Evidence map›Paper›PMID 40675957›Full record

ArticleNature communications2025

AI-guided patient stratification improves outcomes and efficiency in the AMARANTH Alzheimer's Disease clinical trial.

Delshad Vaghari, Gayathri Mohankumar, Keith Tan, Andrew Lowe, Craig Shering, Peter Tino, Zoe Kourtzi

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–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

11 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Solving the 'Goldilocks problem' in dementia clinical trials with multimodal AI.The journal of prevention of Alzheimer's disease · 2025
    Article
  7. Article
  8. Collaborative AI for precision neurorehabilitation: a roadmap.Journal of neuroengineering and rehabilitation · 2025
    Review
  9. Review
  10. Review
  11. Brain-Targeting siRNA Delivery to Tackle Alzheimer's Disease.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology
    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

7 authors.

Delshad Vaghari *Department of Psychology, University of Cambridge, Cambridge, UK.
Gayathri Mohankumar *Centre for AI, Data Science & Artificial Intelligence, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, USA.
Keith TanNeuroscience, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Andrew LoweNeuroscience, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Craig SheringNeuroscience, BioPharmaceuticals R&D, AstraZeneca, Boston, USA.
Peter TinoSchool of Computer Science, University of Birmingham, Birmingham, United Kingdom.
Zoe KourtziDepartment of Psychology, University of Cambridge, Cambridge, UK. zk240@cam.ac.uk.ORCID http://orcid.org/0000-0001-9441-7832

Funding

Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI MONICA G. RIVERA-MINDT · 2016 to 2026
$226.7M
NIA NIH HHS U19 AG024904Royal Society INF\R2\202107Wellcome TrustWellcome Trust (Wellcome) 221633/Z/20/Z
6 · The paper itself

Abstract

Alzheimer's Disease (AD) drug discovery has been hampered by patient heterogeneity, and the lack of sensitive tools for precise stratification. Here, we demonstrate that our robust and interpretable AI-guided tool (predictive prognostic model, PPM) enhances precision in patient stratification, improving outcomes and decreasing sample size for a AD clinical trial. The AMARANTH trial of lanabecestat, a BACE1 inhibitor, was deemed futile, as treatment did not change cognitive outcomes, despite reducing β-amyloid. Employing the PPM, we re-stratify patients precisely using baseline data and demonstrate significant treatment effects; that is, 46% slowing of cognitive decline for slow progressive patients at earlier stages of neurodegeneration. In contrast, rapid progressive patients did not show significant change in cognitive outcomes. Our results provide evidence for AI-guided patient stratification that is more precise than standard patient selection approaches (e.g. β-amyloid positivity) and has strong potential to enhance efficiency and efficacy of future AD trials.

Indexed as

Alzheimer DiseaseAgedAged, 80 and overAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesCognitionCognitive DysfunctionFemaleHumansMalePatient SelectionPrognosisTreatment OutcomeAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesBACE1 protein, human

Identifiers

PMID40675957
PMCPMC12271323

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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.