Evidence mapPaperPMID 41068898Full record

SynthesisBMC medical genomics2025

The role of genetic polymorphisms on drug response in Alzheimer's disease: a systematic review.

Fresthel Monica M Climacosa, Eric David B Ornos, Nicole Clarence Louise L Gapaz, Mary Gale R Guantia, Joana Marie C Cruz, Rafael Vincent M Manalo, Melody L Yu, Almeera P Qureshi, Ajina C Carampel, Joannes Luke B Asis and 3 more

Abstract readSystematic Review
In one paragraph

Synthesis in BMC medical genomics, 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

13 authors.

Fresthel Monica M ClimacosaMulti-Omics Research Program for Health, College of Medicine, University of the Philippines Manila, Manila, Philippines. fmclimacosa@up.edu.ph.
Eric David B OrnosMulti-Omics Research Program for Health, College of Medicine, University of the Philippines Manila, Manila, Philippines.
Nicole Clarence Louise L GapazMulti-Omics Research Program for Health, College of Medicine, University of the Philippines Manila, Manila, Philippines.
Mary Gale R GuantiaMulti-Omics Research Program for Health, College of Medicine, University of the Philippines Manila, Manila, Philippines.
Joana Marie C CruzMulti-Omics Research Program for Health, College of Medicine, University of the Philippines Manila, Manila, Philippines.
Rafael Vincent M ManaloMulti-Omics Research Program for Health, College of Medicine, University of the Philippines Manila, Manila, Philippines.
Melody L YuMulti-Omics Research Program for Health, College of Medicine, University of the Philippines Manila, Manila, Philippines.
Almeera P QureshiMulti-Omics Research Program for Health, College of Medicine, University of the Philippines Manila, Manila, Philippines.
Ajina C CarampelMulti-Omics Research Program for Health, College of Medicine, University of the Philippines Manila, Manila, Philippines.
Joannes Luke B AsisMulti-Omics Research Program for Health, College of Medicine, University of the Philippines Manila, Manila, Philippines.
John Carlo B ReyesMulti-Omics Research Program for Health, College of Medicine, University of the Philippines Manila, Manila, Philippines.
Aira B DacasinMulti-Omics Research Program for Health, College of Medicine, University of the Philippines Manila, Manila, Philippines.
Veeda Michelle M AnlacanMulti-Omics Research Program for Health, College of Medicine, University of the Philippines Manila, Manila, Philippines.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disorder, affecting over 32 million people globally. The variability in treatment response to AD medications is influenced by genetic factors, sex, comorbidities, and medication history. Pharmacogenomics, the study of how an individual’s genetic makeup influences drug response, offers a promising approach to understanding these differences. This systematic review investigated the role of genetic polymorphisms in affecting treatment outcomes in AD. Following PRISMA guidelines, we systematically searched PubMed, Scopus, Cochrane, and PharmGKB databases for studies on AD, pharmacogenomics, and treatment response. Ten researchers independently screened the articles, with two independent reviewers resolving conflicts. A total of 1126 records were identified, and after removing duplicates and screening, 58 studies met inclusion criteria. APOE emerged as the most consistently studied gene, with ε2 and ε3 alleles generally associated with better responses to acetylcholinesterase inhibitors (AChEIs) and NMDA receptor antagonists, while ε4 carriage predicted poorer outcomes. The CYP2D610 allele, common in East Asian populations, was linked to enhanced donepezil response due to slower drug metabolism. Other genes, including ABCA1, A2M, CHRNA7, CHRFAM7A, and CHAT, showed potential associations with treatment response, particularly with AChEIs, though results varied across populations and study designs. Polymorphisms in inflammatory, metabolic, and vascular genes such as IL6, IDE, and ACE were also associated with cognitive outcomes, but findings were largely exploratory. In conclusion, APOE and CYP2D6 remain the most promising pharmacogenetic markers in AD, particularly for guiding donepezil therapy. However, evidence remains inconsistent due to varying study designs, populations, and clinical metrics. Additional genes show potential but require further validation. Larger, multiethnic studies with standardized treatment protocols and outcomes are needed to establish the clinical utility of pharmacogenomics in AD therapy.

Indexed as

Alzheimer DiseasePolymorphism, GeneticApolipoproteins ECholinesterase InhibitorsHumansPharmacogeneticsApolipoproteins ECholinesterase InhibitorsAlzheimer’s diseaseDrug responseGenetic polymorphismsPharmacogenomics

Identifiers

PMID41068898
PMCPMC12512622

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.