Pulse pressure trajectories predict brain microstructure in community-dwelling older adults: Associations with executive function and modification by APOE

Abstract

Introduction: Effects of chronic arterial stiffness on brain aging remain unclear. We, therefore, examined whether long-term trajectories of pulse pressure (PP) predicted brain microstructure, microstructure mediated PP-executive function associations, and APOE genotype modified PP-microstructure associations. Methods: We examined associations of PP trajectories with brain microstructure measured using restriction spectrum imaging in 146 community-dwelling older adults, whether microstructure mediated PP trajectory-executive function associations, and whether PP-restriction spectrum imaging correlations were modified by APOE-ε4 status. Results: Participants with trajectories of high PP had lower restricted isotropic diffusion (RI) compared to those with low PP trajectories and PP-executive function associations were mediated by subcortical and white matter RI. High PP more strongly correlated with lower RI and higher hindered diffusion among APOE-ε4 carriers than non-carriers. Discussion: Prolonged elevated PP predicts microstructural abnormalities which may contribute to impaired executive function. APOE-ε4 carriers may be most vulnerable to the adverse effects of PP on brain microstructure.