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

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

The impact of alcohol consumption on commercial eye blink drowsiness detection technology.

INTRODUCTION: Driver drowsiness detection technology that assesses eye blinks is increasingly being used as a safety intervention in the transport industry. It is unclear how alcohol consumption to common legal driving limits impacts upon this technology. The aim of the study was to assess the impact of a blood alcohol content (BAC) of 0.05% and of 0.08% on drowsiness detection technology during simulated driving. METHODS: Participants completed a 60-min driving simulation and sleepiness questionnaire under three conditions: 1-0.00% BAC, 2-0.05% BAC and 3-0.08% BAC. During the driving simulation task participants wore a commercial eye blink drowsiness detection technology (Optalert) with the drowsiness alarms silenced. RESULTS: Twelve participants (3 female) completed all alcohol conditions. Relative to baseline, all eye blink parameters were affected at 0.08% BAC (all p < 0.05), whereas 0.05% BAC only affected the composite eye blink drowsiness measure (the Johns Drowsiness Scale). CONCLUSIONS: Alcohol consumption to 0.08% BAC impaired eye blink measures to a level that would be considered a moderate drowsiness risk. Therefore, employers should be aware that drowsiness alerts from these technologies may increase after alcohol consumption.

A brief assessment of eye blink drowsiness immediately prior to or following driving detects drowsiness related driving impairment.

Drowsy driving is a major cause of fatal and serious injury motor vehicle accidents. The inability objectively to assess drowsiness has hindered the assessment of fitness to drive and the development of drowsy driving regulations. This study evaluated whether spontaneous eye blink parameters measured briefly pre- and post-drive could be used to detect drowsy driving impairment. Twelve healthy participants (6 female) drove an instrumented vehicle for 2 h on a closed-loop track during a rested (8-10 h awake) and an extended wake condition (32-34 h awake). Pre- and post-drive, the participants completed a 5 min eye blink task, a psychomotor vigilance task (PVT), and the Karolinska sleepiness scale (KSS). Whole drive impairment was defined as >3.5 lane departures per hour. Severe end of drive impairment was defined as ≥2 lane departures in the last 15 min. The pre-drive % of time with eyes closed best predicted the whole drive impairment (area under the curve [AUC] 0.87). KSS had similar prediction ability (AUC 0.85), while PVT reaction time (AUC 0.72) was less accurate. The composite eye blink parameter, the Johns drowsiness scale was the best retrospective detector of severe end of drive impairment (AUC 0.99). The PVT reaction time (AUC 0.92) and the KSS (AUC 0.93) were less accurate. Eye blink parameters detected drowsy driving impairment with an accuracy that was similar to, or marginally better than, PVT and KSS. As eye blink measures are simple to measure, are objective and have high accuracy, they present an ideal option for the assessment of fitness for duty and roadside drowsiness.

Assessing the validity of eyelid parameters to detect impairment due to benzodiazepines.

OBJECTIVE: Benzodiazepines impair driving ability and psychomotor function. Eyelid parameters accurately reflect drowsiness; however, the effects of benzodiazepines on these measures have not been extensively studied. The aim of this study was to investigate the effect of benzodiazepines on eyelid parameters and evaluate their accuracy for detecting psychomotor impairment. METHODS: Eyelid parameters were recorded during a psychomotor vigilance task (PVT) and driving simulation over 2 days, baseline, and after 20-mg oral temazepam. The utility of eyelid parameters for detecting PVT lapses was evaluated using receiver operating characteristic curves, and cut-off levels indicating impairment (≥1 and ≥2 PVT lapses per min) were identified. The accuracy of these cut-off levels for detecting driving simulator crashes was then examined. RESULTS: PVT and driving simulator performance was significantly impaired following benzodiazepine administration (p < .05). Average eyelid closure duration (inter-event duration) was a reliable indicator of PVT lapses (area under the curve [AUC] of 0.87-0.90). The cut-off value of eyelid closure duration derived from PVT AUC was able to predict driving simulator crashes with moderately high sensitivity and specificity (76.23% and 75.00%). CONCLUSIONS: Eyelid parameters were affected by benzodiazepines and accurately detected the psychomotor impairment. In particular, eyelid closure duration is a promising real-time indicator of benzodiazepine impairment.

Eye-Blink Parameters Detect On-Road Track-Driving Impairment Following Severe Sleep Deprivation.

STUDY OBJECTIVES: Drowsiness leads to 20% of fatal road crashes, while inability to assess drowsiness has hampered drowsiness interventions. This study examined the accuracy of eye-blink parameters for detecting drowsiness related driving impairment in real time. METHODS: Twelve participants undertook two sessions of 2-hour track-driving in an instrumented vehicle following a normal night's sleep or 32 to 34 hours of extended wake in a randomized crossover design. Eye-blink parameters and lane excursion events were monitored continuously. RESULTS: Sleep deprivation increased the rates of out-of-lane driving events and early drive terminations. Episodes of prolonged eyelid closures, blink duration, the ratio of amplitude to velocity of eyelid closure, and John's Drowsiness Score (JDS, a composite score) were also increased following sleep deprivation. A time-on-task (drive duration) effect was evident for out-of-lane events rate and most eye-blink parameters after sleep deprivation. The JDS demonstrated the strongest association with the odds of out-of-lane events in the same minute, whereas measures of blink duration and prolonged eye closure were stronger indicators of risk for out-of-lane events over longer periods of 5 minutes and 15 minutes, respectively. Eye-blink parameters also achieved moderate accuracies (specificities from 70.12% to 84.15% at a sensitivity of 50%) for detecting out-of-lane events in the same minute, with stronger associations over longer timeframes of 5 minutes to 15 minutes. CONCLUSIONS: Eyelid closure parameters are useful tools for monitoring and predicting drowsiness-related driving impairment (out-of-lane events) that could be utilized for monitoring drowsiness and assessing the efficacy of drowsiness interventions. CLINICAL TRIAL REGISTRATION: This study is registered with the Australian New Zealand Clinical Trial Registry (ANCTR), http://www.anzctr.org.au/TrialSearch.aspx ACTRN12612000102875. CITATION: Shekari Soleimanloo S, Wilkinson VE, Cori JM,Westlake J, Stevens B, Downey LA, Shiferaw BA, Rajaratnam SMW, Howard ME. Eye-blink parameters detect on-road track-driving impairment following severe sleep deprivation. J Clin Sleep Med. 2019;15(9):1271-1284.

Apnoea and hypopnoea scoring for people with spinal cord injury: new thresholds for sleep disordered breathing diagnosis and severity classification.

STUDY DESIGN: Descriptive study. OBJECTIVES: To determine the effect of respiratory event rule-set changes on the apnoea hypopnoea index, and diagnostic and severity thresholds in people with acute and chronic spinal cord injury. SETTING: Eleven acute spinal cord injury inpatient hospitals across Australia, New Zealand, Canada and England; community dwelling chronic spinal cord injury patients in their own homes. METHODS: Polysomnography of people with acute (n = 24) and chronic (n = 78) tetraplegia were reanalysed from 1999 American Academy of Sleep Medicine (AASM) respiratory scoring, to 2007 AASM 'alternative' and 2012 AASM respectively. Equivalent cut points for published 1999 AASM sleep disordered breathing severity ranges were calculated using receiver operator curves, and results presented alongside analyses from the able-bodied. RESULTS: In people with tetraplegia, shift from 1999 AASM to 2007 AASM 'alternative' resulted in a 22% lower apnoea hypopnoea index, and to 2012 AASM a 17% lower index. In people with tetraplegia, equivalent cut-points for 1999 AASM severities of 5,15 and 30 were calculated at 2.4, 8.1 and 16.3 for 2007 AASM 'alternative' and 3.2, 10.0 and 21.2 for 2012 AASM. CONCLUSION: Interpreting research, prevalence and clinical polysomnography results conducted over different periods requires knowledge of the relationship between different rule-sets, and appropriate thresholds for diagnosis of disease. SPONSORSHIP: This project was proudly supported by the Traffic Accident Commission (Program grant) and the National Health and Medical Research Council (PhD stipend 616605).

Worth the effort? Weighing up the benefit and burden of continuous positive airway pressure therapy for the treatment of obstructive sleep apnoea in chronic tetraplegia.

STUDY DESIGN: Mixed methods OBJECTIVES: Continuous positive airway pressure (CPAP) therapy is the recommended treatment for obstructive sleep apnoea (OSA). The aim of this study was to estimate CPAP adherence in people with tetraplegia and OSA, and to explore the barriers and facilitators to CPAP use. SETTING: Hospital outpatient department in Melbourne, Australia METHODS: People with chronic tetraplegia and OSA were commenced with auto-titrating CPAP and supported for 1 month. Semi-structured interviews were conducted with participants at one month and analysed thematically. CPAP usage was measured at 1, 6 and 12 months, with "adherent" defined as achieving more than 4 h average per night. RESULTS: Sixteen participants completed the study (80% male; mean age 56 (SD = 15)). Mean nightly CPAP use at one month was 3.1 h (SD = 2.5; 38% adherent), and at 6 months and 12 months were 2.6 h (SD = 2.8; 25% adherent) and 2.1 h (SD = 3.2; 25% adherent). The perceived benefit/burden balance strongly influenced ongoing use. Burden attributed to CPAP use was common, and included mask discomfort, and physical and emotional problems. Adherent participants were motivated by the immediate daytime benefits to mood, alertness and sleepiness. There was a tendency to not recognise symptoms of OSA until after they were treated. CONCLUSION: CPAP use is challenging for people with tetraplegia, who experience substantial burden from using the device. When tolerated, the proximate benefits are substantial. People with tetraplegia need more intensive support for longer to help them overcome the burdens of CPAP and benefit from the treatment.

Stationary gaze entropy predicts lane departure events in sleep-deprived drivers.

Performance decrement associated with sleep deprivation is a leading contributor to traffic accidents and fatalities. While current research has focused on eye blink parameters as physiological indicators of driver drowsiness, little is understood of how gaze behaviour alters as a result of sleep deprivation. In particular, the effect of sleep deprivation on gaze entropy has not been previously examined. In this randomised, repeated measures study, 9 (4 male, 5 female) healthy participants completed two driving sessions in a fully instrumented vehicle (1 after a night of sleep deprivation and 1 after normal sleep) on a closed track, during which eye movement activity and lane departure events were recorded. Following sleep deprivation, the rate of fixations reduced while blink rate and duration as well as saccade amplitude increased. In addition, stationary and transition entropy of gaze also increased following sleep deprivation as well as with amount of time driven. An increase in stationary gaze entropy in particular was associated with higher odds of a lane departure event occurrence. These results highlight how fatigue induced by sleep deprivation and time-on-task effects can impair drivers' visual awareness through disruption of gaze distribution and scanning patterns.

A randomised controlled trial of CPAP versus non-invasive ventilation for initial treatment of obesity hypoventilation syndrome.

BACKGROUND: Obesity hypoventilation syndrome (OHS) is the most common indication for home ventilation, although the optimal therapy remains unclear, particularly for severe disease. We compared Bi-level and continuous positive airways pressure (Bi-level positive airway pressure (PAP); CPAP) for treatment of severe OHS. METHODS: We conducted a multicentre, parallel, double-blind trial for initial treatment of OHS, with participants randomised to nocturnal Bi-level PAP or CPAP for 3 months. The primary outcome was frequency of treatment failure (hospital admission, persistent ventilatory failure or non-adherence); secondary outcomes included health-related quality of life (HRQoL) and sleepiness. RESULTS: Sixty participants were randomised; 57 completed follow-up and were included in analysis (mean age 53 years, body mass index 55 kg/m2, PaCO2 60 mm Hg). There was no difference in treatment failure between groups (Bi-level PAP, 14.8% vs CPAP, 13.3%, p=0.87). Treatment adherence and wake PaCO2 were similar after 3 months (5.3 hours/night Bi-level PAP, 5.0 hours/night CPAP, p=0.62; PaCO2 44.2 and 45.9 mm Hg, respectively, p=0.60). Between-group differences in improvement in sleepiness (Epworth Sleepiness Scale 0.3 (95% CI -2.8, 3.4), p=0.86) and HRQoL (Short Form (SF)36-SF6d 0.025 (95% CI -0.039, 0.088), p=0.45) were not significant. Baseline severity of ventilatory failure (PaCO2) was the only significant predictor of persistent ventilatory failure at 3 months (OR 2.3, p=0.03). CONCLUSIONS: In newly diagnosed severe OHS, Bi-level PAP and CPAP resulted in similar improvements in ventilatory failure, HRQoL and adherence. Baseline PaCO2 predicted persistent ventilatory failure on treatment. Long-term studies are required to determine whether these treatments have different cost-effectiveness or impact on mortality. TRIAL REGISTRATION NUMBER: ACTRN12611000874910, results.

The effects of direct and indirect road transport consignment in combination with feed withdrawal in young dairy calves.

Male dairy calves may be transported from their farm of origin at a young age. This process may involve an extended period off feed and indirect consignment through an intermediate facility, prompting potential welfare concerns. To assess the impact of transport, 59 male Holstein-Friesian dairy calves (5-9 d old) were either (1) held in situ on farm (control); (2) transported for 6 h; (3) transported for 12 h; or (4) transported for 1 h to a holding facility where they were kept for 6 h and then transported for 5 h. All treatments included a 30-h period of feed (milk) withdrawal, and calf responses were measured over time from before their last feed until the completion of the study after the transport and feed withdrawal periods. Apart from increases in serum creatine kinase in calves transported for 12 h, transported calves generally did not differ in blood concentrations of glucose, beta-hydroxybutyrate, lactate, total protein or in packed cell volume, compared with controls (P>0.05). Calf responses to the indirect consignment treatment did not differ from those of other transported calves. Withdrawal of feed for 30 h caused calves to lose 6% of body weight; blood glucose varied from 3.96 mmol/l immediately before daily feeding to 5.46 mmol/l at 3 h post feeding, and then declined to 3.43 mmol/l at 30 h. Calves lay down for 22-32% of the time during transport, and did not show a rebound effect in lying behaviour post arrival in comparison with controls. Best practice transport of 6-12 h duration, including indirect consignment via a holding facility, did not significantly affect calf blood biochemistry and metabolism in comparison with untransported animals. However, extending the time off feed beyond the daily feeding interval resulted in reduced blood glucose concentrations, suggesting that time off feed needs to be carefully managed in young transported dairy calves.

The accuracy of eyelid movement parameters for drowsiness detection.

STUDY OBJECTIVES: Drowsiness is a major risk factor for motor vehicle and occupational accidents. Real-time objective indicators of drowsiness could potentially identify drowsy individuals with the goal of intervening before an accident occurs. Several ocular measures are promising objective indicators of drowsiness; however, there is a lack of studies evaluating their accuracy for detecting behavioral impairment due to drowsiness in real time. METHODS: In this study, eye movement parameters were measured during vigilance tasks following restricted sleep and in a rested state (n = 33 participants) at three testing points (n = 71 data points) to compare ocular measures to a gold standard measure of drowsiness (OSLER). The utility of these parameters for detecting drowsiness-related errors was evaluated using receiver operating characteristic curves (ROC) (adjusted by clustering for participant) and identification of optimal cutoff levels for identifying frequent drowsiness-related errors (4 missed signals in a minute using OSLER). Their accuracy was tested for detecting increasing frequencies of behavioral lapses on a different task (psychomotor vigilance task [PVT]). RESULTS: Ocular variables which measured the average duration of eyelid closure (inter-event duration [IED]) and the ratio of the amplitude to velocity of eyelid closure were reliable indicators of frequent errors (area under the curve for ROC of 0.73 to 0.83, p < 0.05). IED produced a sensitivity and specificity of 71% and 88% for detecting ≥ 3 lapses (PVT) in a minute and 100% and 86% for ≥ 5 lapses. A composite measure of several eye movement characteristics (Johns Drowsiness Scale) provided sensitivities of 77% and 100% for detecting 3 and ≥ 5 lapses in a minute, with specificities of 85% and 83%, respectively. CONCLUSIONS: Ocular measures, particularly those measuring the average duration of episodes of eye closure are promising real-time indicators of drowsiness.

The 2007 AASM recommendations for EEG electrode placement in polysomnography: impact on sleep and cortical arousal scoring.

STUDY OBJECTIVE: To examine the impact of using American Academy of Sleep Medicine (AASM) recommended EEG derivations (F4/M1, C4/M1, O2/M1) vs. a single derivation (C4/M1) in polysomnography (PSG) on the measurement of sleep and cortical arousals, including inter- and intra-observer variability. DESIGN: Prospective, non-blinded, randomized comparison. SETTING: Three Australian tertiary-care hospital clinical sleep laboratories. PATIENTS OR PARTICIPANTS: 30 PSGs from consecutive patients investigated for obstructive sleep apnea (OSA) during December 2007 and January 2008. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: To examine the impact of EEG derivations on PSG summary statistics, 3 scorers from different Australian clinical sleep laboratories each scored separate sets of 10 PSGs twice, once using 3 EEG derivations and once using 1 EEG derivation. To examine the impact on inter- and intra-scorer reliability, all 3 scorers scored a subset of 10 PSGs 4 times, twice using each method. All PSGs were de-identified and scored in random order according to the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Using 3 referential EEG derivations during PSG, as recommended in the AASM manual, instead of a single central EEG derivation, as originally suggested by Rechtschaffen and Kales (1968), resulted in a mean ± SE decrease in N1 sleep of 9.6 ± 3.9 min (P = 0.018) and an increase in N3 sleep of 10.6 ± 2.8 min (P = 0.001). No significant differences were observed for any other sleep or arousal scoring summary statistics; nor were any differences observed in inter-scorer or intra-scorer reliability for scoring sleep or cortical arousals. CONCLUSION: This study provides information for those changing practice to comply with the 2007 AASM recommendations for EEG placement in PSG, for those using portable devices that are unable to comply with the recommendations due to limited channel options, and for the development of future standards for PSG scoring and recording. As the use of multiple EEG derivations only led to small changes in the distribution of derived sleep stages and no significant differences in scoring reliability, this study calls into question the need to use multiple EEG derivations in clinical PSG as suggested in the AASM manual.