Functional Connectivity Mediates the Impact of Iron Content on Cognition in Women with Suspected Coronary Microvascular Dysfunction

Motivation: Women with ischemia and non-obstructive coronary arteries (INOCA) may experience cognitive decline due to non-heme iron accumulation causing oxidative stress and cell death, but underlying mechanism is still unknown. Goal(s): This study aims to understand how iron affects brain function and cognitive performance in women with suspected INOCA. Approach: By combining high-resolution Quantitative Susceptibility Mapping and resting-state fMRI, the research focused on thalamic iron and its association with brain connectivity and cognitive metrics. Results: Results indicated that thalamic iron impacts cognitive outcomes, particularly executive functions and processing speed, in women with suspected INOCA, with these effects partly mediated by changes in functional connectivity. Impact: This study's insights into iron's cognitive effects may guide early interventions, influence therapeutic strategies for INOCA patients, and prompt further research into the systemic impact of iron on brain connectivity and cognitive health.