Clogged Glymphatic System Linked to Dementia Risk

The brain’s built-in clearance system, called the glymphatic system, removes toxins from the brain through the flow of cerebrospinal fluid (CSF) via minuscule channels that trace blood vessels. Scientists have suspected that the glymphatic system may play a role in processes such as sleep and recovery from traumatic brain injury.

Now, researchers led by Hugh Markus, a neurologist at the University of Cambridge, used data from the massive UK Biobank resource and found a link between reduced glymphatic function and increased risk of dementia. Their findings, published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, highlight why impaired cardiovascular function—which is closely tied with the glymphatic system—and poor sleep associate with dementia risk.¹

The Challenge of Studying the Brain’s Waste System

Researchers have suspected that reduced glymphatic flow—and consequently, reduced waste clearance—plays a role in the development of dementias like Alzheimer’s disease, wherein toxic protein plaques accumulate in the brain.² But much of the research to support this theory came from animal models, where scientists could invasively analyze CSF movement.

However, with advances in imaging technology, researchers proposed that data mined from magnetic resonance imaging (MRI) scans of the brain could indicate glymphatic function. Previous studies have examined some of these data, but only in small samples.³

Markus and his team examined MRI data from the longitudinal UK Biobank cohort, using a sample size of tens of thousands of scans. Machine learning algorithms pioneered by study co-author Yutong Chen, who worked on the project during his medical degree, were key to unlocking this data resource.

Identifying Glymphatic Biomarkers

The team found that three biomarkers linked to impairments in glymphatic function predicted dementia onset in the following ten years. These were CSF velocity as it flowed into the brain, the volume of the choroid plexus (a blood vessel network that produces CSF), and a measure of water diffusion along the brain’s perivascular spaces.

The team expressed guarded optimism about their findings. “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?” said Chen in a press release.

The glymphatic system is closely tied to the brain’s vascular system. Damage to small blood vessels and dysfunction in blood flow in the brain exacerbates dementia symptoms. According to the team, their results suggest glymphatic disruption mediates this effect.

Further, they suggested that treatments to improve the function of the glymphatic system or vascular risk factors like high blood pressure, which can damage blood vessels, could produce long-term reductions in dementia risk.

“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,” Markus said in the press release.