UC San Diego

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.