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Randomized Trial of Verubecestat for Prodromal Alzheimer's Disease
Egan MF, Kost J, Voss T, Mukai Y, Aisen PS, Cummings JL, Tariot PN, Vellas B et al.. The New England journal of medicine, 2019-04-01
Topic: Amyloid, tau and blood-test diagnosis
Background Prodromal Alzheimer's disease offers an opportunity to test the effect of drugs that modify the deposition of amyloid in the brain before the onset of dementia. Verubecestat is an orally administered β-site amyloid precursor protein-cleaving enzyme 1 (BACE-1) inhibitor that blocks production of amyloid-beta (Aβ). The drug did not prevent clinical progression in a trial involving patients with mild-to-moderate dementia due to Alzheimer's disease.
Key findings
- Verubecestat is an orally administered β-site amyloid precursor protein-cleaving enzyme 1 (BACE-1) inhibitor that blocks production of amyloid-beta (Aβ).
- The drug did not prevent clinical progression in a trial involving patients with mild-to-moderate dementia due to Alzheimer's disease.
- Methods We conducted a randomized, double-blind, placebo-controlled, 104-week trial to evaluate verubecestat at doses of 12 mg and 40 mg per day, as compared with placebo, in patients who had memory impairment and elevated brain amyloid levels but whose condition did not meet the case definition of dementia.
- The primary outcome was the change from baseline to week 104 in the score on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB; scores range from 0 to 18, with higher scores indicating worse cognition and daily function).
Why it matters
This trial tested verubecestat, a BACE-1 inhibitor that blocks production of amyloid-beta, in patients with prodromal Alzheimer's disease. The drug did not prevent clinical progression in an earlier trial involving patients with mild-to-moderate dementia due to Alzheimer's disease.
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Study details
- Participants1,454
- Effect size97.51%
- Evidence strengthHigh
How this study scored 83/100
Published in a top-tier journal, and it is a large phase 3 trial.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (The New England journal of medicine) |
| Journal's citation record | 4 / 4 | New England Journal of Medicine: journal h-index 1,505 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A large phase 3 trial (from PubMed type “Clinical Trial, Phase III”) |
| 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 | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,454 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 | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 6 / 7 | Cited 544 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 60.4 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 6 / 6 | Cited 50.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 26 other studies in this library |
| Still being cited | 3 / 4 | Cited 141 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author David Michelson: h-index 39 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Inserm: institution h-index 1,988 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30970186) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 83 / 100 | — |
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Read the original
- DOI: 10.1056/nejmoa1812840
- PubMed: 30970186
- Original source →
- Free full text: New England Journal of Medicine →
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
Egan, M. F., Kost, J., Voss, T., Mukai, Y., Aisen, P. S., Cummings, J. L., et al. (2019). Randomized Trial of Verubecestat for Prodromal Alzheimer's Disease. The New England journal of medicine. https://doi.org/10.1056/nejmoa1812840
Vancouver
Egan MF, Kost J, Voss T, Mukai Y, Aisen PS, Cummings JL, et al. Randomized Trial of Verubecestat for Prodromal Alzheimer's Disease. The New England journal of medicine. 2019. doi:10.1056/nejmoa1812840. PMID: 30970186.
BibTeX
@article{egan2019-30970186,
author = {Egan, M. F. and Kost, J. and Voss, T. and Mukai, Y. and Aisen, P. S. and Cummings, J. L. and Tariot, P. N. and Vellas, B. and others},
title = {{Randomized Trial of Verubecestat for Prodromal Alzheimer's Disease}},
journal = {The New England journal of medicine},
year = {2019},
doi = {10.1056/nejmoa1812840},
pmid = {30970186},
url = {https://doi.org/10.1056/nejmoa1812840}
}
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