Article

Effect of a CYP2D6 polymorphism on the efficacy of donepezil in patients with Alzheimer disease.

Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, 71013 San Giovanni Rotondo (FG), Italy.
Neurology (impact factor: 8.31). 10/2009; 73(10):761-7. DOI:10.1212/WNL.0b013e3181b6bbe3 pp.761-7
Source: PubMed

ABSTRACT To evaluate the influence of the single nucleotide polymorphism rs1080985 in the cytochrome P450 2D6 (CYP2D6) gene on the efficacy of donepezil in patients with mild to moderate Alzheimer disease (AD).
This was a multicenter, prospective cohort study of 127 white patients with AD according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association Work Group criteria. Patients were treated with donepezil 5-10 mg/daily for 6 months. Cognitive and functional statuses were evaluated at baseline and at 6-month follow-up. Response to therapy was defined according to the National Institute for Health and Clinical Excellence criteria. Compliance and drug-related adverse events were also evaluated. The analyses identifying the CYP2D6 and APOE polymorphisms were performed in blinded fashion.
At 6-month follow-up, 69 of 115 patients (60%) were responders and 46 patients (40%) were nonresponders to donepezil treatment. A significantly higher frequency of patients with the G allele of rs1080985 was found in nonresponders than in responders (58.7% vs 34.8%, p = 0.013). Logistic regression analysis adjusted for age, sex, Mini-Mental State Examination score at baseline, and APOE demonstrated that patients with the G allele had a significantly higher risk of poor response to donepezil treatment (odds ratio 3.431, 95% confidence interval 1.490-7.901).
The single nucleotide polymorphism rs1080985 in the CYP2D6 gene may influence the clinical efficacy of donepezil in patients with mild to moderate Alzheimer disease (AD). The analysis of CYP2D6 genotypes may be useful in identifying subgroups of patients with AD who have different clinical responses to donepezil.

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  • Article: Current concepts in mild cognitive impairment.
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Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

127 white patients
 
46 patients
 
APOE polymorphisms
 
clinical efficacy
 
Clinical Excellence criteria
 
Communicative Disorders
 
CYP2D6 gene
 
CYP2D6 genotypes
 
drug-related adverse events
 
G allele
 
higher frequency
 
higher risk
 
Mini-Mental State Examination score
 
moderate Alzheimer disease
 
poor response
 
prospective cohort study
 
Related Disorders Association Work Group criteria
 
single nucleotide polymorphism rs1080985
 
Stroke-Alzheimer's Disease
 
subgroups