{
  "abstract": "INTRODUCTIONMultimodal lifestyle interventions can delay or slow Alzheimers disease (AD) in at-risk older adults, and plasma pTau217, a blood-based biomarker, now enables scalable AD risk stratification. Populationlevel screening integrating genetic, biomarker, and lifestyle risk factors, alongside attitudes toward risk disclosure, remains understudied. This pilot assessed dementia-risk attitudes before and after disclosure and tested a personalized, data-driven multimodal coaching intervention in a high-risk Alabama population.\n\nMETHODSCognitively normal adults aged 65-75 with a first-degree relative affected by AD/dementia were recruited in north Alabama and screened using the Montreal Cognitive Assessment, family history, APOE genotyping, non-APOE AD polygenic risk score, and plasma pTau217. A composite rubric classified high-risk status (score >5 and/or pTau217 >0.18 pg/mL); high-risk participants received results disclosure and a 6-month personalized intervention (dietitian-led coaching, cognitive training, activity tracking). Pre- and postdisclosure attitudes, distress (REVEAL IGT-AD scale), and biomarker/cognitive measures were assessed.\n\nRESULTSOf 138 screened participants, 52 (37.7%) were high-risk, most (69.2%) by pTau217 alone. Before disclosure, subjective dementia-risk perception correlated with objective risk score. Scores consistent with post-disclosure clinically significant distress occurred in 28% of survey respondents in at least one timepoint but was often (50%) observed with pre-existing anxiety/depression. Over 6 months, MoCA scores and lifestyle risk indices were unchanged, pTau217 continued rising but at a slowed rate compared to between screening and the beginning of the lifestyle intervention, and self-reported worry and perceived dementia risk decreased significantly.\n\nDISCUSSIONA genomics- and biomarker-informed screening and coaching model is feasible in a high-risk cohort in the deep south, with manageable distress and improved attitudes despite limited short-term biological change. Findings support larger, longer, and more diverse trials validating this approach for AD screening.",
  "abstract_shown": true,
  "affiliations": [
    "HudsonAlpha Institute for Biotechnology"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 29,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "M. Cochran"
    },
    {
      "name": "J. Pugh"
    },
    {
      "name": "T. Coleman"
    },
    {
      "name": "W. Kelley"
    },
    {
      "name": "P. Jamieson"
    },
    {
      "name": "E. Dunne"
    },
    {
      "name": "P. Smith"
    },
    {
      "name": "J. Chasteen"
    },
    {
      "name": "M. Jones"
    },
    {
      "name": "J. Turner"
    },
    {
      "name": "H. Hurns"
    },
    {
      "name": "G. Geissler"
    },
    {
      "name": "M. Brunkow"
    },
    {
      "name": "S. Q. Johnston"
    },
    {
      "name": "K. Metzger"
    },
    {
      "name": "L. Seyfarth"
    },
    {
      "name": "J. Taylor"
    },
    {
      "name": "E. Shields"
    },
    {
      "name": "W. Herrington"
    },
    {
      "name": "W. Schroer"
    },
    {
      "name": "S. Newberry"
    },
    {
      "name": "A. Hurst"
    },
    {
      "name": "J. Yurkovich"
    },
    {
      "name": "N. Lamb"
    },
    {
      "name": "L. Hood"
    },
    {
      "name": "S. Evans"
    },
    {
      "name": "F. P. Behn"
    },
    {
      "name": "J. Lovejoy"
    },
    {
      "affs": [
        0
      ],
      "name": "J. N. Cochran"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8ym2hhcd66d6s.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.19.26363495",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.19.26363495v1.full",
  "id": "8ym2hhcd66d6s",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.19.26363495v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "neurology"
    ],
    [
      "openalex",
      "2738|Dementia and Cognitive Impairment Research"
    ]
  ],
  "openalex": "W7213899639",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.19.26363495v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/8ym2hhcd66d6s.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:05Z",
      "native_id": "10.64898/2026.09.19.26363495",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.19.26363495v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:neurology",
      "subfield": "neurology"
    }
  ],
  "title": "Clinical and attitudinal outcomes of a personalized, multimodal lifestyle intervention for Alzheimer's disease prevention in high-risk, cognitively normal older adults in north Alabama: A pilot study",
  "title_text": "Clinical and attitudinal outcomes of a personalized, multimodal lifestyle intervention for Alzheimer's disease prevention in high-risk, cognitively normal older adults in north Alabama: A pilot study",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:05Z",
  "url": "https://research.draconitic.com/paper/8ym2hhcd66d6s",
  "venue": "medRxiv",
  "versions": []
}