Mark Howard

Cognition and daytime functioning in sleep-related breathing disorders

Sleep-related breathing disorders encompass a range of disorders in which abnormal ventilation occurs during sleep as a result of partial or complete obstruction of the upper airway, altered respiratory drive, abnormal chest wall movement, or respiratory muscle function. The most common of these is obstructive sleep apnea (OSA), occurring in both adults and children, and causing significant cognitive and daytime dysfunction and reduced quality of life. OSA patients experience repetitive brief cessation of breathing throughout the night, which causes intermittent hypoxemia (reductions in hemoglobin oxygen levels) and fragmented sleep patterns. These nocturnal events result in excessive daytime sleepiness, and changes in mood and cognition. Chronic excessive sleepiness during the day is a common symptom of sleep-related breathing disorders, which is assessed in sleep clinics both subjectively (questionnaire) and objectively (sleep latency tests). Mood changes are often reported by patients, including irritability, fatigue, depression, and anxiety. A wide range of cognitive deficits have been identified in untreated OSA patients, from attentional and vigilance, to memory and executive functions, and more complex tasks such as simulated driving. These changes are reflected in patient reports of difficulty in concentrating, increased forgetfulness, an inability to make decisions, and falling asleep at the wheel of a motor vehicle. These cognitive changes can also have significant downstream effects on daily functioning. Moderate to severe cases of the disorder are at a higher risk of having a motor vehicle accident, and may also have difficulties at work or school. A number of comorbidities may also influence the cognitive changes in OSA patients, including hypertension, diabetes, and stroke. These diseases can cause changes to neural vasculature and result in neural damage, leading to cognitive impairments. Examination of OSA patients using neuroimaging techniques such as structural magnetic resonance imaging and proton magnetic resonance spectroscopy has observed significant changes to brain structure and metabolism. The downstream effects of neural, cognitive, and daytime functional impairments can be significant if left untreated. A better understanding of the cognitive effects of these disorders, and development of more effective assessment tools for diagnosis, will aid early intervention and improve quality of life of the patient.

Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment

STUDY OBJECTIVES To determine whether cerebral metabolite changes may underlie abnormalities of neurocognitive function and respiratory control in OSA. DESIGN Observational, before and after CPAP treatment. SETTING Two tertiary hospital research institutes. PARTICIPANTS 30 untreated severe OSA patients, and 25 age-matched healthy controls, all males free of comorbidities, and all having had detailed structural brain analysis using voxel-based morphometry (VBM). MEASUREMENTS AND RESULTS Single voxel bilateral hippocampal and brainstem, and multivoxel frontal metabolite concentrations were measured using magnetic resonance spectroscopy (MRS) in a high resolution (3T) scanner. Subjects also completed a battery of neurocognitive tests. Patients had repeat testing after 6 months of CPAP. There were significant differences at baseline in frontal N-acetylaspartate/choline (NAA/Cho) ratios (patients [mean (SD)] 4.56 [0.41], controls 4.92 [0.44], P = 0.001), and in hippocampal choline/creatine (Cho/Cr) ratios (0.38 [0.04] vs 0.41 [0.04], P = 0.006), (both ANCOVA, with age and premorbid IQ as covariates). No longitudinal changes were seen with treatment (n = 27, paired t tests), however the hippocampal differences were no longer significant at 6 months, and frontal NAA/Cr ratios were now also significantly different (patients 1.55 [0.13] vs control 1.65 [0.18] P = 0.01). No significant correlations were found between spectroscopy results and neurocognitive test results, but significant negative correlations were seen between arousal index and frontal NAA/Cho (r = -0.39, corrected P = 0.033) and between % total sleep time at SpO(2) < 90% and hippocampal Cho/Cr (r = -0.40, corrected P = 0.01). CONCLUSIONS OSA patients have brain metabolite changes detected by MRS, suggestive of decreased frontal lobe neuronal viability and integrity, and decreased hippocampal membrane turnover. These regions have previously been shown to have no gross structural lesions using VBM. Little change was seen with treatment with CPAP for 6 months. No correlation of metabolite concentrations was seen with results on neurocognitive tests, but there were significant negative correlations with OSA severity as measured by severity of nocturnal hypoxemia.

Cognitive components of simulated driving performance: Sleep loss effects and predictors

Driving is a complex task, which can be broken down into specific cognitive processes. In order to determine which components contribute to drowsy driving impairments, the current study examined simulated driving and neurocognitive performance after one night of sleep deprivation. Nineteen professional drivers (age 45.3±9.1) underwent two experimental sessions in randomised order: one after normal sleep and one after 27h total sleep deprivation. A simulated driving task (AusEd), the psychomotor vigilance test (PVT), and neurocognitive tasks selected from the Cognitive Drug Research computerised neurocognitive assessment battery (simple and choice RT, Stroop Task, Digit Symbol Substitution Task, and Digit Vigilance Task) were administered at 10:00h in both sessions. Mixed-effects ANOVAs were performed to examine the effect of sleep deprivation versus normal sleep on performance measures. To determine if any neurocognitive tests predicted driving performance (lane position variability, speed variability, braking RT), neurocognitive measures that were significantly affected by sleep deprivation were then added as a covariate to the ANOVAs for driving performance. Simulated driving performance and neurocognitive measures of vigilance and reaction time were impaired after sleep deprivation (p<0.05), whereas tasks examining processing speed and executive functioning were not significantly affected by sleep loss. PVT performance significantly predicted specific aspects of simulated driving performance. Thus, psychomotor vigilance impairment may be a key cognitive component of driving impairment when sleep deprived. The generalisability of this finding to real-world driving remains to be investigated.

Sleep loss and circadian disruption in shift work: health burden and management.

Road and workplace accidents related to excessive sleepiness, to which shift work is a significant contributor, are estimated to cost

Objective and subjective measures of sleepiness, and their associations with on-road driving events in shift workers

71–

Effects of Maternal Obstructive Sleep Apnoea on Fetal Growth: A Prospective Cohort Study

93 billion per annum in the United States. There is growing evidence that understanding the interindividual variability in sleep–wake responses to shift work will help detect and manage workers vulnerable to the health consequences of shift work. A range of approaches can be used to enhance alertness in shift workers, including screening and treating sleep disorders, melatonin treatment to promote sleep during the daytime, and avoidance of inappropriate use of sedatives and wakefulness‐promoters such as modafinil and caffeine. Short naps, which minimise sleep inertia, are generally effective. Shifting the circadian pacemaker with appropriately timed melatonin and/or bright light may be used to facilitate adjustment to a shift work schedule in some situations, such as a long sequence of night work. It is important to manage the health risk of shift workers by minimising vascular risk factors through dietary and other lifestyle approaches.

Home mechanical ventilation in australia and new zealand

To assess the relationships between sleepiness and the incidence of adverse driving events in nurses commuting to and from night and rotating shifts, 27 rotating and permanent night shift‐working nurses were asked to complete daily sleep and duty logs, and wear wrist‐activity monitors for 2 weeks (369 driving sessions). During all commutes, ocular measures of drowsiness, including the Johns Drowsiness Scale score, were assessed using the Optalert™ system. Participants self‐reported their subjective sleepiness at the beginning and end of each drive, and any events that occurred during the drive. Rotating shift nurses reported higher levels of sleepiness compared with permanent night shift nurses. In both shift‐working groups, self‐reported sleepiness, drowsiness and drive events were significantly higher during commutes following night shifts compared with commutes before night shifts. Strong associations were found between objective drowsiness and increased odds of driving events during commutes following night shifts. Maximum total blink duration (mean = 7.96 s) during the drive and pre‐drive Karolinska Sleepiness Scale (mean = 5.0) were associated with greater incidence of sleep‐related events [OR, 5.35 (95% CI, 1.32, 21.60), OR, 1.69 (95% CI, 1.04, 2.73), respectively]. Inattention was strongly associated with a Johns Drowsiness Scale score equal to or above 4.5 [OR, 4.58 (95% CI, 1.26–16.69)]. Hazardous driving events were more likely to occur when drivers had been awake for 16 h or more [OR, 4.50 (95% CI, 1.81, 11.16)]. Under real‐world driving conditions, shift‐working nurses experience high levels of drowsiness as indicated by ocular measures, which are associated with impaired driving performance following night shift work.

A comparison of the effect of mobile phone use and alcohol consumption on driving simulation performance

Objective The objective of this study is to determine whether obstructive sleep apnea (OSA) is associated with reduced fetal growth, and whether nocturnal oxygen desaturation precipitates acute fetal heart rate changes. Study Design We performed a prospective observational study, screening 371 women in the second trimester for OSA symptoms. 41 subsequently underwent overnight sleep studies to diagnose OSA. Third trimester fetal growth was assessed using ultrasound. Fetal heart rate monitoring accompanied the sleep study. Cord blood was taken at delivery, to measure key regulators of fetal growth. Results Of 371 women screened, 108 (29%) were high risk for OSA. 26 high risk and 15 low risk women completed the longitudinal study; 14 had confirmed OSA (cases), and 27 were controls. The median (interquartile range) respiratory disturbance index (number of apnoeas, hypopnoeas or respiratory related arousals/hour of sleep) was 7.9 (6.1–13.8) for cases and 2.2 (1.3–3.5) for controls (p<0.001). Impaired fetal growth was observed in 43% (6/14) of cases, vs 11% (3/27) of controls (RR 2.67; 1.25–5.7; p = 0.04). Using logistic regression, only OSA (OR 6; 1.2–29.7, p = 0.03) and body mass index (OR 2.52; 1.09–5.80, p = 0.03) were significantly associated with impaired fetal growth. After adjusting for body mass index on multivariate analysis, the association between OSA and impaired fetal growth was not appreciably altered (OR 5.3; 0.93–30.34, p = 0.06), although just failed to achieve statistical significance. Prolonged fetal heart rate decelerations accompanied nocturnal oxygen desaturation in one fetus, subsequently found to be severely growth restricted. Fetal growth regulators showed changes in the expected direction- with IGF-1 lower, and IGFBP-1 and IGFBP-2 higher- in the cord blood of infants of cases vs controls, although were not significantly different. Conclusion OSA may be associated with reduced fetal growth in late pregnancy. Further evaluation is warranted to establish whether OSA may be an important contributor to adverse perinatal outcome, including stillbirth.

Pulmonary presentations of amyloidosis

This study aims to describe the pattern of home mechanical ventilation (HMV) usage in Australia and New Zealand. 34 centres providing HMV in the region were identified and asked to complete a questionnaire regarding centre demographics, patient diagnoses, HMV equipment and settings, staffing levels and methods employed to implement and follow-up therapy. 28 (82%) centres responded, providing data on 2,725 patients. The minimum prevalence of HMV usage was 9.9 patients per 100,000 population in Australia and 12.0 patients per 100,000 population in New Zealand. Variation existed across Australian states (range 4–13 patients per 100,000 population) correlating with population density (r=0.82; p<0.05). The commonest indications for treatment were obesity hypoventilation syndrome (OHS) (31%) and neuromuscular disease (NMD) (30%). OHS was more likely to be treated in New Zealand, in smaller, newer centres, whilst NMD was more likely to be treated in Australia, in larger, older centres. Chronic obstructive pulmonary disease was an uncommon indication (8.0%). No consensus on indications for commencing treatment was found. In conclusion, the prevalence of HMV usage varies across Australia and New Zealand according to centre location, size and experience. These findings can assist HMV service planning locally and highlight trends in usage that may be relevant in other countries.

High risk of near-crash driving events following night-shift work

Objective: The present study compared the effects of a variety of mobile phone usage conditions to different levels of alcohol intoxication on simulated driving performance and psychomotor vigilance. Methods: Twelve healthy volunteers participated in a crossover design in which each participant completed a simulated driving task on 2 days, separated by a 1-week washout period. On the mobile phone day, participants performed the simulated driving task under each of 4 conditions: no phone usage, a hands-free naturalistic conversation, a hands-free cognitively demanding conversation, and texting. On the alcohol day, participants performed the simulated driving task at four different blood alcohol concentration (BAC) levels: 0.00, 0.04, 0.07, and 0.10. Driving performance was assessed by variables including time within target speed range, time spent speeding, braking reaction time, speed deviation, and lateral lane position deviation. Results: In the BAC 0.07 and 0.10 alcohol conditions, participants spent less time in the target speed range and more time speeding and took longer to brake in the BAC 0.04, 0.07, and 0.10 than in the BAC 0.00 condition. In the mobile phone condition, participants took longer to brake in the natural hands-free conversation, cognitively demanding hands-free conversation and texting conditions and spent less time in the target speed range and more time speeding in the cognitively demanding, hands-free conversation, and texting conditions. When comparing the 2 conditions, the naturalistic conversation was comparable to the legally permissible BAC level (0.04), and the cognitively demanding and texting conversations were similar to the BAC 0.07 to 0.10 results. Conclusion: The findings of the current laboratory study suggest that very simple conversations on a mobile phone may not represent a significant driving risk (compared to legally permissible BAC levels), whereas cognitively demanding, hands-free conversation, and particularly texting represent significant risks to driving.