{
  "abstract": "ObjectiveEffective strategies to prevent Alzheimers disease and related dementias (ADRD) are limited. Implementing our Medication-Wide Association Study (MWAS+), we highlighted varenicline as a candidate. This study evaluated the association between varenicline use and risk of ADRD relative to nicotine replacement therapy (NRT).\n\nMethodsUsing the All of Us Research Database, we identified adults aged 50 years or older with available lifestyle survey responses regarding tobacco use history who initiated smoking cessation therapy with either varenicline or NRT between 2006 and 2023. We limited our cohort to incident monotherapy users and designated the index date as the first prescription. Individuals with baseline ADRD or no follow-up were excluded. Baseline characteristics included demographics, comorbidities, BMI, and prior medication exposures. Outcomes were incident ADRD and a composite outcome of ADRD or death.\n\nFindingsThe cohort consisted of 9,584 individuals (1,801 varenicline users and 7,783 NRT users). After propensity score matching, there were 1,758 individuals in each group with balanced baseline characteristics. Varenicline use was associated with a reduced risk of ADRD (HR 0.516, 95% CI: 0.353-0.754) and the composite outcome ADRD or death (HR 0.657, 95% CI: 0.501-0.861). Kaplan-Meier curves also demonstrated vareniclines sustained benefits through the study period.\n\nImplicationsVarenicline use is associated with a lower risk of ADRD among older adults receiving smoking cessation therapy. Further investigation of varenicline as a potential strategy for ADRD prevention is warranted. These findings underscored the value of explainable AI-guided approaches to drug repurposing.\n\nHighlightO_LIArtificial Intelligence (AI) Medication-Wide Association Study (MWAS+) identified varenicline as candidate for ADRD prevention. C_LIO_LIVarenicline linked to lower ADRD risk vs NRT in propensity score matched cohort. C_LIO_LIConsistent results for ADRD and composite outcome ADRD or death. C_LI",
  "abstract_shown": true,
  "affiliations": [
    "Washington DC VA Medical Center, Washington, DC, United States; George Washington University, Washington, DC, United States"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "name": "P. Ma"
    },
    {
      "name": "J. Zhou"
    },
    {
      "name": "Y. Cheng"
    },
    {
      "name": "J. E. McGeary"
    },
    {
      "name": "T. H. Taveira"
    },
    {
      "name": "A. Ahmed"
    },
    {
      "name": "W.-C. Wu"
    },
    {
      "name": "E. Zamrini"
    },
    {
      "name": "B. N. Dugger"
    },
    {
      "name": "L. N. C. Sevilla"
    },
    {
      "name": "J. A. Nations"
    },
    {
      "name": "Y. Shao"
    },
    {
      "name": "Y. Yin"
    },
    {
      "name": "D. W. Tsuang"
    },
    {
      "name": "M. W. Logue"
    },
    {
      "name": "S. Ayandeh"
    },
    {
      "name": "C. Faselis"
    },
    {
      "name": "S. J. Nelson"
    },
    {
      "affs": [
        0
      ],
      "name": "Q. Zeng-Treitler"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4f4bv5cq2axes.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.17.26363232",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.17.26363232v1.full",
  "id": "4f4bv5cq2axes",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.17.26363232v1",
  "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",
      "pharmacology and therapeutics"
    ],
    [
      "openalex",
      "2737|Smoking Behavior and Cessation"
    ]
  ],
  "openalex": "W7213749940",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.17.26363232v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4f4bv5cq2axes.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:56Z",
      "native_id": "10.64898/2026.09.17.26363232",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.17.26363232v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:pharmacology and therapeutics",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Varenicline as a Repurposable Drug Candidate for ADRD Prevention",
  "title_text": "Varenicline as a Repurposable Drug Candidate for ADRD Prevention",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:56Z",
  "url": "https://research.draconitic.com/paper/4f4bv5cq2axes",
  "venue": "medRxiv",
  "versions": []
}