Topic: Risk, prevention and care in population studies
The recently published results of the 18-month randomized controlled trial of lecanemab, reporting the efficacy of the drug in slowing the progression of early Alzheimer disease, quickly led to approval by the FDA and widespread acceptance of lecanemab treatment. However, there are a number of matters that deserve further consideration. The success of blinding was not assessed, even as infusion reactions and the cerebral pathology underlying amyloid-related imaging abnormalities could have signaled to many participants that they were on drug, potentially exerting a potent placebo effect. The value of the outcome to participants is not defined in the absolute terms necessary for clinical decision-making, and the difference attributable to lecanemab was between 18% and 46% of estimates of the minimal clinically important difference on the Clinical Dementia Rating Scale Sum of Boxes. The attenuation of change on the Alzheimer's Disease Assessment Scale-Cognitive 14 achieved by lecanemab at 18 months was 50% of that achieved by donepezil at 6 months. Lecanemab treatment imposes a high treatment burden. The fact that the burden commences at the initiation of lecanemab treatment, whereas the benefit accrues years later requires us to take into account value discounting over time, which would significantly reduce the benefit/burden ratio. Finally, treatment with monoclonal antibodies to cerebral amyloid has consistently been associated with progressive cerebral atrophy. At the least, these issues should be raised in treatment discussions with patients. They also suggest a need to very seriously reconsider how we evaluate clinical trial results preparatory to translating them into clinical practice. Some suggestions are provided.
Key findings
- The recently published results of the 18-month randomized controlled trial of lecanemab, reporting the efficacy of the drug in slowing the progression of early Alzheimer disease, quickly led to approval by the FDA and widespread acceptance of lecanemab treatment.
- The fact that the burden commences at the initiation of lecanemab treatment, whereas the benefit accrues years later requires us to take into account value discounting over time, which would significantly reduce the benefit/burden ratio.
- Finally, treatment with monoclonal antibodies to cerebral amyloid has consistently been associated with progressive cerebral atrophy.
- They also suggest a need to very seriously reconsider how we evaluate clinical trial results preparatory to translating them into clinical practice.
Why it matters
This commentary raises questions about the lecanemab trial, including that blinding success was not assessed and that the benefit was between 18% and 46% of estimates of the minimal clinically important difference on the Clinical Dementia Rating Scale Sum of Boxes. It also notes the treatment burden begins immediately while benefit accrues years later, which would reduce the benefit/burden ratio.
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Study details
- Study designrandomized controlled trial
- Evidence strengthHigh
How this study scored 57/100
Published in a leading specialty journal, and it is a randomised controlled trial. Scored zero for sample size, effect reported and studied in people because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (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 | 4 / 5 | 2024 — within 3 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 | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 2 / 7 | Cited 11 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.8 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 2 / 6 | Cited 2.6× 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 11 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Stephen E. Nadeau: h-index 38 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Florida: institution h-index 1,303 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38484213) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 100 | — |
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Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
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. Check the citation against the original before you use it.
APA 7th
Nadeau, S. E. (2024). Lecanemab Questions. Neurology. https://doi.org/10.1212/wnl.0000000000209320
Vancouver
Nadeau SE. Lecanemab Questions. Neurology. 2024. doi:10.1212/wnl.0000000000209320. PMID: 38484213.
BibTeX
@article{nadeau2024-38484213,
author = {Nadeau, S. E.},
title = {{Lecanemab Questions}},
journal = {Neurology},
year = {2024},
doi = {10.1212/wnl.0000000000209320},
pmid = {38484213},
url = {https://doi.org/10.1212/wnl.0000000000209320}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.