Chronological age accounts for much of the variance in structural brain measures, yet aging is spatially distributed, modality-dependent and often nonlinear, features that conventional T1-only brain-age models overlook. We introduce a population-calibrated, multimodal framework in 2,796 adults that integrates gray-matter volume with diffusion-derived metrics to fit linear and quadratic age-association profiles across cortical and subcortical regions. We define the Age of Structural Transition (AST) as the vertex of the preferred trajectory, marking maximal macrostructural or microstructural refinement before age-related reduction.
AST maps show early peaks in sensory-motor cortex and later peaks in association networks. Trajectory-based clustering uncovers distributed co-aging networks that group distant regions by shared multimodal trends rather than anatomy. A regionally stacked predictor improves age estimation (mean absolute error 3.45 years) and yields interpretable spatial importance maps.
Sliding-window analyses show that brain-age-gap associations with phenotypes are age-dependent, weak in younger adults and amplified later in life. We thank the participants, the Stauss center for computational neuroimaging and its staff as well as the Strauss Neuroplasticity Brain Bank (SNBB) at Tel Aviv University for recruitment and scanning infrastructure. G.K. gratefully acknowledges the support of a donation made in memory of Nissim Maman z"l.
This research is made possible through the support of BIRAX (The Britain-Israel Research and Academic Exchange, grant No. 43BX-PO) and the following funding partners: The European Research Council (ERC) under the European Union’s Horizon Europe research and innovation programme (grant agreement No. 101054909, COSMOS); the Rosetrees Trust; the Israel Science Foundation (ISF) (grant No. 803/24); and the Council for Higher Education in Israel through its competitive Data Science Centers program. Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel Gal Kepler, Shlomi Lifshits & Yaniv Assaf Strauss Center for Neuroimaging, Tel Aviv University, Tel Aviv, Israel School of Neurobiology, Biochemistry, and Biophysics, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel The authors declare no competing interests.
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