Pulse Pressure, White Matter Hyperintensities, and Cognition: Mediating Effects Across the Adult Lifespan.

OBJECTIVES

To investigate whether pulse pressure or mean arterial pressure mediates the relationship between age and white matter hyperintensity load and to examine the mediating effect of white matter hyperintensities on cognition.

METHODS

Demographic information, blood pressure, current medication lists, and Montreal Cognitive Assessment scores for 231 stroke- and dementia-free adults were retrospectively obtained from the Aging Brain Cohort study. Total WMH load was determined from T2-FLAIR magnetic resonance scans using the TrUE-Net deep learning tool for white matter segmentation. In separate models, we used mediation analysis to assess whether pulse pressure or MAP mediates the relationship between age and total white matter hyperintensity load, controlling for cardiovascular confounds. We also assessed whether white matter hyperintensity load mediated the relationship between age and cognitive scores.

RESULTS

Pulse pressure, but not mean arterial pressure, significantly mediated the relationship between age and white matter hyperintensity load. White matter hyperintensity load partially mediated the relationship between age and Montreal Cognitive Assessment score.

INTERPRETATION: Our results indicate that pulse pressure, but not mean arterial pressure, is mechanistically associated with age-related accumulation of white matter hyperintensities, independent of other cardiovascular risk factors. White matter hyperintensity load was a mediator of cognitive scores across the adult lifespan. Effective management of pulse pressure may be especially important for maintenance of brain health and cognition.