Plasma biomarkers predict cognitive trajectories in an ethnoracially and clinically diverse cohort: Mediation with hippocampal volume
Shraddha Sapkota, Kelsey Erickson, Danielle Harvey, Sarah E. Tomaszewski‐Farias, John Olichney, David K. Johnson, Brittany N. Dugger, Dan Mungas, Evan Fletcher, Pauline Maillard, Sudha Seshadri, Claudia L. Satizábal, Tiffany F. Kautz, Danielle Parent, Russell P. Tracy, Izumi Maezawa, Lee‐Way Jin, Charles DeCarli
Abstract
Introduction: We examine whether the association between key plasma biomarkers (amyloid β [aβ] 42/40, total tau (t-tau), neurofilament light [NfL]) and cognitive trajectories (executive function [EF] and episodic memory [EM]) is mediated through neurodegeneration. Methods: = 473; baseline age range = 49-95 years, 60% women). We applied an accelerated longitudinal design to test latent growth models for EF and EM, and path and mediation analyses. Age was centered at 75 years, and all models were adjusted for sex, education, and ethnicity. Results: HV differentially mediated the association aβ 42/40 and NfL on EF and EM level and change. Hippocampal volume (HV) did not mediate the association between t-tau and cognitive performance. Discussion: Neurodegeneration as represented with HV selectively mediates the association between key non-invasive plasma biomarkers and cognitive trajectories in an ethnoracially and clinically diverse community-based sample.