{
  "abstract": "ObjectiveTo evaluate whether educational attainment and Alzheimer disease genetic risk were associated with GLP-1 receptor agonist initiation and dementia incidence and whether adjustment for these measured factors materially changed the estimated association between GLP-1 receptor agonist initiation and incident dementia among adults with type 2 diabetes.\n\nResearch Design and MethodsWe conducted an observational cohort study using linked electronic health record, survey, and genetic data from 14,364 All of Us Research Program participants with type 2 diabetes. We estimated associations of educational attainment and Alzheimer disease genetic risk with treatment initiation and incident dementia and compared GLP-1 receptor agonist initiators with initiators of non-sodium-glucose cotransporter 2 inhibitor second-line therapies, with a separate sodium-glucose cotransporter 2 inhibitor comparison. Models were estimated before and after additional adjustment for educational attainment, APOE {varepsilon}4, and non-APOE genetic risk.\n\nResultsAmong 14,364 participants (mean age, 60.2 years; 54.2% female), the mean follow-up duration was 4.3 years. The estimated hazard ratio for dementia comparing GLP-1 receptor agonist initiation with non-SGLT2 inhibitor second-line therapy was 0.85 (95% CI 0.64-1.12) before adjustment for education or Alzheimer disease genetic risk and 0.84 (95% CI 0.64-1.12) after adjustment for educational attainment, APOE {varepsilon}4, and non-APOE genetic risk.\n\nConclusionsAmong adults with type 2 diabetes, adjustment for measured educational attainment and Alzheimer disease genetic susceptibility produced little change in the estimated association between GLP-1 receptor agonist initiation and incident dementia. These findings do not exclude confounding by these factors in other populations or residual confounding from socioeconomic, clinical, behavioral, and health-care-related factors.\n\nHighlightsO_LIObservational studies have reported associations between GLP-1 receptor agonist use and lower dementia risk, but important social and genetic factors are often unavailable in electronic health record data. C_LIO_LIWe examined whether educational attainment and Alzheimer disease genetic susceptibility were associated with treatment initiation and dementia and whether adjustment for these factors changed GLP-1 receptor agonist-dementia estimates. C_LIO_LIAdding measured education and genetic susceptibility produced little change in the estimated conditional hazard ratios. C_LIO_LIThese results do not exclude residual confounding and should not be interpreted as evidence that GLP-1 receptor agonists prevent dementia. C_LI",
  "abstract_shown": true,
  "affiliations": [
    "Department of Epidemiology, Brown University, Providence, RI 02903"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "J. Wang"
    },
    {
      "name": "A. M. Pederson"
    },
    {
      "name": "M. D. Flanders"
    },
    {
      "name": "M. Choi"
    },
    {
      "name": "P. Buto"
    },
    {
      "name": "K. D. Sims"
    },
    {
      "name": "R. Chen"
    },
    {
      "name": "E. Couch"
    },
    {
      "name": "P. Gilsanz"
    },
    {
      "name": "K. N. Hayes"
    },
    {
      "name": "A. R. Zullo"
    },
    {
      "name": "A. Stokes"
    },
    {
      "name": "M. M. Glymour"
    },
    {
      "affs": [
        0
      ],
      "name": "S. F. Ackley"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bsrvhk9tntjxw.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.04.26362304",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.04.26362304v1.full",
  "id": "bsrvhk9tntjxw",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.04.26362304v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "neurology"
    ],
    [
      "openalex",
      "2712|Diabetes Treatment and Management"
    ]
  ],
  "openalex": "W7211942603",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.04.26362304v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bsrvhk9tntjxw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:00Z",
      "native_id": "10.64898/2026.09.04.26362304",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.04.26362304v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:neurology",
      "subfield": "neurology"
    }
  ],
  "title": "Education and Alzheimer Disease Genetic Risk in Associations of GLP-1 Receptor Agonists With Dementia Among Adults With Type 2 Diabetes",
  "title_text": "Education and Alzheimer Disease Genetic Risk in Associations of GLP-1 Receptor Agonists With Dementia Among Adults With Type 2 Diabetes",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:00Z",
  "url": "https://research.draconitic.com/paper/bsrvhk9tntjxw",
  "venue": "medRxiv",
  "versions": []
}