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Detecting Preclinical Alzheimer’s Disease Risk in Cognitively Normal Adults Using Speech Acoustics: Validation with Plasma p-Tau217 and APOE-ε4 Status
Dadgostar M, Hanford LC, Tavakoli M, Arnold SE, Salat DH, Sitnikova T, Webb PK, Green JR et al.. medRxiv, 2026-01-16
Topic: Brain imaging, connectivity and assessment
INTRODUCTION We tested whether spontaneous speech acoustics provide a scalable digital marker of biologically defined Alzheimer’s disease (AD) risk. METHODS Forty-nine cognitively unimpaired older adults were stratified within APOE genotype into Low-, Moderate-, and High-Risk groups based on log₁₀-transformed plasma p-tau217. Acoustic features were extracted from spontaneous speech and entered into multiclass SVM classifiers with leave-one-out cross-validation, with and without genetic-algorithm feature selection and age. Parallel models using neuropsychological measures were evaluated for comparison. Feature contributions were interpreted using SHAP. RESULTS Speech-based models substantially outperformed cognition-only models and exceeded chance performance for three-group classification (33.3%), achieving up to 77% accuracy compared with 47% for neuropsychological models. SHAP analyses identified a compact, stage-dependent acoustic signature dominated by voice-quality, spectral-envelope, and formant-bandwidth features, with age contributing secondary effects. DISCUSSION Spontaneous speech acoustics capture p-tau217/APOE-defined AD risk despite preserved cognition, supporting speech as a scalable, biologically grounded biomarker for preclinical AD risk stratification.
Key findings
- RESULTS Speech-based models substantially outperformed cognition-only models and exceeded chance performance for three-group classification (33.3%), achieving up to 77% accuracy compared with 47% for neuropsychological models.
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Study details
- Effect size33.3%
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 24 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 15 of the 62 points we could judge it on, which is 24 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 15 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 15 of the 62 points we could judge it on is 24 out of 100. |
| Total | 24 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Dadgostar, M., Hanford, L. C., Tavakoli, M., Arnold, S. E., Salat, D. H., Sitnikova, T., et al. (2026). Detecting Preclinical Alzheimer’s Disease Risk in Cognitively Normal Adults Using Speech Acoustics: Validation with Plasma p-Tau217 and APOE-ε4 Status. medRxiv. https://doi.org/10.64898/2026.01.15.26344226
Vancouver
Dadgostar M, Hanford LC, Tavakoli M, Arnold SE, Salat DH, Sitnikova T, et al. Detecting Preclinical Alzheimer’s Disease Risk in Cognitively Normal Adults Using Speech Acoustics: Validation with Plasma p-Tau217 and APOE-ε4 Status. medRxiv. 2026. doi:10.64898/2026.01.15.26344226.
BibTeX
@article{dadgostar2026-7e9f0fc0,
author = {Dadgostar, M. and Hanford, L. C. and Tavakoli, M. and Arnold, S. E. and Salat, D. H. and Sitnikova, T. and Webb, P. K. and Green, JR. and others},
title = {{Detecting Preclinical Alzheimer’s Disease Risk in Cognitively Normal Adults Using Speech Acoustics: Validation with Plasma p-Tau217 and APOE-ε4 Status}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.01.15.26344226},
url = {https://doi.org/10.64898/2026.01.15.26344226}
}
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