Factors associated with cognitive impairment in obstructive sleep apnoea
Creators: name: ALOMRI, Ridwan
Publisher: name: RMIT University
Year: 2024
Subjects: classificationCode: 520203
subject: Cognitive neuroscience

description: Obstructive sleep apnoea (OSA) is a sleep disorder characterised by repetitive episodes of airway obstruction, which lead to transient hypoxia and sleep fragmentation. Persons with OSA can suffer from excessive daytime sleepiness (EDS) and mood swings and are twice as likely as healthy peers to have difficulty concentrating, performing repetitive tasks and acquiring new knowledge. Sleep fragmentation and intermittent hypoxia (IH) are only able to account for 30-40% of the cognitive impairment, so additional factors must be involved. One possibility is depressive symptoms, as these are common in OSA. People with depressive symptoms but no other comorbid condition exhibit cognitive deficits that can include memory loss, ambiguity in decision making, a decline in judgment and problem-solving skills and an inability to pay attention during routine activities. Another potential factor is increased nocturnal activity of the sympathetic nervous system (SNS), which can lead to changes in heartbeat and spikes in nocturnal blood pressure (BP). In the general population, high BP in midlife has been strongly linked to impairments in visuospatial ability, motor speed and attention. Since little is known about the contributions of depressive symptoms and SNS over-activation to the cognitive impairments in OSA, the present study has examined whether these factors are associated with cognitive impairments in OSA patients, after controlling for the confounding effects of age, smoking, IH and sleep fragmentation.

The first aim of this study was to characterise the participants. They were drawn from patients who had been referred to a Saudi Arabian sleep laboratory to undergo a sleep study using polysomnography (PSG). It was hypothesised that participants should show no differences in OSA characteristics or risk factors compared with participants in previous studies in Western countries. Of the 100 patients who presented consecutively to the Sleep Medicine and Research Centre, 90 met the study inclusion criteria. This study measured OSA via overnight PSG and the participants were asked to complete the Arabic version of the STOP-Bang questionnaire (SBQ). Of the participants, 62 (69%) were male; mean participant age was 42.0 ± 12.7 years; and mean Body Mass Index (BMI) was 33.4 ± 9.4 kg/m2. PSG showed that 14 of the 90 participants did not have OSA, 30 had mild OSA, 23 had moderate OSA and 23 had severe OSA. Eight of the 90 participants did not answer the SBQ completely; therefore, the SBQ data are from 82 participants. Multiple regression analysis revealed that age and BMI (p &lt; .05) but not smoking status (p &gt; .05) were significant predictors of OSA severity. The prevalence of depressive symptoms and EDS was 74% and 50%, respectively. In addition, 60% of participants with OSA had impaired glucose tolerance (IGT) or type 2 diabetes (T2D). These proportions are similar to reports from other countries, making it likely that the research findings from this Saudi cohort have global relevance.

Data from this cohort demonstrated a significant correlation (p &lt; .05) between the SBQ score and the Apnoea¿Hypopnea Index (AHI), confirming the utility of the SBQ as a predictor of OSA severity. Receiver operating characteristic curve analysis revealed that a total SBQ score &gt;2 predicted an AHI &gt; 5 with high sensitivity (90%) but low specificity (54%), and an AHI of &gt;15 with a sensitivity of 98% and a specificity of 32%. The loud snoring item provided superior prediction of mild OSA (AHI &gt;5), while the observed apnoeas item predicted an AHI &gt;15 with a sensitivity of 87% and specificity of 76%.

The second aim was to determine the extent to which IH, sleep fragmentation and depression are independently associated with cognitive impairment. Hypoxia was measured as time spent with a blood oxygen concentration of &lt;90% during sleep, and sleep fragmentation was measured using the Arousal Index. Depressive symptoms were determined by the depression subscale of the Depression-Anxiety Stress Scale (DASS-21). Cognitive function was evaluated using the 10-trial Austin maze (visuospatial ability), the 10-minute psychomotor vigilance test (sustained attention and reaction time [RT]) and the Autobiographical Memory Interview (semantic and episodic memories). IH was independently associated with impairments in sustained attention and RT (p &lt; .05). Sleep fragmentation was independently related to impairments in visuospatial ability (p &lt; .05). Depressive symptoms were independently associated with impairments in the domains of sustained attention, RT, visuospatial ability and semantic and episodic memories (p &lt; .05).

The third aim was to investigate the contributions of SNS over-activity to cognitive impairment. It was hypothesised that SNS over-activity might be a significant contributor to cognitive impairment in OSA patients. SNS activity was measured using heart rate variability (HRV; high-to-low frequency ratio), pulse wave amplitude (PWA) drops and stress response biomarkers (first-morning sample of urinary and blood cortisol, and blood glucose). PWA, HRV and morning blood glucose (p &lt; .005), but not morning urine and blood cortisol, were associated with OSA severity. Moreover, the PWA index, PWA time duration and HRV ratio were associated with impaired visuospatial ability (p &lt; .005). However, impairments in sustained attention, RT and autobiographical memory were not significantly associated with any of the SNS indices.

The fourth aim was to investigate whether nocturnal peaks in BP are associated with cognitive dysfunction in patients with clinically verified OSA. It was hypothesised that as high BP is known to damage the cerebral cortex through micro-strokes, peaks of nocturnal BP might be associated with impaired cognitive function. Nocturnal peaks in BP were measured continuously (beat-to-beat) using the pulse transit time method. Results showed that nocturnal peaks in systolic blood pressure (SBP) were associated with OSA severity (p &lt; .005), whereas diastolic BP peaks were not. Moreover, patients with the most severe OSA had the largest differences between resting and nocturnal SBP (p &lt; .005). Additionally, peaks in nocturnal SBP and the mean value of the differences between resting and nocturnal SBP were associated with impaired visuospatial ability (p &lt; .005). Impairments in sustained attention and RT, and autobiographical memory were not significantly associated with nocturnal BP.
This study has shown that IH, sleep fragmentation and depressive symptoms independently contribute to cognitive impairment in OSA. Further, PWA, HRV and nocturnal peaks in SBP correlate with impairments in visuospatial function. The present study has extended understanding of the factors that contribute to cognitive impairment in OSA by revealing that two additional factors, depressive symptoms and SNS over-activation, appear to account for some of the cognitive impairment, independently of age, smoking, nocturnal hypoxia and arousals from sleep. These novel findings have implications for both the measurement of OSA in overnight sleep studies and for the treatment of cognitive impairment in patients with OSA.