{
  "abstract": "Brain aging provides an integrative marker of systemic health, but whether regional patterns outperform whole-brain approaches remains unknown. Here, we show that regional brain age signatures achieve superior mortality prediction through identifiable neurovascular-immune mechanisms in 1,240 community-dwelling adults followed for 10 years (120 deaths). While global brain age independently predicts mortality (hazard ratio [HR], 1.044 per year), a data-driven three-region model combining the left precentral gyrus, left parahippocampal gyrus, and right cerebellum achieves superior discrimination (C-index, 0.81 vs. 0.79, p = 0.032). Integration with plasma proteomics (513 proteins) reveals complement activation and adaptive immune dysregulation as convergent mechanisms. Region-specific vulnerabilities emerge: microvascular dysfunction in the motor cortex, proteostasis failure in the medial temporal structures, and iron dysregulation in the cerebellum. Longitudinal imaging (n = 444) identifies accelerated brain aging phenotypes predicting cognitive decline (HR, 1.558; p = 0.042). These findings establish regional neuroimaging-proteomic integration as a precision strategy linking network-specific vulnerabilities to systemic immune processes.",
  "abstract_shown": true,
  "affiliations": [
    "Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan",
    "Center for Geriatrics and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan",
    "Division of Neurology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan",
    "Department of Geriatric Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan",
    "Department of Family Medicine, Taipei Veterans General Hospital Yuanshan Branch, Yilan 26444, Taiwan",
    "Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei 11217, Taiwan",
    "Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei 10051, Taiwan",
    "School of Pharmacy, College of Medicine, National Taiwan University, Taipei 10051, Taiwan",
    "Department of Pharmacy, National Taiwan University Hospital, Taipei 100225, Taiwan",
    "Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan",
    "Brain Research Center, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan",
    "Department of Education and Research, Taipei City Hospital, Taipei 103212, Taiwan",
    "Taipei Municipal Gan-Dau Hospital (managed by Taipei Veterans General Hospital), Taipei 112020, Taiwan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Pei-Lin Lee"
    },
    {
      "affs": [
        0
      ],
      "name": "Yi-Long Huang"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Chih-Kuang Liang"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Wei-Ju Lee"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Li-Ning Peng"
    },
    {
      "affs": [
        6,
        7,
        8
      ],
      "name": "Fei-Yuan Hsiao"
    },
    {
      "affs": [
        9,
        10,
        11
      ],
      "name": "Ching-Po Lin"
    },
    {
      "affs": [
        0,
        5,
        12
      ],
      "name": "Liang-Kung Chen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a8dcye7fh5r77.bib",
  "cited_by": 0,
  "doi": "10.1016/j.xcrm.2026.103096",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710373/",
  "id": "a8dcye7fh5r77",
  "issns": [
    "2666-3791"
  ],
  "landing_url": "https://doi.org/10.1016/j.xcrm.2026.103096",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2738|Dementia and Cognitive Impairment Research"
    ]
  ],
  "openalex": "W7220845557",
  "pdf_url": null,
  "pmcid": "PMC13710373",
  "pmid": "42843341",
  "published": "2026-10-07",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/a8dcye7fh5r77.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:21Z",
      "native_id": "PMC13710373",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.xcrm.2026.103096"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2738|Dementia and Cognitive Impairment Research",
      "subfield": "psychiatry"
    }
  ],
  "title": "Regional brain aging signatures predict mortality through neurovascular immune mechanisms",
  "title_text": "Regional brain aging signatures predict mortality through neurovascular immune mechanisms",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:21Z",
  "url": "https://research.draconitic.com/paper/a8dcye7fh5r77",
  "venue": "Cell Reports Medicine",
  "versions": []
}