Evidence map›Paper›PMID 41145341›Full record

ReviewThe journal of prevention of Alzheimer's disease2025

The role for artificial intelligence in identifying combination therapies for Alzheimer's disease.

Feixiong Cheng, Zhendong Sha, Yadi Zhou, Yuan Hou, Pengyue Zhang, Andrew A Pieper, Jeffrey Cummings

Abstract readReview
In one paragraph

Review 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 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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.

Feixiong ChengCleveland Clinic Genome Center, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Genomic Medicine, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA. Electronic address: chengf@ccf.org.
Zhendong ShaCleveland Clinic Genome Center, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Genomic Medicine, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH 44195, USA.
Yadi ZhouCleveland Clinic Genome Center, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Genomic Medicine, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH 44195, USA.
Yuan HouCleveland Clinic Genome Center, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Genomic Medicine, Cleveland Clinic Research, Cleveland Clinic, Cleveland, OH 44195, USA.
Pengyue ZhangDepartment of Biostatistics and Health Data Science, Indiana University, Indianapolis, IN 46202, USA.
Andrew A PieperDepartment of Psychiatry, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44106, USA; Brain Health Medicines Center, Harrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center, Cleveland, OH 44106, USA.
Jeffrey CummingsChambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, Kirk Kerkorian School of Medicine, University of Nevada Las Vegas, Las Vegas, NV 89154, USA.

Funding

Trial-Ready Cohort for Preclinical/Prodromal Alzheimer's DiseaseR01AG053798 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI AISEN, PAUL S., CUMMINGS, JEFFREY L. · 2017 to 2022
$39.4M
Renewal of Centers of Biomedical Research Excellence (COBRE) (Phase 2) CNTN - ResubmissionP20GM109025 · NIGMS · CLEVELAND CLINIC FOUNDATION · PI Robert J. Fox, Jefferson Kinney · 2015 to 2026
$22.8M
Chronic Traumatic Encephalopathy: Detection, Diagnosis, Course, and Risk FactorsU01NS093334 · NINDS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI CUMMINGS, JEFFREY L., REIMAN, ERIC MICHAEL · 2016 to 2022
$17.0M
Endophenotype Network-based Approaches to Prediction and Population-based Validation of In Silico Drug Repurposing for Alzheimer's DiseaseR01AG066707 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI Feixiong Cheng · 2020 to 2026
$4.9M
TREM2 Genotype-Informed Drug Repurposing and Combination Therapy Design for Alzheimer’s DiseaseR01AG076448 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI Feixiong Cheng, Li Gan · 2022 to 2026
$4.0M
Alzheimer's MultiOme Data Repurposing: Artificial Intelligence, Network Medicine, and Therapeutics DiscoveryU01AG073323 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI BEKRIS, LYNN, CHENG, FEIXIONG · 2021 to 2025
$4.0M
Alzheimer's Clinical Trial InnOvatioN (ACTION) InitiativeR35AG071476 · NIA · UNIVERSITY OF NEVADA LAS VEGAS · PI CUMMINGS, JEFFREY L. · 2021 to 2025
$2.9M
Alzheimer's Disease and Related Dementia-like Sequelae of SARS-CoV-2 Infection: Virus-Host Interactome, Neuropathobiology, and Drug RepurposingRF1AG082211 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI CHENG, FEIXIONG, PIEPER, ANDREW A · 2023 to 2023
$2.4M
Characterize neuronal and glial cell-specific vulnerability to proteinopathies in Alzheimer's disease using multimodal single-nuclei genomic and epigenomic approachesR01AG082118 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI BONAKDARPOUR, BORNA, CHENG, FEIXIONG · 2023 to 2025
$2.4M
Dark GPCR signaling underlying the Microbiome-Gut-Brain Axis for Alzheimer's Disease and Related DementiaRF1NS133812 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI BROWN, JONATHAN MARK, CHENG, FEIXIONG · 2023 to 2023
$2.3M
Microglial Activation and Inflammatory Endophenotypes Underlying Sex Differences of Alzheimer’s DiseaseR01AG084250 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI Feixiong Cheng, Justin D. Lathia · 2023 to 2026
$2.2M
A Multimodal, Multiscale and Multistage Systems Biology (M3SB) Infrastructure for Precision Medicine in Alzheimer’s Disease and LongevityR01AG092591 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI Feixiong Cheng, ANDREW J SAYKIN · 2025 to 2026
$1.6M
NIA NIH HHS R01 AG053798NIA NIH HHS R01 AG066707NIA NIH HHS R01 AG076448NIA NIH HHS R01 AG082118NIA NIH HHS R01 AG084250NIA NIH HHS R01 AG092462NIA NIH HHS R01 AG092591NIA NIH HHS R21 AG083003NIA NIH HHS R33 AG083003NIA NIH HHS R35 AG071476NIA NIH HHS RF1 AG082211NIA NIH HHS U01 AG073323NIGMS NIH HHS P20 GM109025NINDS NIH HHS RF1 NS133812NINDS NIH HHS U01 NS093334
6 · The paper itself

Abstract

Despite substantial investment in biomedical and pharmaceutical research over the past two decades, the global prevalence of Alzheimer's disease (AD) and AD-related dementias (AD/ADRD) is still rising. This underscores the significant unmet need for identifying effective disease-modifying therapies. Here, we provide a critical perspective on the application of data science and artificial intelligence (AI) to the rational design of drug combinations in AD and ADRD, addressing their potential to transform therapeutic development. We examine AI's current and prospective capabilities in therapeutic discovery, identify areas where AI-driven strategies can enhance drug combination development, and outline how multidisciplinary professionals in the field, including clinical trialists, neuropsychiatrists, pharmacologists, medicinal chemists, and computational scientists, can leverage these tools to address therapeutic gaps. We also highlight AI's role in synthesizing the rapidly growing amount of biomedical data in the field of AD/ADRD, especially clinical trials, biomarkers, multi-omics data (genomics, transcriptomics, proteomics, metabolomics, interactomics, and radiomics), and real-world patient data. We further explore AI's utility in prioritizing potential drug combination regimens and estimating clinical effect size in combination therapy trials for AD/ADRD. Lastly, we emphasize AI-powered network medicine methodologies for prioritizing drug combinations targeting AD/ADRD co-pathologies and summarize the challenges of their translation to clinical practice.

Indexed as

Alzheimer DiseaseArtificial IntelligenceDrug DiscoveryDrug Therapy, CombinationHumansAlzheimer's disease (AD)Artificial Intelligence (AI)Drug CombinationEndophenotype

Identifiers

PMID41145341
PMCPMC12627895

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.