Interactive Effects of Pulse Pressure and Tau Imaging on Longitudinal Cognition

Article type: Research Article

Authors: Weigand, Alexandra J.^a | Macomber, Alyssa J.^b | Walker, Kayla S.^c | Edwards, Lauren^a | Thomas, Kelsey R.^{b; d} | Bangen, Katherine J.^{b; d} | Nation, Daniel A.^e | Bondi, Mark W.^{b; d; *} | Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA | [b] Department of Psychiatry, University of California San Diego, La Jolla, CA, USA | [c] San Diego State University, San Diego, CA, USA | [d] VA San Diego Healthcare System, San Diego, CA, USA | [e] University of California Irvine, Irvine, CA, USA

Correspondence: [*] Correspondence to: Mark W. Bondi, PhD, ABPP-CN, VA San Diego Healthcare System (116B), 3350 La Jolla Village Drive, San Diego, CA 92161, USA. Tel.: +1 858 646 2809; E-mail: [email protected].

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (https://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: https://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

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.

Keywords: Amyloid PET, cardiovascular risk, cognition, executive function, memory, pulse pressure, tau PET

DOI: 10.3233/JAD-220026

Journal: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 633-640, 2022