RESUMO
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-ß (Aß), 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 Aß PET and Aß 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, Aß 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 Aß 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 Aß 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.
