Accurately measuring resilience to preclinical Alzheimer's disease (AD) pathology is essential to understanding an important source of variability in cognitive aging. In a cohort of cognitively normal older adults (n = 123, age 76.75 ± 6.15 yr), we built a multifactorial measure of resilience which moderated the effect of AD pathology on longitudinal cognitive change. Linear residuals-based measures of resilience, along with other proxy measures (education and vocabulary), were entered into a hierarchical partial least-squares path model defining a putative consolidated resilience latent factor (model goodness of fit = 0.77). In a set of validation analyses using linear mixed models predicting longitudinal cognitive change, there was a significant three-way interaction among consolidated resilience, tau and time on episodic memory change (P = 0.001) such that higher resilience blunted the effect of tau pathology on episodic memory decline. Interactions between consolidated resilience and amyloid pathology on non-memory cognition decline suggested that resilience moderates pathology-specific effects on different cognitive domains.
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.