Â鶹Éç

The mobility of cerebrospinal fluid (CSF) plays a key role in clearing brain waste products via the glymphatic system, and reduced CSF dynamics have been linked to ageing and neurodegenerative disease. However, no human intervention study has investigated whether CSF-mobility can be modified in ageing, and whether such changes relate to cognitive benefits. Here, this proof-of-concept study will test whether aerobic exercise can modulate cerebrospinal fluid (CSF) mobility in older adults.A sample of healthy older adults will be recruited to a 3-month aerobic exercise intervention or control group (n = 45). 

Using a recently developed 7 Tesla MRI sequence, we will measure CSF-mobility and cognition before and after the intervention. Importantly, we will examine whether exercise-induced changes in CSF mobility relate to cognitive improvements. In a secondary analyses, we will also establish the (currently unknown) test–retest reliability of CSF-mobility in older adults. 

This project will address a critical gap in our mechanistic understanding of how exercise benefits the ageing brain. Success will be defined as a clear answer - positive or null - on whether exercise modulates CSF mobility, alongside demonstration of the feasibility and sensitivity of these measures in an interventional context. Potential obstacles include inter-individual variability and the unknown sensitivity to cognitive and fitness changes. These will be mitigated through reliability testing and complementary physiological measures. 

If successful, this work will lay the groundwork for a fully powered randomised controlled trial with extended follow-up to determine whether targeting CSF-mobility can promote healthy cognitive ageing. Even null results will provide crucial methodological benchmarks for future research using this emerging biomarker, making this a high-risk, high-gain project well suited to the Lundbeck Foundation Experiment grant.