{
  "abstract": "BackgroundStudies indicate that the apolipoprotein E (APOE) {varepsilon}4 allele is the strongest genetic risk factor for Alzheimers disease (AD), and individuals with this allele are at increased risk of developing AD, there remains debate regarding whether APOE {varepsilon}4 carriers experience more rapid cognitive decline over time compared to non-carriers. This study assessed this question using linear mixed-effects models applied to the placebo arm of EXPEDITION 1, a phase 3 clinical trial evaluating solanezumab in patients with mild-to-moderate Alzheimers disease.\n\nMethodsIn this study we utilized data from 370 participants in the placebo group of the EXPEDITION 1 trial. After excluding 27 participants with undefined APOE genotype, all models and analyses were applied to the remaining 343 participants (686 ADAS-Cog14 observations) to determine whether APOE {varepsilon}4 carriers exhibit a faster rate of decline over the 80-week follow-up period. Five nested linear mixed-effects models with a participant-specific random intercept were fitted, and also a complementary change-score analysis was done.\n\nResultsOver 80 weeks, ADAS-Cog14 worsened by an average of 7.01 points. Carriers did not decline faster than non-carriers (additional decline 1.31 points; 95% CI -1.22 to 3.83; p = 0.310), and the change-score analysis showed the same pattern. Carriers had worse ADAS-Cog14 scores overall, but this difference was no longer significant after adjustment for baseline CDR-SB.\n\nConclusionIn this cohort, APOE {varepsilon}4 carrier status was related to disease severity at baseline rather than to the rate of cognitive decline over 80 weeks.",
  "abstract_shown": true,
  "affiliations": [
    "Faculty of Agricultural and Food Sciences, University of Milan, Milan, Italy"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "A. Heidari"
    },
    {
      "name": "M. Aghajani"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/57rx830kcfwxa.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.27.26364131",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.27.26364131v1.full",
  "id": "57rx830kcfwxa",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.27.26364131v1",
  "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",
      "2738|Dementia and Cognitive Impairment Research"
    ]
  ],
  "openalex": "W7214804398",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.27.26364131v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-27",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/57rx830kcfwxa.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:41Z",
      "native_id": "10.64898/2026.09.27.26364131",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.27.26364131v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:neurology",
      "subfield": "neurology"
    }
  ],
  "title": "APOE ε4 Carrier Status and Cognitive Decline in Mild-to-Moderate Alzheimer's Disease: A Linear Mixed-Effects Analysis of the Placebo Arm of EXPEDITION 1",
  "title_text": "APOE ε4 Carrier Status and Cognitive Decline in Mild-to-Moderate Alzheimer's Disease: A Linear Mixed-Effects Analysis of the Placebo Arm of EXPEDITION 1",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:41Z",
  "url": "https://research.draconitic.com/paper/57rx830kcfwxa",
  "venue": "medRxiv",
  "versions": []
}