A groundbreaking study led by researchers at the University of Cambridge has revealed a significant link between impaired movement of cerebrospinal fluid (CSF) and the risk of developing dementia later in life. Published today in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, the findings are also being presented at the World Stroke Congress 2025 in Barcelona. This extensive research involved 40,000 adults from the UK Biobank, offering new insights into the brain’s waste clearance system and its role in dementia.
The study highlights the importance of the glymphatic system, a network responsible for flushing CSF through the brain to remove toxins and waste. Discovered in 2012, this system functions by channeling CSF along perivascular spaces, effectively cleaning the brain. Disruption of this system has now been linked to common forms of dementia, including Alzheimer’s disease, which is characterized by the accumulation of amyloid plaques and tau tangles in brain tissue.
The Glymphatic System and Dementia
One of the most prevalent forms of dementia is vascular dementia, often caused by reduced blood flow to the brain due to cerebral small vessel disease. This condition not only contributes to vascular dementia but also exacerbates other types of dementia. For instance, a study involving nuns in the US showed that while only half of those with Alzheimer’s pathology exhibited dementia symptoms, this number rose to nine in ten when cerebral small vessel disease was also present.
Professor Hugh Markus and his team at the University of Cambridge sought to determine whether cerebral small vessel disease and other cardiovascular risk factors could damage the glymphatic system, thereby increasing dementia risk. Until recently, studying the glymphatic function was limited to mice, but advancements in MRI technology have allowed researchers to assess it indirectly in humans.
Innovative Research Methods
Yutong Chen, a former medical student at Cambridge, developed machine learning algorithms to analyze glymphatic functions from MRI scans on a large scale. Applying these algorithms to MRI scans from 40,000 UK Biobank participants, the team identified three biomarkers associated with impaired glymphatic function. These included DTI-ALPS, a measure of water molecule diffusion along perivascular spaces, the size of the choroid plexus where CSF is produced, and the flow velocity of CSF into the brain.
Yutong Chen stated, “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 us to ask: how can we improve this?”
Cardiovascular Risk Factors and Glymphatic Function
The study further revealed that several cardiovascular risk factors, such as high blood pressure, impaired glymphatic function, and increased dementia risk. This impairment was partly due to cerebral small vessel disease, as visible in MRI scans. First author Hui Hong, now a radiologist at the Second Affiliated Hospital of Zhejiang University in China, emphasized the significance of these findings.
“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,” Hong explained.
Potential Strategies for Risk Reduction
The research suggests several potential strategies for reducing dementia risk. One approach is to improve glymphatic function, possibly through better sleep patterns, as sleep is crucial for this system. Existing medications might be repurposed, or new ones developed, to enhance glymphatic function. Additionally, addressing vascular risk factors such as high blood pressure could be beneficial.
The SPRINT MIND trial supports this approach, demonstrating that intensive blood pressure control led to a 20% reduction in cognitive decline or dementia compared to standard treatment. Professor Markus emphasized the importance of managing cardiovascular risk factors, noting that at least a quarter of all dementia risk is accounted for by common factors like blood pressure and smoking.
Professor Bryan Williams, Chief Scientific and Medical Officer at the British Heart Foundation, remarked, “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.”
Implications for Future Research
This research opens new avenues for understanding and potentially preventing dementia. By improving our knowledge of the glymphatic system, scientists can explore innovative treatments and preventive measures. The study underscores the critical role of managing cardiovascular health in reducing dementia risk.
Funded by the British Heart Foundation, with additional support from the National Institute for Health and Care Research Cambridge Biomedical Research Centre, this study marks a significant step forward in dementia research. As scientists continue to unravel the complexities of the brain’s waste clearance system, the potential for groundbreaking advancements in dementia prevention and treatment grows ever closer.
