{
  "abstract": "Background\n\nApolipoprotein E ε4 (APOE-ε4), the strongest genetic risk factor for late-onset Alzheimer disease (AD), is associated with early neuromotor vulnerability that may precede measurable cognitive decline. Because speech integrates fine neuromotor processes, acoustic analysis could offer a sensitive, noninvasive marker of preclinical effects.Objective\n\nThis study aims to determine if speech acoustics distinguish cognitively normal APOE-ε4 carriers from noncarriers, and to assess which speech tasks provide optimal classification performance.Methods\n\nIn this cross-sectional observational study, 80 cognitively normal adults aged 41 to 89 years (22 APOE-ε4 carriers and 58 noncarriers) completed sustained phonation, oral diadochokinetic syllable repetition, passage reading, and spontaneous-speech tasks. Speech samples were collected remotely using participants' personal devices and processed to extract 88 acoustic features from the extended Geneva Minimalistic Acoustic Parameter Set. Task-specific random forest classifiers were developed to distinguish APOE-ε4 carriers from noncarriers. A genetic algorithm was used to select informative features, and model performance was evaluated using leave-one-participant-out cross-validation. Performance metrics included balanced accuracy, accuracy, precision, sensitivity, specificity, F₁-score, and receiver operating characteristic area under the curve (ROC-AUC).Results\n\nSpontaneous speech produced the strongest classification performance, with balanced accuracy of 0.84, accuracy of 0.89, sensitivity of 0.73, specificity of 0.95, F₁-score of 0.78, and ROC-AUC of 0.75. Performance was lower for sustained phonation (F₁-score=0.69), diadochokinetic syllable repetition (F₁-score =0.70 for /ba/ and 0.64 for /pa/), and passage reading (F₁-score=0.61). Combining recordings across tasks reduced performance (F₁-score=0.53), indicating that task-specific acoustic patterns were more informative than pooled data.Conclusions\n\nAutomated analysis of task-specific acoustic speech features, particularly spontaneous speech, internally distinguished cognitively normal APOE-ε4 carriers from noncarriers. These findings support further validation of speech acoustics as a low-burden digital biomarker of preclinical AD risk and suggest that spontaneous-speech tasks may be especially well suited for future remote and longitudinal assessment.",
  "abstract_shown": true,
  "affiliations": [
    "Mass General Brigham University of Health Professions, Charlestown, MA, United States.",
    "Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States.",
    "Speech and Hearing Bioscience and Technology, Harvard University, Boston, MA, United States.",
    "Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.",
    "Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Jamaica Plain, MA, United States.",
    "Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Maryam Tavakoli",
      "orcid": "0009-0004-8085-6227"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mehrdad Dadgostar",
      "orcid": "0000-0002-3238-1261"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Jordan R Green",
      "orcid": "0000-0002-1464-1373"
    },
    {
      "affs": [
        1,
        3,
        4
      ],
      "name": "David H Salat",
      "orcid": "0000-0002-2246-9657"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Steven E Arnold",
      "orcid": "0000-0002-9487-415X"
    },
    {
      "affs": [
        0
      ],
      "name": "Kathryn P Connaghan",
      "orcid": "0000-0003-0849-1441"
    },
    {
      "affs": [
        0
      ],
      "name": "Brian Richburg",
      "orcid": "0000-0002-9191-2202"
    },
    {
      "affs": [
        0
      ],
      "name": "Nelson V Barnett",
      "orcid": "0009-0000-0363-1244"
    },
    {
      "affs": [
        0
      ],
      "name": "Mariam Tkeshelashvili",
      "orcid": "0009-0001-4393-0473"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "Marziye Eshghi",
      "orcid": "0000-0003-1270-6521"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7cf1j0nz7n951.bib",
  "cited_by": 0,
  "doi": "10.2196/89830",
  "fulltext_url": "https://europepmc.org/articles/PMC13691465",
  "id": "7cf1j0nz7n951",
  "issns": [
    "2561-326X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42849896",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2738|Dementia and Cognitive Impairment Research"
    ]
  ],
  "openalex": "W7221045225",
  "pdf_url": "https://europepmc.org/articles/PMC13691465?pdf=render",
  "pmcid": "PMC13691465",
  "pmid": "42849896",
  "published": "2026-10-08",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7cf1j0nz7n951.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:02Z",
      "native_id": "MED:42849896",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42849896"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2738|Dementia and Cognitive Impairment Research",
      "subfield": "psychiatry"
    }
  ],
  "title": "Remote Identification of APOE-ε4 Carrier Status in Cognitively Normal Adults via Speech Acoustics: Cross-Sectional Observational Study.",
  "title_text": "Remote Identification of APOE-ε4 Carrier Status in Cognitively Normal Adults via Speech Acoustics: Cross-Sectional Observational Study.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:02Z",
  "url": "https://research.draconitic.com/paper/7cf1j0nz7n951",
  "venue": "JMIR formative research",
  "versions": []
}