Summary: Researchers have discovered that problems with the brain’s waste-clearing system—the glymphatic system—may significantly raise the risk of developing dementia. In one of the largest studies to date, MRI data from 40,000 adults revealed that impaired cerebrospinal fluid (CSF) flow predicts dementia risk years before symptoms appear.
The findings show that cardiovascular issues like high blood pressure can damage this system, worsening toxin buildup in the brain. Improving sleep quality and managing blood pressure could help keep this system functioning and lower dementia risk.
Key Facts:
- Waste Clearance Link: Impaired glymphatic system function predicted dementia risk in 40,000 adults.
- Cardiovascular Impact: High blood pressure and other vascular risk factors disrupted brain waste flow.
- Preventive Potential: Good sleep and blood pressure control may protect glymphatic function and reduce dementia risk.
Source: University of Cambridge
Problems with the brain’s waste clearance system could underlie many cases of dementia and help explain why poor sleep patterns and cardiovascular risk factors such as high blood pressure increase the risk of dementia.
A study led by researchers at the University of Cambridge found that impaired movement of cerebrospinal fluid (CSF) – the clear liquid that cushions and cleans the brain – predicted risk of dementia later in life among 40,000 adults recruited to the UK Biobank.
Their findings are published today in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
In the healthy brain, the so-called glymphatic system serves to clear out toxins and waste materials, keeping the brain healthy. Only discovered as recently as 2012, this system functions by flushing CSF through the brain along tiny channels around blood vessels known as perivascular spaces. It collects waste then drains out of the brain, helping keep it clean and healthy.
The glymphatic system is thought to be important in protecting against many of the common forms of dementia, which are often characterised by the build-up of toxic substances in the brain – for example, Alzheimer’s disease sees amyloid ‘plaques’ and tau ‘tangles accumulate in brain tissue.
One of the most common forms of dementia is vascular dementia, caused by reduced blood flow to the brain. The most common cause of this type of dementia is cerebral small vessel disease, which affects the small blood vessels in the brain.
But the impact of cerebral small vessel disease is even greater because it also interacts with other dementias making them worse; for example, a study of nuns in the US found that among those nuns whose brains showed signs of Alzheimer’s disease post mortem, only around a half exhibited symptoms of dementia – but this increased to around nine in 10 if they also had cerebral small vessel disease.
Professor Hugh Markus and colleagues at the University of Cambridge wanted to see whether cerebral small vessel disease and other cardiovascular risk factors damage the glymphatic system – and whether this in turn increases the risk of dementia.
Until recently, it has only been possible to study glymphatic function in mice, but recent advances in MRI scanning have made it possible to study it indirectly in humans. Even so, it was only possible to do this practically in relatively small numbers, but Yutong Chen, while a medical student at the University of Cambridge, developed machine learning algorithms capable of assessing glymphatic functions from MRI scans at scale.
The team applied the algorithm to MRI scans taken from around 40,000 adults in UK Biobank. They found three biomarkers – biological signatures – associated with impaired glymphatic function assessed at baseline, predicted the risk of dementia occurring over the subsequent decade.
One of these was DTI-ALPS, a measure of the diffusion of water molecules along the perivascular spaces. Another was the size of the choroid plexus, where the CSF is produced. The third measure reflected the flow velocity of CSF into the brain.
Yutong Chen, from the Department of Clinical Neurosciences at Cambridge, said: “Although we have to be cautious about indirect markers, our work provides good evidence in a very large cohort that disruption of the glymphatic system plays a role in dementia. This is exciting because it allows to ask: how can we improve this?”
Further analysis showed that several cardiovascular risk factors impaired glymphatic function – and hence increased dementia risk, and that this was partly via causing cerebral small vessel disease, which is visible in the MRI scans.
First author Hui Hong, now a radiologist at the Second Affiliated Hospital of Zhejiang University, Hangzhou, China, said: “We already have evidence that small vessel disease in the brain accelerates diseases like Alzheimer’s, and now we have a likely explanation why. Disruption to the glymphatic system is likely to impair our ability to clear the brain of the amyloid and tau that causes Alzheimer’s disease.”
The research suggests possible approaches for reducing dementia risk. One is to look at strategies for improving glymphatic function. Sleep plays an important role in glymphatic function, and so disrupted sleep patterns are likely to impair its ability to clear toxins. Alternatively, there may be existing medicines that could be repurposed, or new ones that could be developed, to improve glymphatic function.
Another possible approach is to treat vascular risk factors such as high blood pressure. This is supported by recent studies: the SPRINT MIND trial, for example, showed that intensive blood pressure control (maintaining a systolic blood pressure of less than 120 mm Hg) led to a 20% reduction in cognitive decline or dementia compared to participants in the standard treatment group.
Professor Markus, who leads the Stroke Research Group at the University of Cambridge and is a Fellow of Clare Hall, Cambridge, said: “We already know the importance of cardiovascular risk factors when it comes to dementia, and our findings further emphasise this link.
“At least a quarter of all dementia risk is accounted for by common risk factors like blood pressure and smoking. If these impair glymphatic function, then we can intervene. Treating high blood pressure or encouraging people to stop smoking would be an achievable way to helping the glymphatic system work better.”
Professor Bryan Williams, Chief Scientific and Medical Officer at the British Heart Foundation, said: “This study offers us a fascinating glimpse into how problems with the brain’s waste clearance system could be quietly increasing the chances of developing dementia later in life.
“By improving our understanding of the glymphatic system, this study opens exciting new avenues for research to treat and prevent dementia. It also emphasises the importance of managing known cardiovascular risk factors, such as high blood pressure, for reducing dementia risk.”
Funding: The research was funded by the British Heart Foundation, with additional support from the National Institute for Health and Care Research Cambridge Biomedical Research Centre.
Key Questions Answered:
A: The glymphatic system is the brain’s cleaning network that flushes out toxins and waste through cerebrospinal fluid (CSF). Disruption of this system can lead to toxin buildup, potentially contributing to dementia.
A: High blood pressure and small vessel disease impair glymphatic flow, reducing the brain’s ability to remove waste such as amyloid and tau proteins associated with Alzheimer’s disease.
A: Yes. The study suggests that deep, regular sleep and treating vascular risk factors may enhance waste clearance in the brain, offering practical ways to protect against cognitive decline.
About this dementia and neurology research news
Author: Craig Brierley
Source: University of Cambridge
Contact: Craig Brierley – University of Cambridge
Image: The image is credited to Neuroscience News
Original Research: Open access.
“MRI markers of cerebrospinal fluid dynamics predict dementia and mediate the impact of cardiovascular risk” by Hugh Markus et al. Alzheimer’s & Dementia
Abstract
MRI markers of cerebrospinal fluid dynamics predict dementia and mediate the impact of cardiovascular risk
INTRODUCTION
Impaired cerebrospinal fluid (CSF) dynamics may contribute to dementia, but human evidence is limited. We examined associations between magnetic resonance imaging–based proxies of CSF dynamics and incident dementia, and whether CSF dysfunction mediates links between cardiovascular risk and dementia.
METHODS
Using the UK Biobank, we measured CSF dynamics: perivascular space (PVS) volume, diffusion tensor image analysis along the PVS (DTI-ALPS), blood oxygen level–dependent CSF (BOLD-CSF) coupling, and choroid plexus (CP) volume. We assessed cardiovascular risk factors and their associations with CSF dynamics and dementia based on general practitioner, mortality, and hospital records. Mediation analysis evaluated CSF dysfunction in cardiovascular risk–dementia relationships.
RESULTS
Lower DTI-ALPS, lower BOLD-CSF coupling, and higher CP volume predicted dementia, but PVS volume did not. DTI-ALPS and CP volume mediated the effect of white matter hyperintensities and diabetes duration on dementia.
DISCUSSION
Impaired CSF dynamics may lead to dementia and partially mediate cardiovascular risk–dementia associations.
