Atherosclerosis-often called “hardening of the arteries”-is well known for causing heart attacks and strokes. Emerging evidence now shows that even early!stage arterial thickening can independently drive damage to the brain’s white matter and accelerate declines in memory and thinking skills. While reduced blood flow contributes to this process, the specific blood!borne molecules that carry harmful signals from diseased vessels into the brain remain unknown.
This project will use UK!Biobank’s unrivalled combination of blood biomarkers, imaging and long!term cognitive follow!up to answer one key question: Which circulating molecules link atherosclerosis to later cognitive decline, and can they be used to predict and prevent both heart!artery disease and dementia?
To address this, we will:
1. Profile blood molecules at scale.!Measure hundreds of small!molecule metabolites, thousands of proteins and immune!cell signals in UK!Biobank plasma samples.
2. Connect molecules to scans.!Relate these molecular signatures to artery health (carotid ultrasound, coronary calcium) and to brain MRI measures (white!matter lesions, microstructure, blood flow).
3. Distinguish cause from effect.!Apply genetic and statistical methods to identify molecules that actively drive brain injury rather than simply accompany it.
4. Build an early!warning score.!Integrate key blood markers, imaging features and standard risk factors into a single risk!prediction tool for combined cardiovascular and cognitive outcomes.
By mapping the “metabolite!centred axis” between arteries and brain, we aim to deliver simple blood tests for early detection, highlight new targets for therapies that protect both heart and mind, and enable precision!prevention strategies to reduce the burden of cardiovascular disease and dementia.
