- The ‘glymphatic system’ — the flow of cerebrospinal fluid during sleep to flush out toxins and waste materials from the brain — plays an essential role in keeping the brain healthy.
- A new study, using MRI scans, found that people with cardiovascular risk factors that impaired the function of the glymphatic system had an increased risk of dementia.
- The researchers suggest that improving sleep patterns to enhance glymphatic system function and treating cardiovascular risks could both help reduce dementia risk.
The glymphatic system is a recently discovered waste clearance system, most active during sleep, that removes toxins and waste materials, including those associated with dementia, from the central nervous system.
A new study has found that people with an impaired glymphatic system have a higher risk of developing dementia.
“These findings are largely expected, building on a growing body of research that implicates impaired cerebrospinal fluid (CSF) dynamics, often referred to as the ‘glymphatic system’, in dementia. Animal studies have long shown that disrupted CSF flow hampers the clearance of toxic proteins such as amyloid beta and tau, which are central to Alzheimer’s disease pathology. What makes this study significant is that it provides large-scale, human-based evidence from over 45,000 participants in the UK Biobank, confirming that MRI markers of CSF dysfunction […] are associated with higher dementia risk.”
— Dr Steve Allder, consultant neurologist at Re:Cognition Health, who was not involved in the study.
In their study, researchers used machine-learning algorithms, developed by Yutong Chen, one of the paper’s authors, while a medical student at the University of Cambridge. These algorithms can assess glymphatic functions from multiple MRI (magnetic resonance imaging) scans.
The researchers applied the algorithms to MRI scans from around 45,000 adults. They identified 3 biomarkers, linked to impaired glymphatic function, that predicted dementia risk over the following decade.
The three biomarkers, all of which provide insights into cerebrospinal fluid (CSF) dynamics, were:
- BOLD-CSF coupling — blood oxygen level-dependent cerebrospinal fluid coupling, which tracks the connection between global brain activity and CSF flow.
- DTI-ALPS, a measure of the diffusion of water molecules along the perivascular spaces — passageways along which CSF travels, that surround blood vessels in the brain.
- The size of the choroid plexus — highly folded structures containing many blood vessels, where the CSF is produced.
“This newly published study uses brain imaging to look at different snapshots of the glymphatic system in about 45,000 people from the large UK Biobank. They found three biomarkers related to CSF movement that, in the study population, were predictive of new cases of dementia. These factors were also related to the ways in which heart health issues can contribute to dementia risk.”
— Ozama Ismail, Ph.D., Director of scientific programs at the Alzheimer’s Association, which published the study in its journal
During a median of 5.3 years of follow-up, the researchers recorded 133 cases of incident dementia.
They found that higher DTI-ALPS was associated with a lower dementia risk, whereas lower BOLD-CSF coupling and higher choroid plexus volume were associated with increased dementia risk.
Additionally, they found that several cardiovascular risk factors, such as hypertension, diabetes, smoking and alcohol, all impaired glymphatic function and increased dementia risk.
Allder explained with these findings:
“Cardiovascular diseases such as hypertension, atherosclerosis, and heart failure reduce arterial pulsation and disrupt perivascular flow, as confirmed by this study’s association between higher arterial stiffness and lower DTI-ALPS scores. Diabetes was also identified as a contributor to impaired CSF flow, possibly due to microvascular damage and inflammation.”
Allder told Medical News Today:
“The brain’s waste clearance system, driven by CSF circulation through the perivascular and interstitial spaces, removes metabolic by-products and neurotoxic proteins such as amyloid beta and tau.”
“When this system becomes inefficient, due to reduced CSF flow, vascular stiffness, or choroid plexus dysfunction, waste products accumulate, promoting neuroinflammation, oxidative stress, and neuronal damage. Over time, these processes accelerate cognitive decline and increase dementia risk,” he explained.
This study suggests that improving the flow of CSF may decrease the risk of dementia, so is it possible to enhance brain clearance?
Glymphatic activity is greatly increased during sleep, and suppressed during waking hours. While you are sleeping, the system clears waste products, including potentially neurotoxic products, such as β-amyloid which forms plaques that interfere with nerve transmission in Alzheimer’s disease, from the brain.
“There are emerging strategies to support or improve glymphatic clearance. Good cardiovascular health is key — maintaining optimal blood pressure, managing diabetes and exercising regularly all enhance vascular pulsatility and CSF flow. Quality sleep is also critical, as glymphatic clearance is most active during deep sleep. Avoiding excessive alcohol, staying hydrated and possibly using interventions that improve arterial elasticity (e.g., aerobic fitness, dietary omega-3s) may further help preserve waste clearance efficiency.”
— Steve Allder, MD
So getting a good night’s sleep could be one way to help improve your brain clearance. Experts advise several ways to improve sleep, including exercising daily, maintaining a regular sleep schedule, avoiding large meals, beverages and alcohol near bedtime, and taking time to wind down before bed in the evening.
Allder said that with further validation, the findings could help lead to earlier diagnosis and preventive measures for dementia:
“These findings suggest that MRI-based markers of CSF dynamics — particularly DTI-ALPS, BOLD-CSF coupling, and choroid plexus volume — could become early, noninvasive indicators of dementia risk before cognitive symptoms appear. If validated across diverse populations, these measures could be integrated into routine brain imaging protocols for at-risk individuals, especially those with cardiovascular or metabolic conditions.”
“This would enable earlier identification of people with impaired brain clearance, and open opportunities for preventive interventions targeting vascular health, sleep quality and lifestyle modification. Additionally, these imaging markers could serve as biomarkers in clinical trials, helping to evaluate whether therapies aimed at improving glymphatic flow (such as sleep optimization or vascular therapies) reduce dementia risk or progression,” he told MNT.
“The study adds to our understanding of the complex relationships between vascular changes in the brain, removal of harmful waste, and incident dementia. In this way, it may help us identify future targets for treatment and risk reduction.”
— Ozama Ismail
