Why sleeping well can help keep dementia at bay

WHEN I was at medical school, we were taught about the lymphatic system — a series of channels within the body that drain fluid from the tissues back into the circulation. Roughly three litres of fluid pass through this system each day, helping to remove waste substances and toxins.

At the time, we were told that the one organ that did not have a lymphatic system was the brain.

But, in the past few years — and it is remarkable that it is so recent — it’s been discovered that in fact there is a network of tiny channels in the brain, that have been termed the glymphatic system.

These act like a waste disposal chute for the brain, and there is clear evidence that one of the substances cleared by this network is the protein beta-amyloid.

A build-up of this compound is one of the characteristics of Alzheimer’s disease. The protein forms plaques that cause signalling problems between nerve cells in the brain, triggering inflammation.

But what has this to do with sleep? Well, evidence from sleeping or anaesthetised mice shows that the channels of the glymphatic system expand during sleep, and the flow of fluid through this network increases.

In humans, levels of betaamyloid in the cerebrospinal fluid found in the brain and spinal cord, where the fluid inside the glymphatic vessels ends up, are highest in the morning, suggesting a similar flushing-out.

In fact, a recent study in humans has shown that after even a single night of sleep deprivation, levels of beta-amyloid in certain parts of the brain, including the hippocampus (which is involved in both short and long-term memory, and which is often damaged in Alzheimer’s) go up.

So sleep deprivation could well carry an increased risk for Alzheimer’s disease.

Deep sleep, in particular, seems to be important for the brain’s housekeeping work.

In deep sleep, the glymphatic channels open up by up to 60 per cent, thereby allowing the carriage of potentially toxic substances such as beta-amyloid away from the brain.

This may go some way to explain why sleep apnoea not only appears to cause significant deterioration in various aspects of cognition, such as attention, reasoning and problem-solving, but may also have a direct role in the development of dementia.

In the elderly, a build-up of betaamyloid has been associated with sleep apnoea, and treating sleep apnoea in those with Alzheimer’s seems to improve cognition.

If you consider that in sleep apnoea, sleep is disrupted, sometimes hundreds of times per night, it is easy to understand why this might impair the functioning of the glymphatic system, why betaamyloid levels in the brain might go up, and why this might predispose to Alzheimer’s.

The reality of this association between poor sleep and Alzheimer’s is yet to be fully unravelled. In fact, there is an alternative explanation: many degenerative disorders of the brain result in subtle changes years or even decades before symptoms become more obvious.

It may be that in Alzheimer’s, early changes to the biochemical pathways in the brain years before memory deteriorates result in worsening sleep. In other words, it may be that the poor sleep is not the cause of Alzheimer’s but the result of the very early stages of the disease.

Indeed, this may be a possible explanation for why many older hypnotic drugs that used to be the mainstay for insomnia — particularly benzodiazepines — have been found to increase the risk of subsequent dementia. Given how common both Alzheimer’s disease and sleep apnoea are, and increasingly so, some researchers have proposed that sleep apnoea is a major modifiable risk factor for Alzheimer’s. If sleep apnoea is identified and treated at an early stage, could this be a preventative treatment for Alzheimer’s?