ArticleEuropean journal of clinical pharmacology2011
BCHE and CYP2D6 genetic variation in Alzheimer's disease patients treated with cholinesterase inhibitors.
Article in European journal of clinical pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 3 of them syntheses that pooled it.
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Who cites it
15 citing papers in PubMed, 3 syntheses or guidelines pooled it, 49 citations in OpenAlex.
- The role of genetic polymorphisms on drug response in Alzheimer's disease: a systematic review.BMC medical genomics · 2025Pooled it
- Predictors of response to acetylcholinesterase inhibitors in dementia: A systematic review.Frontiers in neuroscience · 2022Pooled it
- Pooled it
- Donepezil plasma concentrations, CYP2D6 and CYP3A4 phenotypes, and cognitive outcome in Alzheimer's disease.European journal of clinical pharmacology · 2016Trial
- Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A, ABCB1, POR and NR1I2 genotypes on donepezil clearance.British journal of clinical pharmacology · 2014Trial
- Single nucleotide polymorphisms affecting galantamine binding to acetylcholinesterase in Alzheimer's disease: a structural bioinformatics study.Journal of computer-aided molecular design · 2026Article
- A Comprehensive Review on Potential Molecular Drug Targets for the Management of Alzheimer's Disease.Central nervous system agents in medicinal chemistry · 2024Review
- Metals and Metal-Nanoparticles in Human Pathologies: From Exposure to Therapy.Molecules (Basel, Switzerland) · 2021Review
- Gene Polymorphisms Affecting the Pharmacokinetics and Pharmacodynamics of Donepezil Efficacy.Frontiers in pharmacology · 2020Review
- CYP2D6 Predicts Plasma Donepezil Concentrations in a Cohort of Thai Patients with Mild to Moderate Dementia.Pharmacogenomics and personalized medicine · 2020Article
- Recent Developments in Metal-Based Drugs and Chelating Agents for Neurodegenerative Diseases Treatments.International journal of molecular sciences · 2019Review
- Pharmacodynamic, pharmacokinetic and pharmacogenetic aspects of drugs used in the treatment of Alzheimer's disease.Clinical pharmacokinetics · 2013Review
- CHRNA7 polymorphisms and response to cholinesterase inhibitors in Alzheimer's disease.PloS one · 2013Article
- Influence of rs1080985 single nucleotide polymorphism of the CYP2D6 gene on response to treatment with donepezil in patients with alzheimer's disease.Neuropsychiatric disease and treatment · 2013Article
- Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeCholinesterase inhibitors are commonly prescribed to patients with Alzheimer's disease (AD) to enhance cholinergic neurotransmission. Differential response to these treatments has been observed, and claims have been made that individual genetic variants may influence the pharmacokinetic and pharmacodynamic properties of these drugs. Here we assess the effects of genetic variation at two loci involved in the activity of cholinesterase inhibitors on longitudinal clinical change in AD patients being treated with donepezil, galantamine, and rivastigmine.
methodsThis was an open study in which 171 Italian AD patients treated with donepezil (n = 92), galantamine (n = 33), or rivastigmine (n = 46) were enrolled. Response to treatment was quantified by grading the patient's cognitive state (Mini-Mental State Examination) and the patient's ability to perform normal daily activities (Activities of Daily Living, Instrumental Activities of Daily Living) at baseline and after 6 and 12 months of treatment. Genetic variation was comprehensively characterized and analyzed at two loci: CYP2D6, which is involved in donepezil and galantamine metabolism, and BCHE, which codes for an enzyme (butyrylcholinesterase) which is both target and metabolizer of rivastigmine. APOE (coding for apolipoprotein E), which is associated with the risk of AD and inefficacy of specific AD treatments, was genotyped to control for patient stratification. The influence of the CYP2D6 and BCHE genotype on clinical changes after 12 months was evaluated by several tests of association.
resultsAfter 1 year of treatment, 29, 12, and 12 of the patients receiving donepezil, galantamine, and rivastigmine, respectively, showed a cognitive decrement, while eight patients interrupted the therapy before 12 months of treatment. No significant differences between the three treatments were observed in terms of response and tolerability. Non-responders show a higher proportion of BCHE and CYP2D6 mutated alleles, but genetic variation at the two loci was not a reliable predictor of clinical changes in AD patients treated with cholinesterase inhibitors.
conclusionsIndividualized therapy based on CYP2D6 and BCHE genotypes is unlikely to be beneficial for treating Alzheimer's disease patients in routine clinical practice.
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