BiomarkersHumans1,240 community-dwelling adults10 yearsCohort study

Three-region brain aging model better predicted death risk

A three-region model scored 0.81 versus 0.79 for a whole-brain model on a measure of how well it ranked death risk.

Graphical abstract from Cell Reports Medicine
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Graphical abstractLee et al.

Cell Reports Medicine

In an observational study, researchers followed 1,240 adults living in the community for 10 years, during which 120 died. They compared whole-brain age estimates with a model combining age estimates from three brain regions. The regional model predicted mortality better than the whole-brain approach.

An analysis of 513 blood proteins linked the regional signatures to activation of the complement system, a group of immune proteins, and disrupted adaptive immunity, the body's targeted immune response. Repeated brain scans in 444 participants also identified patterns of faster brain aging linked to declining thinking abilities.

Why it matters

Brain aging offers a marker of health across the body. The work addresses whether changes in particular brain regions can help identify broader vulnerabilities as people age.

Caveats

The study was observational, so the associations do not establish that brain aging or immune changes caused deaths, or confirm the proposed biological mechanisms.

The paper

Regional brain aging signatures predict mortality through neurovascular immune mechanisms

Pei-Lin Lee, Yi-Long Huang, Chih-Kuang Liang,
Show 4 more authorsWei-Ju Lee, Li-Ning Peng, Fei-Yuan Hsiao, Ching-Po Lin,
Liang-Kung Chen

National Yang Ming Chiao Tung University

Cell Reports Medicine · 7 Oct 2026

doi.org/10.1016/j.xcrm.2026.103096PubMed 42843341