Brain fluid circulation can predict dementia long before memory problems arise

A major international study has uncovered a new biological clue that could help predict dementia long before memory problems arise. Researchers from the University of Cambridge and Zhejiang University found that the way cerebrospinal fluid—known as CSF—moves through the brain may reveal who’s at risk years in advance.

Using MRI scans from more than 45,000 adults in the UK Biobank, the team discovered that changes in how this clear brain fluid circulates were powerful indicators of future dementia. In fact, some of these fluid flow markers were even more predictive than traditional heart and blood vessel risk factors.

The findings, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, shed new light on how the brain’s “cleaning system” connects with cardiovascular health—and how that link could explain the gradual buildup of harmful waste in aging brains.

CSF isn’t just a cushion for the brain—it plays a vital housekeeping role. Constantly circulating through narrow channels and spaces surrounding blood vessels, this fluid helps remove metabolic waste and maintain stable pressure inside the skull.

In healthy brains, this circulation supports a process called the glymphatic system, discovered only in 2012. Acting like a washing network, it flushes toxins through microscopic perivascular spaces and out of the brain. When this system falters, proteins such as amyloid-beta and tau—the culprits behind Alzheimer’s disease—can start to pile up.

Dr. Hui Hong, who led the study as part of her work at Cambridge and now at Zhejiang University, explained that earlier animal studies hinted at a connection between heart health and brain fluid movement, but evidence in humans was lacking. “We wanted to know whether the same relationship existed in people—and whether we could detect early dysfunction before dementia takes hold,” Hong said.

The research team, working with Professor Hugh S. Markus from Cambridge’s Department of Clinical Neurosciences, wanted to see if cardiovascular conditions like high blood pressure and diabetes could interfere with CSF flow and increase dementia risk.

They developed four MRI-based measurements to capture different aspects of CSF movement:

After excluding people with prior neurological conditions, the researchers tracked who later developed dementia. The results were striking.

Three of the four MRI indicators strongly predicted future dementia. People with slower microscopic water movement (low DTI-ALPS), weaker coordination between blood and CSF flow (low BOLD-CSF coupling), or larger choroid plexus volumes were far more likely to develop cognitive decline years later.

These fluid-flow disruptions remained significant even after accounting for age, education, and brain size. “This suggests that CSF dysfunction may be one of the earliest measurable signs of dementia,” said Professor Markus.

One of the most revealing markers, the DTI-ALPS score, pointed to slower movement of water molecules along the brain’s tiny blood vessels—a sign that waste clearance was becoming inefficient. Meanwhile, an enlarged choroid plexus might signal inflammation or overproduction of CSF, further stressing the system.

The study also examined how cardiovascular risk factors affect CSF circulation. High blood pressure, diabetes, and the presence of white matter hyperintensities—bright spots on MRI scans that indicate small vessel disease—were all tied to slower or less organized CSF flow.

Advanced statistical analyses showed that two MRI markers, DTI-ALPS and CP volume, partially explained how heart disease leads to dementia. In essence, vascular issues seemed to interfere with the brain’s ability to drain waste, acting as a biological bridge between cardiovascular decline and cognitive loss.

Professor Markus noted that this finding strengthens the argument for preventive care. “At least a quarter of dementia risk can be traced to common factors like high blood pressure and smoking,” he said. “If these also impair CSF flow, then managing them may help keep the brain’s cleaning system running efficiently.”

A key advance in this research came from a machine learning algorithm developed by Yutong Chen at Cambridge. It allowed scientists to process massive MRI datasets quickly and consistently—something that would have been nearly impossible by hand.

“Automated MRI analysis means we can measure subtle fluid-flow changes across tens of thousands of people,” Chen said. “That’s crucial for spotting early problems while the brain is still healthy.”

This large-scale capability opens the door to future population screenings. Doctors might one day use CSF-based MRI markers to flag early warning signs, much like cholesterol tests identify cardiovascular risk.

The study’s findings also offer new ways to think about dementia prevention. The glymphatic system is most active during deep sleep, when brain cells shrink slightly to allow CSF to flow more freely. Poor sleep habits, therefore, may reduce the brain’s ability to clear harmful proteins.

Lifestyle and vascular health also play major roles. Intensive blood pressure control, for instance, has already been shown to lower cognitive decline risk by as much as 20%. That insight could inspire new strategies that combine cardiovascular management with interventions to improve CSF circulation.

Though this research doesn’t yet prove cause and effect, it highlights a powerful biological link between heart and brain health. The team hopes that further studies will confirm whether improving CSF movement can actually prevent or delay dementia.

Professor Markus said future work might test whether treatments aimed at improving blood vessel function or sleep quality could help restore CSF flow. “If we can find ways to boost the brain’s own cleaning system, we might be able to slow or even stop the progression of dementia,” he said.

Dr. Bryan Williams, Chief Scientific and Medical Officer at the British Heart Foundation, which helped fund the research, added that the study “offers a fascinating glimpse into how silent problems in the brain’s waste removal system may quietly increase dementia risk.”

These findings could help doctors identify at-risk individuals long before symptoms appear, offering a critical window for prevention.

MRI-based markers of CSF flow could serve as new early-detection tools, guiding interventions that focus on cardiovascular health, better sleep, and perhaps new drugs that enhance the brain’s waste-clearing ability.

By understanding how heart and brain systems interact, scientists are moving closer to predicting—and one day preventing—the world’s most common neurodegenerative disorder.

Research findings are available online in the journal Alzheimer's & Dementia.

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