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An empirical measure of resilience explains individual differences in the effect of tau pathology on memory change in aging

Nature Aging volume 3, pages 229–237 (2023)Cite this article

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Abstract

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.

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Fig. 1: CFA of two cognitive domains.
Fig. 2: PLS path model defining consolidated resilience.
Fig. 3: Consolidated resilience and ERC FTP interact to predict change in episodic memory.
Fig. 4: Interactive associations of consolidated resilience and global PiB DVR on cognitive domain scores.

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Data availability

Data used in this study (PET images, magnetic resonance images and cognitive data) will be shared by request from any qualified investigator subject to the negotiation of a data use agreement. Controlled access to human subjects data is required by the reviewing IRB and only deidentified data may be shared. Requests for data will be answered promptly and should be directed to W.J.J. (jagust@berkeley.edu).

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Acknowledgements

This research was supported by the National Institutes of Health grants R03-AG067033 (to T.M.H) and R01-AG034570 and R01-AG062542 (to W.J.J.). Support was also provided by the Tau Consortium (to W.J.J). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Avid Radiopharmaceuticals enabled the use of the [18 F] FTP tracer but did not provide direct funding and were not involved in data analysis or interpretation.

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Authors and Affiliations

  1. Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA

    Lindsey Dobyns, Kailin Zhuang, William J. Jagust & Theresa M. Harrison

  2. Lawrence Berkeley National Laboratory, Berkeley, CA, USA

    Suzanne L. Baker & William J. Jagust

  3. Department of Neurology, University of California, Davis, Sacramento, CA, USA

    Dan Mungas

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Contributions

T.M.H., D.M. and W.J.J. contributed to the conception and design of the study. L.D., K.Z., S.L.B. and T.M.H. contributed to the acquisition, curation and analysis of the data. L.D. and T.M.H. wrote the original manuscript draft. All authors contributed to drafting the final manuscript and figures.

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Correspondence to Theresa M. Harrison.

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Nature Aging thanks Eric Westman and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Numerical data used to run linear mixed effects models and create plots.

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Numerical data used to run linear mixed effects models and create plots.

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Dobyns, L., Zhuang, K., Baker, S.L. et al. An empirical measure of resilience explains individual differences in the effect of tau pathology on memory change in aging. Nat Aging 3, 229–237 (2023). https://doi.org/10.1038/s43587-022-00353-2

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