Structural and load-dependent arterial stiffness are differentially associated with cognition or biomarkers of Alzheimer's disease and related dementias: The healthy brain study

BackgroundArterial stiffness is an emerging risk factor for Alzheimer's disease (AD) and related dementias (ADRD) and is assessed by measuring pulse wave velocity (PWV). Recent mathematical modeling has allowed for the delineation of arterial stiffness caused by structural remodeling (S) and blood pressure, termed "load-dependent" stiffening (LD). While we recently demonstrated that S-PWV and LD-PWV are differentially associated with risk for cognitive decline and AD/ADRD brain imaging biomarkers, the associations between paired measures of S-PWV and LD-PWV with cognitive function, AD/ADRD brain imaging biomarkers, and plasma AD biomarkers have not been assessed.ObjectiveTo conduct a comprehensive analysis combining cross-sectional data from the Wake Forest Alzheimer's Disease Research Center. We hypothesized that higher S-PWV would be associated with worse cognitive function. We also hypothesized that S-PWV and LD-PWV would be differentially associated with brain imaging biomarkers of ADRD and plasma AD biomarkers.MethodsMultivariable linear regression models were used to relate S-PWV and LD-PWV to all outcomes.ResultsAs hypothesized, higher S-PWV, but not LD-PWV, was associated with lower global cognitive function. Higher S-PWV and LD-PWV were differentially associated with AD/ADRD brain MRI biomarkers. We did not observe any significant associations with plasma or PET AD biomarkers in this cohort.ConclusionsS-PWV was associated with lower cognition, while S-PWV and LD-PWV were differentially associated with brain MRI biomarkers. Interventions specifically targeting arterial stiffness may preserve cognition and brain health in AD/ADRD.