was consistently > 70% when the overall AHI was < 60. CONCLUSIONS: The neck position therapy device is accurate and effective in restricting supine sleep, improving AHI, sleep architecture and continuity, and monitoring treatment outcomes.

Retrospective cross-validation of automated sleep staging using electroocular recording in patients with and without sleep disordered breathing.

BACKGROUND: Alterations of sleep duration and architecture have been associated with increased morbidity and mortality, and specifically linked to chronic cardiovascular disease and psychiatric disorders, such as type 2 diabetes or depression. Measurement of sleep quality to assist in the diagnosis or treatment of these diseases is not routinely performed due to the complexity and cost of conventional methods. The objective of this study is to cross-validate the accuracy of an automated algorithm that stages sleep from the EEG signal acquired with sensors that can be self-applied by patients. METHODS: This retrospective study design included polymsomnographic records from 19 presumably healthy individuals and 68 patients suspected of having sleep disordered breathing (SDB). Epoch-by-epoch comparisons were made between manual vs. automated sleeps staging (from the left and right electrooculogram) with the impact of SDB severity considered. RESULTS: Both scoring methods reported decreased Stage N3 and REM and increased wake and N1 as SDB severity increased. Inter-class correlations and Kappa coefficients were strong across all stages except N1. Agreements across all epochs for subjects with normal and patients with mild SDB were: wake = 80%, N1 = 25%, N2 = 78%, N3 = 84% and REM = 75%. Agreement decreased in patients with moderate and severe SDB amounting to: wake = 71%, N1 = 30%, N2 = 71%, N3 = 65%, and REM = 67%. Differences in detection of sleep onset were within three-minutes in 48 % of the subjects and 10-min in 73 % of the cases and were not impacted by SDB severity. Automated staging slightly underestimated total sleep time but this difference had a limited impact on the respiratory disturbance indexes. CONCLUSIONS: This cross-validation study demonstrated that measurement of sleep architecture obtained from a single-channel of forehead EEG can be equivalent to between-rater agreement using conventional manual scoring. The accuracies obtained with automated sleep staging were inversely proportional to SDB severity at a rate similar to manual scorers. These results suggest that the automated sleep staging used in this study may prove useful in evaluating sleep quality in patients with chronic diseases.

Initial Evaluation of a Titration Appliance for Temporary Treatment of Obstructive Sleep Apnea.

BACKGROUND: Custom oral appliances that adjustably advance the mandible provide superior outcomes when treating patients with moderate or severe sleep apnea. Custom appliances, however, are expensive, must be fitted by a dentist, and the likelihood of successful outcomes are difficult to predict. An inexpensive trial appliance, if proven efficacious, might be used to predict custom appliance outcomes or to provide temporary therapeutic benefit. OBJECTIVE: The aim of this initial study was to assess the treatment efficacy of a novel titration oral appliance with that of an optimized custom appliance. METHODS: Seventeen patients, treated with a custom oral appliance for at least one year, successfully completed a three-night home sleep test. The baseline obstructive sleep apnea severity was established on Night 1 with seven patients exhibiting severe, six moderate and four mild apnea/hypopnea indexes. Patients were randomly assigned to wear their custom appliance or the titration appliance on Nights 2 and 3. RESULTS: Significant reductions in the mean overall and supine apnea indexes (p < 0.05), and the overall (p < 0.01) and supine (p < 0.05) apnea/hypopnea indexes were observed for both the titration and custom appliances. The proportion of patients who exhibited at least a 50% reduction in the overall apnea index and supine apnea/hypopnea were similar for the titration and custom appliance (~60%). The custom appliance reduced the overall apnea/hypopnea index by 50% in a greater proportion of the patients compared to the titration appliance (77% vs. 53%). The titration appliance significantly reduced the degree of hypoxic exposure across sleep disordered breathing events overall (p < 0.05) and supine (p < 0.01). Patients found their custom appliance was more comfortable than the titration appliance, but preferred the titration appliance to no therapy. CONCLUSION: The titration appliance may be useful in assessing oral appliance treatment efficacy. When set to 70% of maximum protrusion, the titration appliance may provide immediate, temporary therapeutic benefit.

EEG-derived estimators of present and future cognitive performance.

Previous electroencephalography (EEG)-based fatigue-related research primarily focused on the association between concurrent cognitive performance and time-locked physiology. The goal of this study was to investigate the capability of EEG to assess the impact of fatigue on both present and future cognitive performance during a 20-min sustained attention task, the 3-choice active vigilance task (3CVT), that requires subjects to discriminate one primary target from two secondary non-target geometric shapes. The current study demonstrated the ability of EEG to estimate not only present, but also future cognitive performance, utilizing a single, combined reaction time (RT), and accuracy performance metric. The correlations between observed and estimated performance, for both present and future performance, were strong (up to 0.89 and 0.79, respectively). The models were able to consistently estimate "unacceptable" performance throughout the entire 3CVT, i.e., excessively missed responses and/or slow RTs, while acceptable performance was recognized less accurately later in the task. The developed models were trained on a relatively large dataset (n = 50 subjects) to increase stability. Cross-validation results suggested the models were not over-fitted. This study indicates that EEG can be used to predict gross-performance degradations 5-15 min in advance.

Drowsiness/alertness algorithm development and validation using synchronized EEG and cognitive performance to individualize a generalized model.

A great deal of research over the last century has focused on drowsiness/alertness detection, as fatigue-related physical and cognitive impairments pose a serious risk to public health and safety. Available drowsiness/alertness detection solutions are unsatisfactory for a number of reasons: (1) lack of generalizability, (2) failure to address individual variability in generalized models, and/or (3) lack of a portable, un-tethered application. The current study aimed to address these issues, and determine if an individualized electroencephalography (EEG) based algorithm could be defined to track performance decrements associated with sleep loss, as this is the first step in developing a field deployable drowsiness/alertness detection system. The results indicated that an EEG-based algorithm, individualized using a series of brief "identification" tasks, was able to effectively track performance decrements associated with sleep deprivation. Future development will address the need for the algorithm to predict performance decrements due to sleep loss, and provide field applicability.

Patients with positional versus nonpositional obstructive sleep apnea: a retrospective study of risk factors associated with apnea-hypopnea severity.

OBJECTIVE: The aim of this study was to investigate the differences in and risk factors for positional and nonpositional obstructive sleep apnea (OSA). STUDY DESIGN: One hundred twenty-three nonpositional (supine apnea-hypopnea index [AHI] < 2 times the lateral AHI), 218 positional (supine AHI ≥ 2 times the lateral AHI), and 109 age-, gender-, and BMI-matched patients with positional OSA performed 2 nights of sleep study. Gender, age, BMI, and percentage of time in supine position, and percentage of time snoring louder than 40 dB were evaluated as risk factors. RESULTS: Both unmatched positional and matched positional patients had less severe overall AHI values, higher mean SpO(2), lower percentage time SpO(2) less than 90%, and lower percentage of time snoring when compared with the nonpositional group. Overall AHI scores were associated with increasing age and percentage of time snoring for positional and nonpositional groups. However, BMIs were associated with the overall AHI only in the nonpositional group. CONCLUSION: The influence of position on OSA severity may contribute to the choice and prognosis of treatment and may represent 2 distinct groups with probable anatomic differences.

Treatment outcomes of mandibular advancement devices in positional and nonpositional OSA patients.

OBJECTIVE: The aim of the study was to investigate treatment outcome of mandibular advancement devices (MADs) for positional and nonpositional obstructive sleep apnea (OSA). STUDY DESIGN: Forty-two positional (supine apnea-hypopnea index [AHI] > or = 2 times lateral AHI) and 30 nonpositional (supine AHI < 2 times lateral AHI) OSA patients performed 2-nights of sleep study before and after insertion of MADs. RESULTS: The decreases in apnea severity based on a reduction in the overall and supine AHI values after MADs therapy were significantly greater for the positional OSA than nonpositional OSA group. A multiple linear regression analysis showed that decrease in overall AHI was significantly associated with being in the positional group (standardized coefficient = 0.505). Age, body mass index, gender, and time in supine position during sleep did not show significant associations with decrease in overall AHI after MAD therapy. CONCLUSION: Our data suggest that MADs are more effective in positional OSA than nonpositional OSA patients.

Validation of forehead venous pressure as a measure of respiratory effort for the diagnosis of sleep apnea.

OBJECTIVES: The aim of the study was to validate the measurement of Forehead Venous Pressure derived from a single site on the forehead as an alternative to esophageal manometry and respiratory effort bands in the differential diagnosis of sleep apnea. METHODS: Fourteen subjects underwent a laboratory polysomnography concurrently with ARES Unicorder at Walter Reed Army Medical Center. Two-hundred respiratory events were selected by a scorer boarded in sleep medicine and classified into six event categories used in the differential diagnosis of sleep disordered breathing. Four sets of events were prepared, each containing airflow and one of four measures of respiratory effort (i.e., esophageal manometer, chest and abdomen bands, and forehead venous pressure). A second board-certified scorer scored each set of events twice while blinded to the type of the effort signal. RESULTS: The inter-rater Kappa scores across all event types indicated all four effort signals provided moderate agreement (kappa = 0.43-0.47). When comparing the intra-rater Kappa scores, the chest belt was superior (kappa = 0.88) to the esophageal manometry, FVP and abdomen belt (kappa = 0.78-0.82). The Kappa scores for the intra-rater comparison with the esophageal serving as the gold standard, FVP abdomen and chest all showed near perfect agreement (kappa = 0.81-0.86). The esophageal manometer and FVP provided slightly better inter-rater agreement in the detection of both obstructive hypopneas and apneas as compared to the chest and abdomen belts. There was a 20-30% drop in inter-rater reliability in the detection of flow-limitation and ventilation-change events compared to obstructive events, and all effort signals showed poor inter-rater agreement for central and mixed events. CONCLUSIONS: The results of the study suggest that the FVP can serve as an alternative to respiratory bands in the differential diagnosis of sleep disordered breathing, and in the recognition of patients appropriate for bilevel continuous positive airway pressure devices.