{
  "abstract": "Identifying the neurobiological basis of cognitive vulnerability is essential for preventing Alzheimer’s disease (AD). We derived the Alzheimer’s Resilience-Vulnerability Connectome (ARC) by contrasting SuperAgers (SA), an extreme phenotype of preserved late-life memory, with AD using resting-state fMRI. ARC distinguished SA from AD in a discovery cohort (N = 290; AUC = 0.85) and replicated independently (N = 143), involving prefrontal, temporal, and insular networks and associating with brain age. Applied to cognitively unimpaired adults (discovery: N = 818; replication: N = 497), ARC-based subtyping revealed SA-like and AD-like subgroups with comparable baseline cognition but divergent longitudinal trajectories. AD-like individuals exhibited faster cognitive decline, greater amyloid-β accumulation, and higher AD conversion risk. Exploratory GWAS nominated CLYBL and FRMD6 as candidate novel loci associated with the subtype difference. These findings suggest that ARC captures a continuous connectomic dimension of cognitive aging spanning SA, cognitively typical aging, and AD, highlighting the potential of functional connectomic variation for early risk stratification in AD.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.",
    "Department of Bioengineering, Lehigh University, Bethlehem, PA, USA.",
    "Goodman-Luskin Microbiome Center, Vache and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.",
    "Center for Neuroscience Research, Children’s National Hospital, Washington, DC, USA.",
    "Center for Psychedelic Research and Therapy, Department of Psychiatry and Behavioral Sciences, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.",
    "Department of Psychology, Lehigh University, Bethlehem, PA, USA.",
    "Penn State College of Medicine, Hershey, PA, USA.",
    "Department of Psychiatry, New York University Grossman School of Medicine, New York, NY, USA.",
    "Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.",
    "Stanford Institute for Human-Centered Artificial Intelligence, Stanford, CA, USA."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Kanhao Zhao",
      "orcid": "0000-0002-2955-0917"
    },
    {
      "affs": [
        3
      ],
      "name": "Hua Xie",
      "orcid": "0000-0003-3462-0147"
    },
    {
      "affs": [
        4
      ],
      "name": "Gregory A. Fonzo",
      "orcid": "0000-0002-0213-1034"
    },
    {
      "affs": [
        5
      ],
      "name": "Nancy B. Carlisle",
      "orcid": "0000-0002-9161-8556"
    },
    {
      "affs": [
        6
      ],
      "name": "Tovia Jacobs"
    },
    {
      "affs": [
        7
      ],
      "name": "Ricardo S. Osorio"
    },
    {
      "affs": [
        2
      ],
      "name": "Arpana Church",
      "orcid": "0000-0002-1669-9624"
    },
    {
      "affs": [
        0,
        8,
        9
      ],
      "name": "Feng Vankee Lin",
      "orcid": "0000-0003-1945-0362"
    },
    {
      "affs": [
        0,
        8,
        9
      ],
      "name": "Yu Zhang",
      "orcid": "0000-0003-4087-6544"
    },
    {
      "name": "Alzheimer’s Disease Neuroimaging Initiative"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4221frynfvht0.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aed9351",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13733855/",
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    "2375-2548"
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  "landing_url": "https://www.science.org/doi/abs/10.1126/sciadv.aed9351",
  "language": "en",
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  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Health and Medicine"
    ],
    [
      "heading",
      "Neuroscience"
    ],
    [
      "heading",
      "Research Article"
    ],
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      "heading",
      "SciAdv r-articles"
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  "openalex": null,
  "pdf_url": null,
  "pmcid": "PMC13733855",
  "pmid": "42981415",
  "published": "2026-11-04",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/4221frynfvht0.ris",
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  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Neuroscience",
      "subfield": "neuroscience"
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  ],
  "title": "A functional connectome identifies vulnerability to cognitive decline and Alzheimer’s disease progression",
  "title_text": "A functional connectome identifies vulnerability to cognitive decline and Alzheimer’s disease progression",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:23:32Z",
  "url": "https://research.draconitic.com/paper/4221frynfvht0",
  "venue": "Science Advances",
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}