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Anti-amyloid treatments in Alzheimer's disease: elegance, evidence and ethics
Daly T, Olluri A, Kurkinen M.. Advances in clinical and experimental medicine : official organ Wroclaw Medical University, 2024-12-01
Topic: Drug trials: efficacy and safety
The so-called "amyloid cascade hypothesis" provides an elegant explanation of Alzheimer's disease (AD), has motivated the amyloid-lowering therapeutic strategy, and led to the elaboration of a rich experimental and conceptual toolkit for the field to progress. But it might be incorrect. The scientific evidence base supporting the efficacy and safety of current anti-amyloid antibody treatments in AD is weak. Nevertheless, we argue that there is a bias towards the amyloid-lowering therapeutic strategy amongst key opinion leaders in the research and advocacy communities. To demonstrate this, we first focus on the AD lexicon: while any accrual of amyloid on a brain PET scan can now permit diagnosis/definition of AD, lowering positron emission tomography (PET) amyloid is considered disease modification, and treatment-induced side-effects are hidden behind neutral-sounding acronyms: ARIA (amyloid-β (Aβ)-related imaging abnormalities: brain bleeding and swelling) and ARPA (amyloid-β (Aβ) removal-related pseudo-atrophy: brain shrinkage). Second, we underline that drugmakers did not test anti-amyloid antibodies against the best proven interventions and did not adequately inform trial participants of risks, thus violating research ethics of the Declaration of Helsinki on 2 counts. In conclusion, we are critical of over-reliance on the idea that PET amyloid-lowering treatments for AD are a therapeutic revolution as claimed, and consider that optimism does not excuse a lack of scientific, regulatory, and ethical integrity. We argue for rigorous, properly controlled (e.g. donepezil) anti-amyloid trials demonstrating cognitive and functional benefit before accepting amyloid-lowering drugs as the new standard of care for AD patients.
Key findings
- In conclusion, we are critical of over-reliance on the idea that PET amyloid-lowering treatments for AD are a therapeutic revolution as claimed, and consider that optimism does not excuse a lack of scientific, regulatory, and ethical integrity.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, 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 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Advances in clinical and experimental medicine : official organ Wroclaw Medical University) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 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 | 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 | 2 / 2 | Indexed in PubMed (PMID 39698778) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
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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
Daly, T., Olluri, A., & Kurkinen, M. (2024). Anti-amyloid treatments in Alzheimer's disease: elegance, evidence and ethics. Advances in clinical and experimental medicine : official organ Wroclaw Medical University. https://doi.org/10.17219/acem/198674
Vancouver
Daly T, Olluri A, Kurkinen M. Anti-amyloid treatments in Alzheimer's disease: elegance, evidence and ethics. Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2024. doi:10.17219/acem/198674. PMID: 39698778.
BibTeX
@article{daly2024-39698778,
author = {Daly, T. and Olluri, A. and Kurkinen, M.},
title = {{Anti-amyloid treatments in Alzheimer's disease: elegance, evidence and ethics}},
journal = {Advances in clinical and experimental medicine : official organ Wroclaw Medical University},
year = {2024},
doi = {10.17219/acem/198674},
pmid = {39698778},
url = {https://doi.org/10.17219/acem/198674}
}
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