Understanding Brain Cleaning in Obstructive Sleep Apnoea

Obstructive Sleep Apnoea (OSA) is a common condition characterised frequent collapsing of the airway during sleep, causing fragmented sleep and intermittent hypoxia. OSA has recently been identified as a risk factor for dementia, however the pathophysiological mechanisms remain unclear. Research in the past decade has identified a key role of good quality sleep in the removal of toxic brain metabolites (such as beta amyloid) that underpin dementia. Studies in mice and humans have clearly identified a sleep-wake rhythm in the cerebrospinal fluid concentration of these metabolites. This rhythm is characterised by a rise in concentration during wakefulness and a fall during sleep. Recently it has become possible to detect these metabolites in blood, making it easier to understand the pathophysiological mechanisms that inhibit brain detoxification during sleep.We propose a 3-year study to explore, across the sleep-wake cycle, the blood concentration profiles of brain-derived metabolites that underpin dementia in people with OSA. We will use an OSA treatment withdrawal study design to fragment sleep and increase blood pressure disturbances to understand their impact on inhibiting the brain cleaning process. Our multidisciplinary team of CIs & AIs have skills in neurophysiology, sleep, circadian and systems modelling, sleep physiology, cardiovascular physiology, MRI/MRS assessments, data science, sleep medicine and dementia biomarkers. We have full access to state-of-the-art facilities, all equipment and assays required to successfully complete this research.