Yalda Amirmoezzi, Vanessa Cropley, Andrew Zalesky, Ye Ella Tian
Cardiovascular risk (CVR) factors exert effects that extend beyond the vascular system, influencing brain structure, neural function, and cognitive performance. The mechanisms by which CVR factors exert these effects remain unclear. Here, we specifically investigate the impact of CVR factors on brain aging, testing whether quantitative measures of the heart and major arteries mediate the CVR-brain-age relationship. Using longitudinal UK Biobank data, we infer individual brain age estimates based on neuroimaging-derived measures and apply pathway analysis to quantify whether cardiovascular imaging phenotypes mediate the impact of eight established CVR factors on brain aging. Our findings reveal that structural characteristics of the aorta and carotid arteries, specifically the ascending and descending aortic areas and carotid thickness, mediate the effects of the Framingham risk score, a cumulative measure of CVR factors, on the rate of brain aging and cognitive decline. When examining individual CVR factors separately, elevated total cholesterol level was found to accelerate brain aging by affecting the aorta and carotid structures. Our findings highlight the cardiovascular characteristics, particularly vascular structure, as a potential target for early intervention to prevent or delay brain aging and cognitive decline.