Predictive Factors of Clinical Response to Cholinesterase Inhibitors in Mild and Moderate Alzheimer's Disease and Mixed Dementia: A One-Year Naturalistic Study

Miranda, Luís Felipe José Ravic de; Gomes, Karina Braga; Silveira, Josianne Nicácio; Pianetti, Gérson Antônio; Byrro, Ricardo Martins Duarte; Peles, Patrícia Regina Henrique; Pereira, Fernando Henrique; Santos, Thiago Rezende dos; Assini, Arthur G.; Ribeiro, Valéria V.; Tito, Pedro Augusto Lopes; Matoso, Rafael O; Lima, Thiago Oliveira Lemos de; Moraes, Edgar Nunes de; Caramelli, Paulo

doi:10.3233/jad-142148

Cited by 31 publications

(23 citation statements)

References 22 publications

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“…Some limitations in the present study may be considered, such as the small sample size and the fact that five patients (10%) taking donepezil abandoned the treatment because of side effects, although this rate was not above the rates found in patients from our sample who took other ChEIs [22]. The study population is very old (19 out of 42 patients were aged 82+ years) and with low educational level (35 out of 42 patients had less than 4 years of education).…”

Section: Discussioncontrasting

confidence: 56%

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Clinical Response to Donepezil in Mild and Moderate Dementia: Relationship to Drug Plasma Concentration and CYP2D6 and APOE Genetic Polymorphisms

Miranda

Gomes

Tito

et al. 2016

JAD

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The clinical response to donepezil in patients with mild and moderate dementia was investigated in relation to the drug plasma concentration and APOE and CYP2D6 polymorphisms. In a prospective naturalistic observational study, 42 patients with Alzheimer's disease (AD) and AD with cerebrovascular disease who took donepezil (10 mg) for 12 months were evaluated. Their DNA was genotyped, and the donepezil plasma concentrations were measured after 3, 6, and 12 months. Good responders scored ≥-1 on the Mini-Mental State Examination at 12 months in comparison to the baseline score. The study results indicated the good response pattern was influenced by the concentration of donepezil, but not by APOE and CYP2D6 polymorphisms.

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Section: Discussioncontrasting

confidence: 56%

“…The clinical and genetic (APOE and CYP2D6) protocols for the study have been described in detail previously [22].…”

Section: Clinical and Laboratory Assessmentsmentioning

confidence: 99%

Clinical Response to Donepezil in Mild and Moderate Dementia: Relationship to Drug Plasma Concentration and CYP2D6 and APOE Genetic Polymorphisms

Miranda

Gomes

Tito

et al. 2016

JAD

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“…Хороший клинический эффект от приема 10 мг донепезила (снижение по шкале MMSE не более чем на 1 балл за 12 мес) коррелировал с более высокой концентрацией препарата в плазме крови, но не с полиморфизмом CYP2D6. Eще в одном исследовании этих авторов [20] были обследованы 97 пациентов с БА, которые в течение 12 мес получали один из трех ингибиторов холинэстеразы. Было выявлено, что у пациентов, хорошо ответивших на лечение спустя 3 мес от начала приема препарата, этот эффект сохранялся и спустя 12 мес.…”

Section: Discussionunclassified

Is it personalized treatment of dementia based on the CYP2D6 gene polymorphism possible?

Chebotareva

Левин

Markov

et al. 2018

Z. nevrol. psikhiatr. im. S.S. Korsakova

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Лечение деменции является одной из актуальных проблем современной неврологии. Применяемые в клинической практике антидементные препараты в части случаев оказываются неэффективными либо вызывают неприемлемые нежелательные явления. В рамках концепции персонализированного подхода к терапии ведется активный поиск предикторов эффективности и безопасности лечения у конкретного больного. Примерно 15-20% пациентам с болезнью Альцгеймера (БА) в силу особенностей фармакогенетики требуется применение ингибиторов холинэстеразы в дозах препарата, отличающихся от указанных в инструкции. Одна часть таких больных

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“…The most common ABCB1 haplotypes were 1236C/2677G/3435C (46%) and 1236T/2677T/3435T (41%), and patients homo zygous for the T/T/T haplotype had lower plasma donepezil concentrationtodose ratios and better clin ical response than patients with other genotypes [66]. In Brazilian patients treated with AChEIs, the response rate was 27.8%, with no apparent effect of APOE and/or CYP2D6 polymorphic variants [67].…”

Section: Pathogenic Genesmentioning

confidence: 98%

Pharmacogenetic Considerations in the Treatment of Alzheimer’s Disease

et al. 2016

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The practical pharmacogenetics of Alzheimer's disease (AD) is circumscribed to acetylcholinesterase inhibitors (AChEIs) and memantine. However, pharmacogenetic procedures should be applied to novel strategies in AD therapeutics including: novel AChEIs and neurotransmitter regulators, anti-Aβ treatments, anti-tau treatments, pleiotropic products, epigenetic drugs and combination therapies. Genes involved in the pharmacogenetic network are under the influence of the epigenetic machinery which regulates gene expression transcriptionally and post-transcriptionally, configuring the fundamentals of pharmacoepigenomics. Over 60% of AD patients present concomitant pathologies demanding additional treatments which increase the likelihood of drug-drug interactions. Lipid metabolism dysfunction is a pathogenic mechanism inherent to AD neurodegeneration. The therapeutic response to hypolipidemic compounds is influenced by the APOE and CYP genotypes. The development of novel compounds and the use of combination/multifactorial treatments require the implantation of pharmacogenomic procedures for the avoidance of ADRs and the optimization of therapeutics.

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Predictive Factors of Clinical Response to Cholinesterase Inhibitors in Mild and Moderate Alzheimer's Disease and Mixed Dementia: A One-Year Naturalistic Study

Abstract: A higher rate of good response was observed in this study compared to that in previous investigations. The pharmacogenetic aspects do not seem to have an influence in the response.

Cited by 31 publications

References 22 publications

Clinical Response to Donepezil in Mild and Moderate Dementia: Relationship to Drug Plasma Concentration and CYP2D6 and APOE Genetic Polymorphisms

Clinical Response to Donepezil in Mild and Moderate Dementia: Relationship to Drug Plasma Concentration and CYP2D6 and APOE Genetic Polymorphisms

Is it personalized treatment of dementia based on the CYP2D6 gene polymorphism possible?

Pharmacogenetic Considerations in the Treatment of Alzheimer’s Disease

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