Neurocognitive disturbance in obstructive sleep apnoea: mechanisms of harm

The overarching aim addressed by this thesis was the investigation of the relationship between cognitive dysfunction and mechanisms of harm (sleep fragmentation and hypoxia) in Obstructive Sleep Apnoea (OSA). It begins with a general introduction to the nocturnal features and cognitive profile of OSA (Chapter 1), continues with three research studies (reported over Chapters 2, 4 and 5, Chapter 3 details methods and recruitment), and concludes with a general discussion (Chapter 6). Study 1 (Chapter 2) considered the profile of executive dysfunction in individuals with OSA. OSA is a frequent and often under-diagnosed condition that is associated with upper airway collapse, oxygen desaturation, and sleep fragmentation leading to cognitive dysfunction. There is good meta-analytic evidence that subdomains of attention and memory are affected by OSA. However, a thorough investigation of the impact of OSA on different sub-domains of executive function had yet to be conducted. Study 1 (Chapter 2) investigated the impact of untreated and treated OSA, in adult patients, on five, theorised, sub-domains of executive function. An extensive literature search was conducted of published and unpublished materials, returning 35 studies that matched selection criteria. Meta-analysis was used to synthesise the results from studies examining the impact of OSA on executive functioning compared to controls (21 studies) and before and after treatment (19 studies); 5 studies met inclusion in both categories. All domains of executive function (Shifting, Updating, Inhibition, Generativity and Fluid Reasoning) demonstrated medium to very large impairments in OSA independent of age, and disease severity. All domains improved (small to medium effects) with CPAP treatment, and this Neurocognitive Disturbance in OSA iii improvement was not moderated by age or disease severity. Further studies are needed to explore the extent of primary (neural damage in a region, with corresponding behavioural dysfunction, e.g., damage to areas responsible for memory, and demonstrated memory difficulties) or secondary nature (neural damage resulting in secondary dysfunction, e.g., damage in areas responsible for attention control, impacting on memory capacity) of these deficits, and the impact of age and pre-morbid ability (cognitive reserve). Chapter 3 reports the recruitment procedures, participants and methods used in this thesis. Study 2 (Chapter 4) assessed the measurement of sleepiness using the Epworth Sleepiness Scale (ESS) prior to inclusion of this construct as a covariate in Study 3. The ESS is a widely used tool for measuring sleepiness. In addition to providing a single measure of sleepiness (a one factor structure), the ESS also has the capacity to provide additional information about specific factors that facilitate sleep-onset, including a person’s posture, activity and environment. These features of sleepiness are referred to as somnificity. Study 2 (Chapter 3) evaluated the fit of a 1-factor structure (sleepiness) and a 3-factor structure (reflecting low, medium and high levels of somnificity) for the ESS using Confirmatory Factor Analysis (CFA). Two samples (a community sample N = 356 and a clinical sample N = 679) were administered the ESS. In both samples, a 3-factor structure (community sample adjusted X2 = 2.95, RMSEA = .07, CFI = .95; clinical sample adjusted X2 = 3.98, RMSEA = .07, CFI = .98) provided a level of model fit that was at least as good as the 1-factor structure (community sample adjusted X2 = 5.01, RMSEA = .11, CFI = .87; clinical sample adjusted X2 = 8.87, RMSEA = .11, CFI = .92). In addition to a single measure of Neurocognitive Disturbance in OSA iv sleepiness, the ESS can provide subscale scores that relate to three underlying levels of somnificity. These findings suggest that the ESS can be used to measure an individual’s overall sleep propensity as well as more specific measures of sleep propensity in low, moderate and high levels of situational somnificity. Due to the findings of this chapter, the ESS was included as a covariate in Study 3, run in the model as a single factor, and as three factors to evaluate model fit. Study 3 (Chapters 5) determined the influence of hypoxia and sleep fragmentation on cognition in OSA, while controlling for potentially confounding variables including subjective sleepiness (using results from Study 2), age and premorbid intelligence. Participants with and without OSA (N = 150) were recruited from the general community and a tertiary hospital sleep clinic. All underwent comprehensive, laboratory-based polysomnography and completed assessments of cognition including attention, short-term & long-term memory and executive function. Structural Equation Modelling (SEM) was used to construct a theoretically driven model to examine the relationships between hypoxia and sleep fragmentation, and cognitive function. Increased sleep disturbance was a significant predictor of decreased attention (p = .04) and decreased executive function (p = .05), after controlling for IQ. No significant predictors of memory function were found, and hypoxia was not related to any cognitive domain. Controlling for age removes the significant relationships between sleep fragmentation, attention and executive