The glymphatic system clears protein waste products from our brain when we sleep, but impaired or insufficient sleep can lead to waste products accumulating in the brain, increasing the risk of developing dementia.
A good night’s sleep definitely improves our mood the next day.
Sleep is the foundation for good physical and mental health. Less than a decade ago, Danish and other researchers discovered that one reason sleep provides benefits is a special system in the brain that removes waste products while we sleep. However, impaired or insufficient sleep enables these waste products to accumulate in the brain instead.
This mechanism Is called the glymphatic system and is now associated with the risk of developing dementia. The glymphatic system works poorly if sleep is impaired and these dementia-associated waste products in the brain are not cleared at night but accumulate instead. This leads to poor long-term outcomes.
An article on the association between sleep, the glymphatic system and dementia was recently published in Science.
“The article consolidates the consensus in this field that the glymphatic system plays an important role in the onset of dementia. So much evidence now indicates that various factors can adversely affect the glymphatic system and result in cognitive impairment, so the association is clear,” explains Maiken Nedergaard, Professor, Center for Translational Neuromedicine, University of Copenhagen.
Science commissioned Maiken Nedergaard to write a review article on the current knowledge in this field.
The brain’s fluid transport system clears waste products between brain cells
The glymphatic system clears protein waste products from the brain when we sleep.
Many waste products from various biological processes accumulate in the brain during the day, and these must be removed to reduce the burden on the brain.
The glymphatic system is highly organized for transporting and clearing cerebrospinal fluid through the glymphatic pathway. This uses perivascular spaces – open fluid-filled tunnels on the outside of the arteries – that flush the waste products away from between the brain cells.
The glymphatic system also involves the water channel protein aquaporin, which is present throughout the brain but was nevertheless first discovered in the early 21st century.
Maiken Nedergaard helped to pioneer research into this relatively recent discovery of the glymphatic system.
Sleep clears waste products from the brain
The glymphatic system works optimally and almost exclusively while we sleep.
Various factors can therefore influence both sleep and the brain’s ability to remove the harmful waste: age, sleep quality, substance abuse, depression, cardiovascular disease, inactivity, sleep apnoea, obesity and disruption of the circadian rhythm.
If too many negative factors are present, waste is not removed from the brain at night and can accumulate over time.
“Almost all diseases reduce the quality of sleep, and an interesting perspective is that almost all neurodegenerative disorders such as dementia and Alzheimer’s start with patients having difficulty sleeping. Sleep problems occur even before memory loss begins,” explains Maiken Nedergaard.
People with Alzheimer’s have impaired sleep
Maiken Nedergaard explains that the first symptom many patients with Alzheimer’s have is difficulty sleeping.
Many people who end up in nursing homes do so because their sleep patterns are so misaligned with their circadian rhythm that their families have difficulty in taking care of them.
They may take long naps during the day and stay awake most of the night.
“Sixty-five percent of the people with Alzheimer’s are placed in institutions because they are awake at night and their families cannot take care of them. This shows a clear link between sleep and dementia, and suggest that the the glymphatic system plays an important role,” says Maiken Nedergaard.
Clearing waste products that can cause Alzheimer’s and Parkinson’s
Maiken Nedergaard’s review article links the development of Alzheimer’s and Parkinson’s with the effects of glymphatic dysfunction.
Amyloid-beta and phosphorylated tau proteins accumulate in the brain of people with Alzheimer’s, and people with Parkinson’s accumulate alpha-synuclein.
When the glymphatic system does not clear these protein waste products from the brain and they are allowed to accumulate, the brain can develop these neurodegenerative disorders.
“The glymphatic system plays a role in several diseases in which the person has diminished cerebrospinal fluid flow. Age is associated with a significant decrease in sleep quality and decreased glymphatic flow. This reduced flow prevents the extracellular protein waste from being removed from the brain, where it accumulates, leading to local inflammation, loss of neurons and ultimately dementia,” explains Maiken Nedergaard.
A pathway for early diagnosis of dementia?
According to Maiken Nedergaard, the research can be used to develop methods for diagnosing dementia at a very early stage.
Other clinical studies have shown that dementia is often diagnosed today because of memory loss, and then it is already too late to do anything about it.
However, a magnetic resonance imaging scan of the brain showing impaired function of the glymphatic system may indicate that the brain is not clearing the waste products that could lead to dementia in a few years.
“Scanning enables us to determine whether new treatments can improve the glymphatic system and thus reduce the risk of developing dementia, so we will not have to wait for 10 or 20 years to see whether these people develop dementia or not,” says Maiken Nedergaard.
Drugs might alter fluid flow in the brain
Maiken Nedergaard elaborates that the emerging new knowledge also indicates that drugs might help the glymphatic system.
Such a boost could counteract many neurodegenerative disorders and could also optimize the glymphatic system to reduce the need for sleep.
Maiken Nedergaard says that examining whether some existing drugs improve the glymphatic system or definitely reduce fluid flow in the brain is already relevant.
“This is exactly what the United States armed forces are investigating. Improving sleep for a few hours so that the glymphatic system can clear waste products from the brain will not only enable us to manage with less sleep but also make sleep more effective in keeping the brain healthy and well,” concludes Maiken Nedergaard.
