Abstract
Brain maintenance may help explain why some individuals remain cognitively resilient despite aging, but its biological basis is not well understood. Here, we show that brain maintenance can be quantified from the relationship between brain structure and function. Using structural MRI and resting-state functional MRI from 1280 older adults, we built a model based on young adults to estimate the functional capacity supported by preserved brain structure, and defined brain maintenance as the difference between predicted and observed function. Brain maintenance was most evident in prefrontal, cingulate, and precuneus regions and was enriched in higher-order functional networks. Higher brain maintenance was associated with slower cognitive decline, lower amyloid-β burden, and domain-specific variation in memory, attention, and processing speed. These findings provide a biologically grounded marker of resilience in healthy and pathological aging.
Similar content being viewed by others
Acknowledgements
We thank all participants, their relatives, and our community partners for their support and participation in this study. This work was supported by Brain Science and Brain-like Intelligence Technology - National Science and Technology Major Project (2022ZD0211600, ZZJ), the State Key Program of the National Natural Science Foundation of China (82130118, ZZJ), the Beijing Natural Science Foundation (5262011, LX), Open Research Fund of the State Key Laboratory of Cognitive Neuroscience and Learning (CNLYB2402, LX), and the Tang Scholar Program (LX).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Source data
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
About this article
Cite this article
Li, Y., Zhang, X., Li, X. et al. Brain maintenance biomarkers from structural and functional interactions in aging and neurodegeneration. Nat Commun (2026). https://doi.org/10.1038/s41467-026-73071-7
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41467-026-73071-7
