Interactive Effects of Pulse Pressure and Tau Imaging on Longitudinal Cognition

Abstract

Background: Studies have demonstrated that both tau and cardiovascular risk are associated with cognitive decline, but the possible synergistic effects of these pathologic markers remain unclear. Objective: To explore the interaction of AD biomarkers with a specific vascular risk marker (pulse pressure) on longitudinal cognition. Methods: Participants included 139 older adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Biomarkers of tau, amyloid-β (Aβ), and vascular risk (pulse pressure) were assessed. Neuropsychological assessment provided memory, language, and executive function domain composite scores at baseline and 1-year follow-up. Multiple linear regression examined interactive effects of pulse pressure with tau PET independent of Aβ PET and Aβ PET independent of tau PET on baseline and 1-year cognitive outcomes. Results: The interaction between pulse pressure and tau PET significantly predicted 1-year memory performance such that the combined effect of high pulse pressure and high tau PET levels was associated with lower memory at follow-up but not at baseline. In contrast, Aβ PET did not significantly interact with pulse pressure to predict baseline or 1-year outcomes in any cognitive domain. Main effects revealed a significant effect of tau PET on memory, and no significant effects of Aβ PET or pulse pressure on any cognitive domain. Conclusion: Results indicate that tau and an indirect marker of arterial stiffening (pulse pressure) may synergistically contribute to memory decline, whereas Aβ may have a lesser role in predicting cognitive progression. Tau and vascular pathology (particularly in combination) may represent valuable targets for interventions intended to slow cognitive decline.