Home › Research › Treatments
Targeting Prodromal Alzheimer Disease With Avagacestat: A Randomized Clinical Trial
Coric V, Salloway S, van Dyck CH, Dubois B, Andreasen N, Brody M, Curtis C, Soininen H et al.. JAMA neurology, 2015-11-01
Topic: Amyloid, tau and blood-test diagnosis
Results Of the 263 participants in the treatment phase, 132 were randomized to avagacestat and 131 to placebo; an additional 102 participants were observed in an untreated observational cohort. No significant treatment differences were observed in the avagacestat vs placebo arm in key clinical outcome measures. Conclusions and relevance Avagacestat did not demonstrate efficacy and was associated with adverse dose-limiting effects. This PDAD population receiving avagacestat or placebo had higher rates of clinical progression to dementia and greater brain atrophy compared with CSF biomarker-negative participants. The CSF biomarkers and amyloid positron emission tomography imaging were correlated, suggesting that either modality could be used to confirm the presence of cerebral amyloidopathy and identify PDAD.
Key findings
- Results Of the 263 participants in the treatment phase, 132 were randomized to avagacestat and 131 to placebo; an additional 102 participants were observed in an untreated observational cohort.
- No significant treatment differences were observed in the avagacestat vs placebo arm in key clinical outcome measures.
- Conclusions and relevance Avagacestat did not demonstrate efficacy and was associated with adverse dose-limiting effects.
- This PDAD population receiving avagacestat or placebo had higher rates of clinical progression to dementia and greater brain atrophy compared with CSF biomarker-negative participants.
- The CSF biomarkers and amyloid positron emission tomography imaging were correlated, suggesting that either modality could be used to confirm the presence of cerebral amyloidopathy and identify PDAD.
Why it matters
In this randomized trial of 263 people with prodromal Alzheimer's disease, avagacestat did no better than placebo on key clinical measures and caused dose-limiting side effects. Participants identified by spinal-fluid biomarkers, whether given the drug or placebo, progressed to dementia more often and lost more brain volume than biomarker-negative participants. The authors also found that spinal-fluid tests and amyloid PET scans agreed closely enough that they suggest either one could be used to identify these patients.
New to this subject? Start with our plain-English guide: Treatments →
Study details
- Study designrandomized controlled trial
- Participants263
- Effect size19.6%; 37.1%; 23.7%
- Evidence strengthHigh
How this study scored 74/100
Published in a leading specialty journal, and it is a randomised controlled trial.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 263 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 5 / 7 | Cited 239 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 18.4 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 4 / 6 | Cited 10.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 3 / 4 | Cited 58 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Robert Berman: h-index 51 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Yale University: institution h-index 1,927 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 16 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26414022) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 74 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamaneurol.2015.0607
- PubMed: 26414022
- Original source →
- Free full text: jamanetwork.com →
Full text: free to read — Unpaywall lists this copy as free to read: the link above (checked 10 Oct 2026).
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
Coric, V., Salloway, S., van Dyck, C. H., Dubois, B., Andreasen, N., Brody, M., et al. (2015). Targeting Prodromal Alzheimer Disease With Avagacestat: A Randomized Clinical Trial. JAMA neurology. https://doi.org/10.1001/jamaneurol.2015.0607
Vancouver
Coric V, Salloway S, van Dyck CH, Dubois B, Andreasen N, Brody M, et al. Targeting Prodromal Alzheimer Disease With Avagacestat: A Randomized Clinical Trial. JAMA neurology. 2015. doi:10.1001/jamaneurol.2015.0607. PMID: 26414022.
BibTeX
@article{coric2015-26414022,
author = {Coric, V. and Salloway, S. and van Dyck, C. H. and Dubois, B. and Andreasen, N. and Brody, M. and Curtis, C. and Soininen, H. and others},
title = {{Targeting Prodromal Alzheimer Disease With Avagacestat: A Randomized Clinical Trial}},
journal = {JAMA neurology},
year = {2015},
doi = {10.1001/jamaneurol.2015.0607},
pmid = {26414022},
url = {https://doi.org/10.1001/jamaneurol.2015.0607}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 19.
Later studies that cite this one
11 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Treatments
Also tagged “double-blind”
783 studies in the library carry the topic tag “double-blind”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 783 tagged studies.