Evidence map›Paper›PMID 39800453›Full record

ArticleThe journal of prevention of Alzheimer's disease2025

Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation.

Jeffrey Cummings, Michael Gold, Mark Mintun, Michael Irizarry, Andrew von Eschenbach, Suzanne Hendrix, Donald Berry, Cristina Sampaio, Kaycee Sink, Jaren Landen and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article 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 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

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

  1. Pooled it
  2. Beyond the Cochrane review: Re-evaluating anti-amyloid therapy in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  3. Article
  4. The roles of biomarkers in Alzheimer's disease clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. Alzheimer Combination Therapies: Overview and Scenarios.The journal of prevention of Alzheimer's disease · 2025
    Review
  10. Review
  11. Article
  12. CTAD taskforce: genetic therapies in Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025
    Review
  13. Review
  14. Doxycycline: An essential tool for Alzheimer's disease.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025
    Review
  15. Review
  16. Article
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

18 authors.

Jeffrey CummingsChambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas, NV, USA.
Michael GoldCompass Pathways, London, UK.
Mark MintunEli Lilly and Company, Indianapolis, IN, USA.
Michael IrizarryEisai Inc, Nutley, NJ, USA.
Andrew von EschenbachSamaritan Health Initiatives, Houston, TX, USA.
Suzanne HendrixPentara Corporation, Millcreek, UT, USA.
Donald BerryDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, Berry Consultants, LLC, Austin TX, USA.
Cristina SampaioCHDI Management, Inc. the company that manages the scientific activities of CHDI Foundation Princeton, NJ, USA, Faculdade Medicina University of Lisbon, Lisboa, Portugal.
Kaycee SinkGenentech Inc., South San Francisco, CA, USA.
Jaren LandenBiogen, Cambridge, MA, USA at the time of advisory board.
Miia KivipeltoDepartment of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden, Ageing Epidemiology Research Unit (AGE), School of Public Health, Faculty of Medicine, Imperial College London, UK, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
Michael GrundmanGlobal R&D Partners, LLC., San Diego, CA, USA and University of California, San Diego, San Diego, CA, USA.
Steven E ArnoldDepartment of Neurology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
Allan GreenSDG, LLC, Cambridge, MA, USA.
Katherine PartrickIndependent Researcher, Albuquerque, NM, USA.
Laura NisenbaumAlzheimer's Drug Discovery Foundation, New York, NY, USA.
Aaron BursteinAlzheimer's Drug Discovery Foundation, New York, NY, USA.
Howard FillitAlzheimer's Drug Discovery Foundation, New York, NY, USA. Electronic address: hfillit@alzdiscovery.org.

Funding

Renewal of Centers of Biomedical Research Excellence (COBRE) (Phase 2) CNTN - ResubmissionP20GM109025 · NIGMS · CLEVELAND CLINIC FOUNDATION · PI JESSICA KIRKLAND CALDWELL · 2015 to 2026
$22.8M
Alzheimer's Clinical Trial InnOvatioN (ACTION) InitiativeR35AG071476 · NIA · UNIVERSITY OF NEVADA LAS VEGAS · PI CUMMINGS, JEFFREY L. · 2021 to 2025
$2.9M
NIA NIH HHS R35 AG071476NIGMS NIH HHS P20 GM109025
6 · The paper itself

Abstract

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas. Experts agreed on the need to prioritize a combination therapy approach that encompasses a wide range of targets associated with aging and the underlying biology of Alzheimer's disease. Progress in combination therapy could be accelerated by leveraging preclinical research and Phase 1 and 2A trials to identify the most promising combinations for further development, exploring repurposed agents with available preclinical and clinical data, building collaborations across sectors to support operational challenges, and planning for the likely impact of anti-amyloid beta-protein monoclonal antibody therapies on future clinical trial designs.

Indexed as

Alzheimer DiseaseClinical Trials as TopicDrug DiscoveryAdvisory CommitteesDrug Therapy, CombinationHumansAlzheimer's diseaseBiomarkersClinical trialsCombination therapyPreclinical research

Identifiers

PMID39800453
PMCPMC12183988

What OpenQuestion holds

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LicenceCC BY
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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 OpenQuestion graph.