{
  "abstract": "Importance: Concern that anticholinergic medications for overactive bladder (OAB) are associated with increased dementia risk has encouraged a shift toward β3 adrenergic agonists, which are presumed cognitively safer. Whether this presumption is justified is uncertain.\n\nObjective: To compare the risk of incident dementia among adults initiating high-risk anticholinergic, low-risk anticholinergic, or β3 agonist therapy for OAB and to evaluate the association of treatment duration with risk.\n\nDesign, Setting, and Participants: This retrospective cohort study used Epic Cosmos electronic health record data from 2012 to 2025. Adults aged 40 to 90 years newly treated for OAB within 1 year of diagnosis without preexisting dementia were included.\n\nExposures: First prescribed medication class: high-risk anticholinergics (oxybutynin, tolterodine, or solifenacin), low-risk anticholinergics (darifenacin, trospium, or fesoterodine), or β3 agonists (mirabegron or vibegron).\n\nMain Outcomes and Measures: Incident dementia by diagnosis code or dementia-specific medication. Inverse probability of treatment weighting (IPTW) and Cox proportional hazards models were used, with analyses stratified by age and sex and an exploratory landmark duration-response analysis.\n\nResults: Among 830 393 patients (585 198 female [70.5%]; median [IQR] age, 67 [57-76] years), incident dementia occurred in 65 134 patients, with a median (IQR) follow-up ranging from 1046 (571-1809) days for β3 agonists to 1568 (857-2614) days for high-risk anticholinergics. After IPTW, high-risk anticholinergics were associated with a lower hazard of dementia than β3 agonists (hazard ratio [HR], 0.90; 95% CI, 0.87-0.93) and low-risk anticholinergics (HR, 0.93; 95% CI, 0.90-0.96); low-risk anticholinergics did not differ from β3 agonists (HR, 0.97; 95% CI, 0.93-1.01). Weighted 10-year dementia risk was highest for β3 agonists (20.0%; 95% CI, 18.8%-21.2%) and lowest for high-risk anticholinergics (18.1%; 95% CI, 17.9%-18.3%). E-values of 1.29 (high-risk anticholinergics vs β3 agonists) and 1.20 (high-risk vs low-risk anticholinergics) suggested that observed differences could be explained by a modest amount of unmeasured confounding. Longer anticholinergic duration was not associated with increased risk.\n\nConclusions and Relevance: In this cohort study of patients undergoing treatment for OAB, β3 agonists were not associated with a lower dementia incidence compared with anticholinergics. These findings suggest that previously reported increases in risk may reflect residual confounding rather than a pharmacological effect.",
  "abstract_shown": true,
  "affiliations": [
    "University Hospitals Cleveland Medical Center Urology Institute, Cleveland, Ohio",
    "Department of Statistics and Data Science, Oberlin College and Conservatory, Oberlin, Ohio"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "David Sheyn"
    },
    {
      "affs": [
        0
      ],
      "name": "Stephen Rhodes"
    },
    {
      "affs": [
        1
      ],
      "name": "Zeinab Mohamed"
    },
    {
      "affs": [
        0
      ],
      "name": "Adonis Hijaz"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cx8wpht8w36z8.bib",
  "cited_by": 0,
  "doi": "10.1001/jamanetworkopen.2026.42026",
  "fulltext_url": null,
  "id": "cx8wpht8w36z8",
  "issns": [
    "2574-3805"
  ],
  "landing_url": "https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2856326",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-06",
  "publisher": "American Medical Association (AMA)",
  "ris": "https://research.draconitic.com/paper/cx8wpht8w36z8.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T00:21:20Z",
      "native_id": "10.1001/jamanetworkopen.2026.42026",
      "source": "crossref",
      "url": "https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2856326"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:2574-3805",
      "subfield": "general"
    }
  ],
  "title": "Drug Therapies and Incidence of Dementia Among Adults With Overactive Bladder",
  "title_text": "Drug Therapies and Incidence of Dementia Among Adults With Overactive Bladder",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T00:22:58Z",
  "url": "https://research.draconitic.com/paper/cx8wpht8w36z8",
  "venue": "JAMA Network Open",
  "versions": []
}