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Test-retest reliability of plasma biomarkers and digital cognitive metrics at clinically meaningful timescales
Toniolo S, Zhao S, Broulidakis M, Fower A, Gendarini C, Scholcz A, Griffiths T, Zetterberg H et al.. Research Square, 2026-07-23
Topic: Plasma and spinal-fluid biomarkers
Background Digital cognitive testing and plasma biomarkers have emerged as key players for population screening and measuring drug efficacy in clinical trials for Alzheimer’s Disease (AD). Understanding test-retest reliability of these tools is essential to estimate meaningful effects of an intervention over time. Whilst some data exist on variability of plasma and digital biomarkers at very short time frames or annually, studies conducted at intermediate time scales are lacking. Data on impact on this variability on clinical decision-making are also rare. Methods Paired testing of plasma biomarkers and digital cognition was performed at 0, 3 and 6 months in a cohort of 92 individuals (55 cognitively unimpaired healthy controls (HC) and 37 patients with early AD dementia (AD)). Plasma biomarkers examined included pTau217, pTau181, NfL, GFAP and the Aβ42/40 ratio. OCTAL (Oxford Cognitive Testing Portal) digital cognitive testing platform was used to measure cognition. Results pTau181 emerged as the plasma biomarker with worst test-retest reliability and was the only measure where repeating the sample improved accuracy in group discrimination. None of the digital measures showed further improvement in diagnostic accuracy if repeated over time, reflecting high reliability. Individual metrics showed different reliability profiles based on the index used to measure variability (Coefficient of variation or Intraclass Correlation Coefficient) and varied within groups (HC and AD). Conclusion Test-retest reliability measures are essential for interpretation of meaningful effects over time for plasma and digital outcomes.
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APA 7th
Toniolo, S., Zhao, S., Broulidakis, M., Fower, A., Gendarini, C., Scholcz, A., et al. (2026). Test-retest reliability of plasma biomarkers and digital cognitive metrics at clinically meaningful timescales. Research Square. https://doi.org/10.21203/rs.3.rs-10016306/v1
Vancouver
Toniolo S, Zhao S, Broulidakis M, Fower A, Gendarini C, Scholcz A, et al. Test-retest reliability of plasma biomarkers and digital cognitive metrics at clinically meaningful timescales. Research Square. 2026. doi:10.21203/rs.3.rs-10016306/v1.
BibTeX
@article{toniolo2026-3b9d2254,
author = {Toniolo, S. and Zhao, S. and Broulidakis, M. and Fower, A. and Gendarini, C. and Scholcz, A. and Griffiths, T. and Zetterberg, H. and others},
title = {{Test-retest reliability of plasma biomarkers and digital cognitive metrics at clinically meaningful timescales}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10016306/v1},
url = {https://doi.org/10.21203/rs.3.rs-10016306/v1}
}
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Key findings
- Results pTau181 emerged as the plasma biomarker with worst test-retest reliability and was the only measure where repeating the sample improved accuracy in group discrimination.
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Study details
- Participants92
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 34 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, effect reported 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 21 of the 62 points we could judge it on, which is 34 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| 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 | 3 / 5 | Rated “moderate” 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 | 1 / 4 | 92 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| 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 | 2 / 2 | Free to read |
| Points | 21 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 21 of the 62 points we could judge it on is 34 out of 100. |
| Total | 34 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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