Evidence map›Paper›PMID 40316479›Full record

SynthesisThe journal of prevention of Alzheimer's disease2025

The efficacy and safety of anti-amyloid monoclonal antibody versus acetylcholinesterase inhibitor with an in-depth analysis across genotypes and disease stages: a systematic review and meta-analysis.

Chih-Wei Hsu, Tien-Wei Hsu, Yu-Chen Kao, Yu-Hsuan Lin, Trevor Thompson, Andre F Carvalho, Brendon Stubbs, Ping-Tao Tseng, Fu-Chi Yang, Chia-Kuang Tsai and 3 more

Abstract readComparative StudyMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The journal of prevention of Alzheimer's disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Treatments for Alzheimer's and the declaration of Helsinki.The journal of prevention of Alzheimer's disease · 2025
    Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Chih-Wei HsuDepartment of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Tien-Wei HsuDepartment of Psychiatry, E-DA Dachang Hospital, I-Shou University, Kaohsiung, Taiwan; Department of Psychiatry, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, I-Shou University, Kaohsiung , Taiwan.
Yu-Chen KaoDepartment of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, Taipei, Taiwan.
Yu-Hsuan LinInstitute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan; Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan.
Trevor ThompsonCentre for Chronic Illness and Ageing, University of Greenwich, London, UK.
Andre F CarvalhoIMPACT (Innovation in Mental and Physical Health and Clinical Treatment) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia.
Brendon StubbsInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Ping-Tao TsengInstitute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan; Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan; Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung City, Taiwan.
Fu-Chi YangDepartment of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Chia-Kuang TsaiDepartment of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Chia-Ling YuDepartment of Pharmacy, Chang Gung Memorial Hospital Linkou, Taoyuan, Taiwan.
Yu-Kang TuInstitute of Epidemiology & Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: yukangtu@ntu.edu.tw.
Chih-Sung LiangDepartment of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, Taipei, Taiwan. Electronic address: lcsyfw@gmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTo date, studies have not compared the efficacy and safety of monoclonal antibodies (mABs) with acetylcholinesterase inhibitors (AChEIs).

methodsFive electronic databases were systemic searched from inception to 10 November 2024 for double-blinded randomized controlled trial (RCT) of patients diagnosed with MCI or mild AD treated with mABs or AChEIs for at least 6 months. The primary outcome was change in cognitive function, measured by the Alzheimer's Disease Assessment Scale-cognitive subscale 14-item (ADAS-Cog) and Clinical Dementia Rating Scale-Sum of Boxes (CDR-SOB). The secondary outcomes were acceptability, tolerability, serious adverse events (SAE), and all -cause mortality. For mABs, amyloid-related imaging abnormalities-edema (ARIA-E), and amyloid-related imaging abnormalities-hemorrhage (ARIA-H) were also assessed. Subgroup analyses included (i) MCI versus mild AD; (ii) with versus without concomitant AD medications; and (iii) Apolipoprotein E (ApoE4) carriers versus non-carriers. Data were pooled using a random effects model within a Bayesian framework.

resultsThere were 8010 participants (mean age: 71.5 years) across seven mAB trials, and 4993 participants (mean age:70.7 years) in nine AChEI trials. When compared to placebo, only mABs, not AChEIs, were associated with a slower progression of cognitive decline on CDR-SOB (mean difference -0.41 (95 % credible interval -0.61 to -0.22); minimally important difference (MID) -1) and ADAS-Cog (-1.35 (-2.36 to -0.36), MID -2); however, these benefits of mABs did not reach MID across the two cognitive measurements. Besides, mABs were associated with a slower progression of cognitive decline on CDR-SOB (-0.30 (-0.60 to -0.001)) than AChEIs, although mABs and AChEIs did not differ across safety outcomes, including acceptability, tolerability, SAE, and all-cause mortality. Further analysis of mABs indicated that their efficacy did not differ by disease stage, concomitant AD medications, or APOE4 carrier status. However, APOE4 homozygotes carriers were associated with a 5.53-fold (2.48 to 13.07) increased odds of developing ARIA-E compared to non-carriers. Finally, lecanemab demonstrated relatively better efficacy and a more favorable profile on ARIA-E compared to aducanumab and donanemab.

conclusionsmABs were associated with a slower progression of cognitive decline than AChEIs; however, this effect did not reach the MID. The incidence of ARIA-E with mABs was associated with APOE4 carrier status and was not indicative of treatment efficacy.

Indexed as

Alzheimer DiseaseAntibodies, MonoclonalCholinesterase InhibitorsCognitive DysfunctionGenotypeHumansRandomized Controlled Trials as TopicTreatment OutcomeAntibodies, MonoclonalCholinesterase InhibitorsAlzheimer's diseaseApolipoprotein E4Cholinesterase inhibitorsCognitive functionMonoclonal antibodies

Identifiers

PMID40316479
PMCPMC12413725

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.