Research

Can you sleep your way to a healthier brain?

Poor sleep and dementia are common bedfellows. People with dementia often experience disrupted sleep, which can affect their and their carers' quality of life. In recent years, it has also been suggested that people with regular sleeping problems are at a greater risk of developing dementia. The nature of these studies makes it difficult to know what comes first - does poor sleep contribute to the development of dementia, or is it an early indication that disease is developing in the brain?

The UK Dementia Research Institute (UK DRI) has been established with funding from the Medical Research Council, Alzheimer's Society and Alzheimer's Research UK to get to grips with the fundamental causes of dementia, and sleep is one of the topics under investigation.

Fresh perspectives

Professors Bill Wisden and Nick Franks have been studying the science of sleep at Imperial College London for almost a decade. Now for the first time, within the UK DRI, they're turning their attention to dementia.

'We're definitely bringing a left-field approach; most of us at the UK DRI Imperial centre don't have a background in dementia. The institute provides the right framework for unique collaboration, allowing us to learn from dementia experts while we bring new perspectives and techniques to the table,' explains Professor Wisden.

Their research into the role of sleep in dementia is only just beginning, but being part of the UK DRI is already changing their thinking about the brain. Professor Wisden says it's important to understand dementia in terms of how different parts of the brain work together.

'Even though I'm a professional neuroscientist, I've never had to think so deeply before about the brain as an organ,' he says. 'It's packed full of blood vessels and multiple cell types all working together. Dementia needs to be thought of as a problem of organ physiology, not just a problem of proteins and molecules.'

Why do we sleep?

We all know the effects of a bad night's sleep. Along with physical tiredness, you feel groggy and can experience changes in mood, memory and how quickly you're able to think. You can usually catch up on sleep the next night, but research in mice suggests long-term sleep deprivation can cause lasting damage to the brain that isn't recovered.

Sleep is clearly a vital behaviour but, despite decades of research, scientists still can't agree its purpose. Some argue that it is necessary to reset connections between brain cells and suggest that while we sleep we process information from the previous day, allowing us to form new memories.

Another theory states that sleep exists to repair damage in the body and brain that has accumulated while awake.

This last theory is gaining more traction following a discovery in 2013 that the brain flushes out waste toxins during sleep.

'Our brains don't have the same lymphatic draining system as other organs of the body,' says Professor Wisden. 'Toxins and waste are cleared out along the outside of walls of blood vessels, in the space made between the vessels themselves and other types of cell, called glial cells. There is evidence to suggest this clearing process happens more when we are sleeping.'

Clearing out faulty proteins

Many forms of dementia including Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies, involve the accumulation of faulty proteins in or around brain cells. If sleep is essential for clearing our damaged proteins from the brain, then it makes sense that long-term sleep disruption could increase or worsen the conditions that cause dementia.

Professor Wisden and Professor Franks want to confirm that the brain's waste disposal system is indeed more active during sleep and then find a clear mechanism for how this process works. 'Once we know the mechanism, we can start thinking about how to enhance protein clearance as a potential way to treat neurodegenerative diseases,' says Professor Wisden.

The researchers will use cutting edge microscopy techniques to follow the movement of proteins in the brains of live, behaving mice. They'll track how quickly proteins move into the blood vessels when mice are asleep and awake, and also after periods of disrupted sleep.

'It's actually really easy to stop a mouse from sleeping. You just keep presenting it with novel objects and the mouse is so interested in exploring them that it doesn't go to sleep.'

Enhancing waste disposal

Professors Wisden and Franks have discovered a type of brain cell that is more active when the mice go to sleep, but that doesn't seem to play a role in controlling the sleep-wake cycle. They are going to artificially activate these cells and see what they do, hoping to reveal a critical role in the waste disposal process.

'The ultimate goal of our research might be treatments that can mimic sleep processes in the brain,' says Professor Wisden.

They will also be working with Dr Nir Grossman, an engineer by background who has recently joined the UK DRI at Imperial College London as a UK DRI Fellow. Dr Grossman has developed a new technique to induce brain waves in small areas of the brain by passing electrical currents through the scalp.

Working together, the team will generate the brain waves of sleep (called delta waves) in awake mice to see if they can artificially stimulate the brain's waste disposal system. As the technique is non-invasive, it has the potential to be used in people if their results show promise.

Professor Wisden acknowledges that sleep will not be the whole story when it comes to dementia. After all, people who get a full night's sleep can still go on to develop the condition.

The UK DRI at Imperial College London is looking broadly at the environmental factors that might influence the development of dementia.

In the long term, the team hope that by understanding how factors such as sleep play a role in the disease process, they can develop ways to remove their effects and ultimately delay or prevent the onset of dementia.