SynthesisBMJ (Clinical research ed.)2021
Effect of reductions in amyloid levels on cognitive change in randomized trials: instrumental variable meta-analysis.
Synthesis in BMJ (Clinical research ed.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 97 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
97 citing papers in PubMed, 5 syntheses or guidelines pooled it, 173 citations in OpenAlex.
- Amyloid-beta-targeting monoclonal antibodies for people with mild cognitive impairment or mild dementia due to Alzheimer's disease.The Cochrane database of systematic reviews · 2026Pooled it
- Evaluating amyloid-beta as a surrogate endpoint in trials of anti-amyloid-beta drugs in Alzheimer's disease: a Bayesian meta-analysis.Journal of comparative effectiveness research · 2026Pooled it
- Assessing clinical progression measures in Alzheimer's disease trials: A systematic review and meta-analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Pooled it
- Accelerated Brain Volume Loss Caused by Anti-β-Amyloid Drugs: A Systematic Review and Meta-analysis.Neurology · 2023Pooled it
- Safety and Efficacy of Monoclonal Antibodies for Alzheimer's Disease: A Systematic Review and Meta-Analysis of Published and Unpublished Clinical Trials.Journal of Alzheimer's disease : JAD · 2022Pooled it
- Implications of the Approval of Lecanemab for Alzheimer Disease Patient Care: Incremental Step or Paradigm Shift?Neurology · 2023Trial
- Letter to the editor: Amyloid-beta-targeting monoclonal antibodies for people with mild cognitive impairment or mild dementia due to Alzheimer's disease.The Cochrane database of systematic reviews · 2026Article
- Amyloid-beta-targeting monoclonal antibodies in early Alzheimer's disease: a cochrane review summary and appraisal for the neurological community.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Methodological Considerations for Quantile Aggregation in Alzheimer Disease Trials.JAMA neurology · 2026Article
- Passive amyloid-β immunotherapy in Alzheimer's disease: a multicellular clearance system beyond plaque removal.Molecular neurodegeneration · 2026Review
- Low Sensitivity of Neuropsychological Scales Hinder Detection of Potential Benefit of Treatments in Alzheimer's Disease: A Position Paper.European journal of neurology · 2026Review
- A review of evidence supporting amyloid beta reduction as a surrogate endpoint in Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2026Review
- Pharmacologic reversal of advanced Alzheimer's disease in mice and identification of potential therapeutic nodes in human brain.Cell reports. Medicine · 2026Article
- Golgi Fragmentation as a Potential Link Between SARS-CoV-2 Infection and Alzheimer's Disease: Mechanisms and Implications for Neurodegeneration in Long COVID.Sub-cellular biochemistry · 2026Review
- Alzheimer Syndrome or Age-Related Dementia-History, Therapy and Prevention.Journal of clinical medicine · 2025Article
- Aberrant Mitochondrial Metabolism in Alzheimer's Disease Links Energy Stress with Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Alzheimer's Disease Etiology Hypotheses and Therapeutic Strategies: A Perspective.International journal of molecular sciences · 2025Review
- Mechanisms of interventions targeting modifiable factors for dementia risk reduction.Molecular neurodegeneration · 2025Review
- Cytoskeletal Proteins and Alzheimer's Disease Pathogenesis: Focusing on the Interplay with Tau Pathology.Biomolecules · 2025Review
- Harnessing human iPSC-microglia for CNS-wide delivery of disease-modifying proteins.Cell stem cell · 2025Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Erratum issued
Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
objectiveTo evaluate trials of drugs that target amyloid to determine whether reductions in amyloid levels are likely to improve cognition.
designInstrumental variable meta-analysis.
setting14 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 measuresAnalyses 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.
resultsPooled 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.
conclusionsPooled evidence from available trials reporting both reduction in amyloid levels and change in cognition suggests that amyloid reduction strategies do not substantially improve cognition.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.