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78/100

✓ Peer-reviewed alzhub usefulness score 78 out of 100. Treatments

Topic: Amyloid, tau and blood-test diagnosis

Background and objectives To evaluate brain volume changes caused by different subclasses of anti-β-amyloid (Aβ) drugs trailed in patients with Alzheimer disease. Methods PubMed, Embase, and ClinicalTrials.gov databases were searched for clinical trials of anti-Aβ drugs. This systematic review and meta-analysis included adults enrolled in randomized controlled trials of anti-Aβ drugs (n = 8,062-10,279). The inclusion criteria were as follows: (1) randomized controlled trials of patients treated with anti-Aβ drugs that have demonstrated to favorably change at least one biomarker of pathologic Aβ and (2) detailed MRI data sufficient to assess the volumetric changes in at least one brain region. MRI brain volumes were used as the primary outcome measure; brain regions commonly reported include hippocampus, lateral ventricle, and whole brain. Amyloid-related imaging abnormalities (ARIAs) were investigated when reported in clinical trials. Of the 145 trials reviewed, 31 were included in the final analyses. Results A meta-analysis on the highest dose of each trial on hippocampus, ventricle, and whole brain revealed drug-induced acceleration of volume changes that varied by anti-Aβ drug class. Secretase inhibitors accelerated atrophy to the hippocampus (Δ placebo - Δ drug: -37.1 µL [19.6% more than placebo]; 95% CI -47.0 to -27.1) and whole brain (Δ placebo - Δ drug: -3.3 mL [21.8% more than placebo]; 95% CI -4.1 to 2.5). Conversely, ARIA-inducing monoclonal antibodies accelerated ventricular enlargement (Δ placebo - Δ drug: +2.1 mL [38.7% more than placebo]; 95% CI 1.5-2.8) where a striking correlation between ventricular volume and ARIA frequency was observed ( r = 0.86, p = 6.22 × 10 -7 ). Mild cognitively impaired participants treated with anti-Aβ drugs were projected to have a material regression toward brain volumes typical of Alzheimer dementia ∼8 months earlier than if they were untreated. Discussion These findings reveal the potential for anti-Aβ therapies to compromise long-term brain health by accelerating brain atrophy and provide new insight into the adverse impact of ARIA. Six recommendations emerge from these findings.

Key findings

The inclusion criteria were as follows: (1) randomized controlled trials of patients treated with anti-Aβ drugs that have demonstrated to favorably change at least one biomarker of pathologic Aβ and (2) detailed MRI data sufficient to assess the volumetric changes in at least one brain region.
Results A meta-analysis on the highest dose of each trial on hippocampus, ventricle, and whole brain revealed drug-induced acceleration of volume changes that varied by anti-Aβ drug class.
Discussion These findings reveal the potential for anti-Aβ therapies to compromise long-term brain health by accelerating brain atrophy and provide new insight into the adverse impact of ARIA.
Six recommendations emerge from these findings.

Why it matters

This meta-analysis found that anti-β-amyloid drugs accelerated brain volume loss, with the amount varying by drug class. Secretase inhibitors accelerated atrophy to the hippocampus and whole brain compared to placebo.

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Study details

Study designsystematic review
Participants8,062
Effect size19.6%; 21.8%; 38.7%
Evidence strengthHigh

How this study scored 78/100

Published in a leading specialty journal, and it is a systematic review of all the studies on the question.

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	12 / 12	A systematic review of all the studies on the question
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	2023 — within 6 year(s) of the newest study here
Sample size	3 / 4	8,062 participants
Effect reported	2 / 3	Effect reported as a number, without an interval or test
Studied in people	3 / 3	Studied in people (participant count stated)
Randomised / blinded	0 / 2	A review of other studies — randomisation is not credited here
Times cited	5 / 7	Cited 213 times (OpenAlex, 2026-10-10)
Citations per year	4 / 5	42.6 citations a year over 5 year(s) since 2023
Impact for its field and year	5 / 6	Cited 31.2× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	3 / 6	Cited by 11 other studies in this library
Still being cited	3 / 4	Cited 170 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	3 / 4	Last-listed author Scott Ayton: h-index 63 (OpenAlex, whole career)
Institution's track record	1 / 3	The University of Melbourne: institution h-index 1,342 (OpenAlex)
Multi-centre collaboration	1 / 3	OpenAlex lists 2 institution(s) in 1 country
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 36973044)
Free to read	0 / 2	Behind a paywall — scores zero
Total	78 / 100	—

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Cite this study APA, Vancouver, BibTeX · download .bib or .ris

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APA 7th

Alves, F., Kalinowski, P., & Ayton, S. (2023). Accelerated Brain Volume Loss Caused by Anti-β-Amyloid Drugs: A Systematic Review and Meta-analysis. Neurology. https://doi.org/10.1212/wnl.0000000000207156

Vancouver

Alves F, Kalinowski P, Ayton S. Accelerated Brain Volume Loss Caused by Anti-β-Amyloid Drugs: A Systematic Review and Meta-analysis. Neurology. 2023. doi:10.1212/wnl.0000000000207156. PMID: 36973044.

BibTeX

@article{alves2023-36973044,
  author  = {Alves, F. and Kalinowski, P. and Ayton, S.},
  title   = {{Accelerated Brain Volume Loss Caused by Anti-β-Amyloid Drugs: A Systematic Review and Meta-analysis}},
  journal = {Neurology},
  year    = {2023},
  doi     = {10.1212/wnl.0000000000207156},
  pmid    = {36973044},
  url     = {https://doi.org/10.1212/wnl.0000000000207156}
}

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