{
  "abstract": "Objective Anxiety is a prominent neuropsychiatric symptom in preclinical Alzheimer's disease (AD), but the neural circuitry linking anxiety and AD remains uncharacterized. We assessed whether anxiety in preclinical AD is independently associated with AD-related neurodegeneration and localizes to a common anxiety network. Methods In cognitively unimpaired (CU) older adults with 3T MRI and amyloid-beta PET (N=1,775), we examined whether an established AD-related atrophy network is associated with anxiety (STAI-6). Then, using Atrophy Network Mapping (ANM), which maps individual cortical atrophy patterns onto a normative functional connectome (N=1000), we derived an anxiety network. We tested its 1) spatial convergence with the AD network and with a causal anxiety network derived from lesion and neuromodulation data, 2) specificity relative to depression, 3) generalizability in samples from independent cohorts with AD and Parkinson's disease (total n=878), and 4) association with longitudinal outcomes. Results In CU older adults, greater AD-network atrophy was associated with higher anxiety, independent of depression, cognition, cortical atrophy, and amyloid burden. Anxiety localized to a network closely resembling the AD network (r=0.74, p=0.04) and the causal anxiety network (r=0.72, p=0.02). This convergence extended across the AD continuum and to the Parkinson's disease cohort and was specific to anxiety relative to depression. Greater anxiety-network atrophy was associated with cognitive decline over 4.6 years. Conclusion Anxiety localizes to a brain circuit resembling the AD-related atrophy network, is consistent across the AD continuum and may extend beyond AD. These findings support anxiety as an independent marker of early AD-related neurodegeneration.",
  "abstract_shown": true,
  "affiliations": [
    "Brigham and Women's Hospital"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "S. Lee"
    },
    {
      "name": "J. Ha"
    },
    {
      "name": "A. H. Garimella"
    },
    {
      "name": "S. R. Baratono"
    },
    {
      "name": "G. T. Burt"
    },
    {
      "name": "H. T. Karim"
    },
    {
      "name": "C. Andreescu"
    },
    {
      "name": "R. A. Sperling"
    },
    {
      "name": "N. J. Donovan"
    },
    {
      "name": "M. D. Fox"
    },
    {
      "name": "S. H. Siddiqi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6b0g9k1ydcejh.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.24.761536",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.24.761536v1.full",
  "id": "6b0g9k1ydcejh",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.24.761536v1",
  "language": "en",
  "licence": "CC0-1.0",
  "licence_label": "CC0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/publicdomain/zero/1.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2738|Dementia and Cognitive Impairment Research"
    ]
  ],
  "openalex": "W7223652078",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.24.761536v1.full.pdf",
  "pmcid": "PMC13733806",
  "pmid": "42990252",
  "published": "2026-10-24",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/6b0g9k1ydcejh.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:39Z",
      "native_id": "10.64898/2026.10.24.761536",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.24.761536v1"
    },
    {
      "first_seen": "2026-11-08T12:23:30Z",
      "native_id": "PMC13733806",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.24.761536"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Network Localization of Anxiety as an Early Manifestation of Alzheimer's Disease-related Neurodegeneration",
  "title_text": "Network Localization of Anxiety as an Early Manifestation of Alzheimer's Disease-related Neurodegeneration",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:30Z",
  "url": "https://research.draconitic.com/paper/6b0g9k1ydcejh",
  "venue": "bioRxiv",
  "versions": []
}