A groundbreaking study led by researchers at the University of Cambridge has identified a significant link between impaired cerebrospinal fluid (CSF) movement and an increased risk of dementia. Published today in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association and presented at the World Stroke Congress 2025 in Barcelona, the research utilized data from 40,000 adults in the UK Biobank to establish this connection.
The study focuses on the glymphatic system, a crucial brain function discovered in 2012, which clears toxins and waste from the brain. This system operates by flushing CSF through perivascular spaces, tiny channels around blood vessels, and is thought to protect against dementia by preventing the build-up of toxic substances such as amyloid plaques and tau tangles, characteristic of Alzheimer’s disease.
The Glymphatic System and Dementia
One of the most common forms of dementia, vascular dementia, results from reduced blood flow to the brain, often due to cerebral small vessel disease. This condition not only causes dementia but also exacerbates other forms, as demonstrated by a study of nuns in the US. It found that while only half of those with Alzheimer’s pathology exhibited symptoms, this increased to 90% when cerebral small vessel disease was also present.
Professor Hugh Markus and his team at the University of Cambridge investigated whether cerebral small vessel disease and cardiovascular risk factors damage the glymphatic system, thereby increasing dementia risk. Recent advances in MRI technology, combined with machine learning algorithms developed by Yutong Chen, have made it possible to study glymphatic function in humans on a large scale.
Key Findings and Implications
The research identified three biomarkers linked to impaired glymphatic function: 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. These markers predicted dementia risk over a decade.
“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?” – Yutong Chen, Department of Clinical Neurosciences, University of Cambridge
Further analysis revealed that cardiovascular risk factors impair glymphatic function, increasing dementia risk partly through cerebral small vessel disease. Hui Hong, a radiologist and first author, noted the significance of these findings in understanding Alzheimer’s disease.
Potential Strategies for Risk Reduction
The study suggests several strategies for reducing dementia risk. Improving glymphatic function could be key, with sleep playing a crucial role. Disrupted sleep patterns may impair the system’s ability to clear toxins. Existing medications could potentially be repurposed, or new ones developed, to enhance glymphatic function.
Addressing vascular risk factors, such as high blood pressure, is another approach. The SPRINT MIND trial demonstrated that intensive blood pressure control reduced cognitive decline by 20% compared to standard treatment.
“We already know the importance of cardiovascular risk factors when it comes to dementia, and our findings further emphasize 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.” – Professor Hugh Markus, University of Cambridge
Future Research and Public Health Implications
Professor Bryan Williams, Chief Scientific and Medical Officer at the British Heart Foundation, highlighted the study’s potential to open new research avenues for treating and preventing dementia. He emphasized the importance of managing cardiovascular risk factors to reduce dementia risk.
“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.” – Professor Bryan Williams, British Heart Foundation
The research, funded by the British Heart Foundation and supported by the National Institute for Health and Care Research Cambridge Biomedical Research Centre, underscores the critical role of the glymphatic system in brain health and dementia prevention. As understanding of this system grows, so too does the potential for innovative interventions to mitigate dementia risk.
