Abstract

The UK Dementia Research Institute (UK DRI) is an initiative funded by the Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. Funding details for UK DRI programmes will be added in 2019. Evidence is building that sleep disturbances in healthy people, repeated over years, might trigger or accelerate pathological processes leading to dementia, e.g. by causing oxidative stress or enhancing amyloid deposition1-5. In healthy middle-aged men, for example, one night of total sleep deprivation produced elevated morning amyloid beta (Ab42) in cerebrospinal fluid (CSF)6. Sleep deprivation over two months of AβPP/PS1 mice caused them to have irreversibly increased amyloid production and more plaques in cortex and hippocampus and elevated neuronal mitochondrial damage and apoptosis6. Sleep restriction (6 hrs/day for 6 weeks) of 3xTg mice elevated amyloid and pTau in neocortex7; milder sleep restriction of the same strain (4 hours per day for 8 weeks) increased the amount of insoluble tau, and decreased the level of synaptic markers (PSD95)8. Once amyloid pathology has formed in the NREMgenerating areas of the prefrontal cortex, the area of cortex that is responsible for generating delta waves, this could further disrupt NREM sleep, leading to a vicious cycle of sleep disruption and more amyloid deposition9.