Alzheimer’s Disease is the most common form of dementia. In the UK dementia and Alzheimer disease were the leading cause of death in England and Wales (ONS figures, 2018). Global costs exceed $1 trillion, a figure that can only increase as people live longer.
There is a strong correlation between age and onset of the disease, although there are some rare variants that can strike younger people. Currently there are more than 20 million people suffering from Alzheimer’s -a number that is expected to double by 2040- as the global population ages.
As well as memory loss, other symptoms include difficulty sleeping, agitation, psychosis, mood swings and sometimes aggressive behaviour. Caring for sufferers is a huge burden for both individuals and society.
The disease pathophysiology is characterised by protein deposits of amyloid (plaques) and Tau (tangles). These have been the targets of much of the clinical research so far undertaken. Our approach is to target not only the most distressing symptoms of the disease, but to explore what may be the underlying cause. By increasing and improving the quality of non-REM sleep, we expect not only to alleviate symptoms, but also to enhance the ability of the brain to “clean” itself and to remove unwanted waste materials.
See this video of what happens when we sleep.
Slow-wave or non-REM sleep is a deep sleep considered to be important for processes such as memory consolidation and growth hormone secretion. Recent advances in sleep imaging have also demonstrated it to be the key sleep phase for pulsatile cerebrospinal fluid driven clearance from the brain.
The glymphatic system is a clearance system that eliminates waste soluble proteins and metabolites from the central nervous system. The science behind the discovery and imaging of the glymphatic system is new. The impact of aging on this process and its relationship to deep sleep are also recent discoveries.
An excellent introduction to the glymphatic system is to be found here. Further discussion is presented here. Sleep disruption and CNS build up of unwanted proteins and metabolites are features of several neurological disorders, most notably Alzheimer’s Disease. The hypothesis that significant enhancement of slow-wave sleep would promote waste clearance and ameliorate disease has yet to be clinically tested.
- Obstructive sleep apnea treatment, slow wave activity, and amyloid-β (2019, Holtzmann et al)
- Glymphatic failure as a final common pathway to dementia (2020, Nedergaard et al)
- Sleep symptoms in syndromes of frontotemporal dementia and Alzheimer’s disease: A proof-of-principle behavioural study (2019, Dijk et al)
- Sleep, Cognitive impairment, and Alzheimer’s disease: A Systematic Review and Meta-Analysis (2017, Bubu et al)
- Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation (2016, Nedergaard et al)
- Increased glymphatic influx is correlated with high EEG delta power and low heart rate in mice under anesthesia (2019, Hablitz et al)
- Effect of 1 Night of Total Sleep Deprivation on Cerebrospinal Fluid β-Amyloid 42 in Healthy Middle-Aged Men: A Randomized Clinical Trial (2014, Ooms et al)
- Aberrant waste disposal in neurodegeneration: why improved sleep could be the solution (2021, Wafford)