Atrial Fibrillation, Brain Structure and Cognitive Function: A Mediation Analysis

Abstract

Background and Objectives: Atrial fibrillation (AF) is associated with an increased risk of cerebrovascular disease and cognitive impairment. However, evidence on the mediating role of brain structural changes in this association remains limited, especially in Asian populations. This study investigated the associations among AF, magnetic resonance imaging (MRI)-measured brain structures, and cognitive function, and evaluated the mediation effect of brain structural changes in the AF-cognition link. Methods: Two thousand, six hundred sixty-two participants from the KoGES-CAVAS-C cohort were analyzed, who without a history of stroke or missing data. AF was identified with electrocardiograms and confirmed by cardiologists. Cognitive function was assessed using the Seoul Neuropsychological Screening Battery-Core. Brain volumes and white matter integrity were measured using standardized MRI protocols. Multivariable linear regression and mediation analyses were performed. Results: Among 2,662 participants, 50 (1.9%) had AF. Participants with AF showed lower total brain volume, regardless of tissue type, and reduced volumes in multiple brain regions. Overall cognitive function and specific domains (memory and executive function) were poorer in the AF group than in the normal group. AF remained significantly associated with lower total brain volume (p=0.005) and cognitive scores (p=0.037) after adjustment. Total brain volume partially mediated the AF-cognition association (p=0.007), accounting for 11% of the effect. Conclusions: AF is associated with brain atrophy and cognitive impairment, and brain structure partially mediates the association between AF and cognitive function. Our study findings suggest integrated cardiovascular and cognitive assessments in AF management.