Abstract
Mental and nervous system disorders often co-occur with cardiovascular diseases in aging populations, yet the biological relationships underlying these associations remain incompletely understood. Using heart and brain imaging data from 33,573 UK Biobank (UKB) participants, we developed a brain age prediction model to estimate the brain age gap (BAG), an imaging-based marker of brain aging. We then examined BAG as a mediator between 82 cardiac imaging-derived phenotypes (IDPs) and 11 disorders. Sixty-one cardiac IDPs, particularly those related to the atria and left ventricle, were significantly associated with BAG, with several also related to mental and nervous system disorders. Mediation analyses revealed that BAG significantly mediated 18 associations between heart and substance abuse, mood, and neurotic disorders. Furthermore, we observed a total of 49 significant associations, where lifestyle factors, including smoking and physical activity, were related to heart-brain aging-disorder relationships. These findings highlight brain aging as a potential pathway linking cardiovascular health to diverse brain disorders in aging populations.