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Effect of reductions in amyloid levels on cognitive change in randomized trials: instrumental variable meta-analysis
Ackley SF, Zimmerman SC, Brenowitz WD, Tchetgen Tchetgen EJ, Gold AL, Manly JJ, Mayeda ER, Filshtein TJ et al.. BMJ (Clinical research ed.), 2021-02-25
Topic: Drug trials: efficacy and safety
Objective To evaluate trials of drugs that target amyloid to determine whether reductions in amyloid levels are likely to improve cognition. Design Instrumental variable meta-analysis. Setting 14 randomized controlled trials of drugs for the prevention or treatment of Alzheimer's disease that targeted an amyloid mechanism, identified from ClinicalTrials.gov. Population Adults enrolled in randomized controlled trials of amyloid targeting drugs. Inclusion criteria for trials vary, but typically include adults aged 50 years or older with a diagnosis of mild cognitive impairment or Alzheimer's disease, and amyloid positivity at baseline. Main outcome measures Analyses included trials for which information could be obtained on both change in brain amyloid levels measured with amyloid positron emission tomography and change in at least one cognitive test score reported for each randomization arm. Results Pooled results from the 14 randomized controlled trials were more precise than estimates from any single trial. The pooled estimate for the effect of reducing amyloid levels by 0.1 standardized uptake value ratio units was an improvement in the mini-mental state examination score of 0.03 (95% confidence interval -0.06 to 0.1) points. This study provides a web application that allows for the re-estimation of the results when new data become available and illustrates the magnitude of the new evidence that would be necessary to achieve a pooled estimate supporting the benefit of reducing amyloid levels. Conclusions Pooled evidence from available trials reporting both reduction in amyloid levels and change in cognition suggests that amyloid reduction strategies do not substantially improve cognition.
Key findings
- Results Pooled results from the 14 randomized controlled trials were more precise than estimates from any single trial.
- This study provides a web application that allows for the re-estimation of the results when new data become available and illustrates the magnitude of the new evidence that would be necessary to achieve a pooled estimate supporting the benefit of reducing amyloid levels.
- Conclusions Pooled evidence from available trials reporting both reduction in amyloid levels and change in cognition suggests that amyloid reduction strategies do not substantially improve cognition.
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Study details
- Study designmeta-analysis
- Evidence strengthHigh
How this study scored 74/100
Published in a leading specialty journal, and it is a meta-analysis pooling many studies. Scored zero for sample size, effect reported and studied in people 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 43 of the 58 points we could judge it on, which is 74 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (BMJ (Clinical research ed.)) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| 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 | 3 / 5 | 2021 — within 6 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 | A review of other studies — randomisation is not credited here |
| 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 33632704) |
| Free to read | 2 / 2 | Free to read |
| Points | 43 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 43 of the 58 points we could judge it on is 74 out of 100. |
| Total | 74 / 100 | — |
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APA 7th
Ackley, S. F., Zimmerman, S. C., Brenowitz, W. D., Tchetgen Tchetgen, E. J., Gold, A. L., Manly, J. J., et al. (2021). Effect of reductions in amyloid levels on cognitive change in randomized trials: instrumental variable meta-analysis. BMJ (Clinical research ed.). https://doi.org/10.1136/bmj.n156
Vancouver
Ackley SF, Zimmerman SC, Brenowitz WD, Tchetgen Tchetgen EJ, Gold AL, Manly JJ, et al. Effect of reductions in amyloid levels on cognitive change in randomized trials: instrumental variable meta-analysis. BMJ (Clinical research ed.). 2021. doi:10.1136/bmj.n156. PMID: 33632704.
BibTeX
@article{ackley2021-33632704,
author = {Ackley, S. F. and Zimmerman, S. C. and Brenowitz, W. D. and Tchetgen Tchetgen, E. J. and Gold, A. L. and Manly, J. J. and Mayeda, E. R. and Filshtein, T. J. and others},
title = {{Effect of reductions in amyloid levels on cognitive change in randomized trials: instrumental variable meta-analysis}},
journal = {BMJ (Clinical research ed.)},
year = {2021},
doi = {10.1136/bmj.n156},
pmid = {33632704},
url = {https://doi.org/10.1136/bmj.n156}
}