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Sample size estimates for biomarker-based outcome measures in clinical trials in autosomal dominant Alzheimer's disease
Cash DM, Morgan KE, O'Connor A, Veale TD, Malone IB, Poole T, Benzinger TL, Gordon BA et al.. The journal of prevention of Alzheimer's disease, 2025-03-20
Topic: Amyloid, tau and blood-test diagnosis
Introduction Alzheimer disease (AD)-modifying therapies are approved for treatment of early-symptomatic AD. Autosomal dominant AD (ADAD) provides a unique opportunity to test therapies in presymptomatic individuals. Methods Using data from the Dominantly Inherited Alzheimer Network (DIAN), sample sizes for clinical trials were estimated for various cognitive, imaging, and CSF outcomes.
Key findings
- Autosomal dominant AD (ADAD) provides a unique opportunity to test therapies in presymptomatic individuals.
- Methods Using data from the Dominantly Inherited Alzheimer Network (DIAN), sample sizes for clinical trials were estimated for various cognitive, imaging, and CSF outcomes.
- Sample sizes were computed for detecting a reduction of either absolute levels of AD-related pathology (amyloid, tau) or change over time in neurodegeneration (atrophy, hypometabolism, cognitive change).
- Results Biomarkers measuring amyloid and tau pathology had required sample sizes below 200 participants per arm (examples CSF Aβ42/40: 47[95 %CI 25,104], cortical PIB 49[28,99], CSF p-tau181 74[48,125]) for a four-year trial in presymptomatic individuals (CDR=0) to have 80 % power (5 % statistical significance) to detect a 25 % reduction in absolute levels of pathology, allowing 40 % dropout.
Why it matters
This study used data from the Dominantly Inherited Alzheimer Network to estimate how many participants would be needed in clinical trials using cognitive, imaging, and cerebrospinal fluid outcomes in autosomal dominant Alzheimer's disease. It provides planning information for future trials and does not itself test any treatment.
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Study details
- Participants200
- Evidence strengthLow
How this study scored 44/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 42 of the 96 points we could judge it on, which is 44 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The journal of prevention of Alzheimer's disease) |
| Journal's citation record | 0 / 4 | The Journal of Prevention of Alzheimer s Disease: journal h-index 63 (OpenAlex, 2026-10-29) |
| 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 | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 200 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 | 1 / 7 | Cited 4 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 2.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 4 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 26 institution(s) in 7 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40118731) |
| Free to read | 2 / 2 | Free to read |
| Points | 42 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 42 of the 96 points we could judge it on is 44 out of 100. |
| Total | 44 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.tjpad.2025.100133
- PubMed: 40118731
- Original source →
- Free full text: The Journal of Prevention of Alzheimer s Disease →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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
Cash, D. M., Morgan, K. E., O'Connor, A., Veale, T. D., Malone, I. B., Poole, T., et al. (2025). Sample size estimates for biomarker-based outcome measures in clinical trials in autosomal dominant Alzheimer's disease. The journal of prevention of Alzheimer's disease. https://doi.org/10.1016/j.tjpad.2025.100133
Vancouver
Cash DM, Morgan KE, O'Connor A, Veale TD, Malone IB, Poole T, et al. Sample size estimates for biomarker-based outcome measures in clinical trials in autosomal dominant Alzheimer's disease. The journal of prevention of Alzheimer's disease. 2025. doi:10.1016/j.tjpad.2025.100133. PMID: 40118731.
BibTeX
@article{cash2025-40118731,
author = {Cash, D. M. and Morgan, K. E. and O'Connor, A. and Veale, T. D. and Malone, I. B. and Poole, T. and Benzinger, T. L. and Gordon, B. A. and others},
title = {{Sample size estimates for biomarker-based outcome measures in clinical trials in autosomal dominant Alzheimer's disease}},
journal = {The journal of prevention of Alzheimer's disease},
year = {2025},
doi = {10.1016/j.tjpad.2025.100133},
pmid = {40118731},
url = {https://doi.org/10.1016/j.tjpad.2025.100133}
}
Studies this one cites
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