Exploring the role of slow wave sleep as a target for glymphatic clearance and associated development of Alzheimer’s disease.

Many older adults experience some form of cognitive decline. However, for one in ten adults, cognition will decline relentlessly to warrant a clinical diagnosis of dementia. Alzheimer’s disease is the most common form of dementia, comprising 60-80% of all cases.

Despite no cure for the disease, a large proportion of Alzheimer’s disease risk is modifiable. Many research efforts are now focussing on early diagnostic preclinical biomarkers and modifiable risk factors to delay or offset diagnosis. Evidence is rapidly emerging highlighting the potential role of sleep as modifiable target to offset the risk of Alzheimer’s disease.

Slow wave sleep, the deepest stage of non-REM sleep, plays an essential role in the maintenance of brain health and cognitive function across the lifespan. With age, reductions in slow wave sleep occurs across all adults, and this is accelerated for those with preclinical or diagnosed Alzheimer’s disease. As slow wave sleep plays a crucial role in the consolidation of memory and the clearing of waste products in the brain, it serves as a primary target for sleep-related Alzheimer’s disease risk. Accumulation of beta-Amyloid is central to the development of Alzheimer’s disease, and animal models suggest that beta-Amyloid clearance via the glymphatic system is dependent on the neuronal pulsing of slow wave sleep.

There exists an exciting opportunity to explore these associations in human participants to provide crucial evidence that (slow wave) sleep is an important target to offset Alzheimer’s disease risk. This PhD will provide foundational data to understand further the link between brain state during slow wave sleep and the pathogenesis of Alzheimer’s disease with particular focus on the clearance of beta-Amyloid and other related blood-based markers.

First, EEG-based markers of brain state during slow wave sleep (beyond traditional power spectra approaches) will be examined across a range of older adults (50-80 years) presenting to a research memory clinic for assessment and clinically identified as prodromal, preclinical or existing Alzheimer’s disease. The association between these novel EEG markers and established markers of the disease (cognition, blood-based biomarkers) will be explored. Second, the association between novel EEG-based markers and neural/biological indicators of glymphatic clearance will be explored in a highly controlled multi-modal laboratory-based study. Finally, night-to-night stability of these associations will be examined to ensure the robustness of any future target.

This PhD project provides an opportunity to work in a cutting-edge environment, with a transdisciplinary international project team, and in an area of unmet need. The opportunity will enable the successful candidate to gain a wide range of advanced expertise and skills including sleep science, cognitive ageing, electrophysiology/EEG, fMRI, behavioural assessment, and advanced computational techniques. While existing experience is advantageous, all training will be provided.