Effect of  ApoE  Genotype on Response to Donepezil in Patients with Alzheimer’s Disease

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Abstract

Background/Aims: The possible influence of apolipoprotein E (ApoE) genotype on the response to acetylcholinesterase inhibitor therapy in patients with Alzheimer’s disease (AD) remains a matter of controversy. In order to address this issue, we investigated the effects of ApoE genotype on the clinical response to donepezil in patients with mild to moderate AD. Methods: An open study was carried out in 51 patients with probable AD who were treated with 5–10 mg of donepezil per day for 48 weeks. Results: Eighteen (35.3%) of the 51 patients had 1 or 2 ApoE Ε 4 alleles. ApoE Ε 4 carriers with AD showed a mean 1.1-point increase from the baseline score of 23.9 on the 70-point Alzheimer’s Disease Assessment Scale-Cognitive Component at 48 weeks, while the ApoE Ε 4 noncarrier group showed a 3.1-point increase from the baseline score of 22.5 (p = 0.03). The ApoE Ε 4 carrier group exhibited a mean 0.13-point worsening from the baseline score of 0.97 on the Korean Instrumental Activities of Daily Living at 48 weeks, while the ApoE Ε 4 noncarrier group exhibited a 0.17-point worsening from the baseline score of 0.64 (p = 0.05). Conclusion: AD patients who carry the ApoE Ε 4 allele may respond more favorably to donepezil than Ε 4 noncarriers.

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Vitamin E and donepezil for the treatment of mild cognitive impairment.

Ronald Petersen, Ronald Thomas, Michael Grundman … (2005)

Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer's disease. In a double-blind study, we evaluated subjects with the amnestic subtype of mild cognitive impairment. Subjects were randomly assigned to receive 2000 IU of vitamin E daily, 10 mg of donepezil daily, or placebo for three years. The primary outcome was clinically possible or probable Alzheimer's disease; secondary outcomes were cognition and function. A total of 769 subjects were enrolled, and possible or probable Alzheimer's disease developed in 212. The overall rate of progression from mild cognitive impairment to Alzheimer's disease was 16 percent per year. As compared with the placebo group, there were no significant differences in the probability of progression to Alzheimer's disease in the vitamin E group (hazard ratio, 1.02; 95 percent confidence interval, 0.74 to 1.41; P=0.91) or the donepezil group (hazard ratio, 0.80; 95 percent confidence interval, 0.57 to 1.13; P=0.42) during the three years of treatment. Prespecified analyses of the treatment effects at 6-month intervals showed that as compared with the placebo group, the donepezil group had a reduced likelihood of progression to Alzheimer's disease during the first 12 months of the study (P=0.04), a finding supported by the secondary outcome measures. Among carriers of one or more apolipoprotein E epsilon4 alleles, the benefit of donepezil was evident throughout the three-year follow-up. There were no significant differences in the rate of progression to Alzheimer's disease between the vitamin E and placebo groups at any point, either among all patients or among apolipoprotein E epsilon4 carriers. Vitamin E had no benefit in patients with mild cognitive impairment. Although donepezil therapy was associated with a lower rate of progression to Alzheimer's disease during the first 12 months of treatment, the rate of progression to Alzheimer's disease after three years was not lower among patients treated with donepezil than among those given placebo. Copyright 2005 Massachusetts Medical Society.

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Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer's disease. Alzheimer's Disease Centers Consortium on Apolipoprotein E and Alzheimer's Disease.

William Evans, C Phelps, S S Mirra … (1998)

The epsilon4 allele of the gene encoding apolipoprotein E (APOE) is strongly associated with Alzheimer's disease, but its value in the diagnosis remains uncertain. We reviewed clinical diagnoses and diagnoses obtained at autopsy in 2188 patients referred to 1 of 26 Alzheimer's disease centers for evaluation of dementia. The sensitivity and specificity of the clinical diagnosis or the presence of an APOE epsilon4 allele were calculated, with pathologically confirmed Alzheimer's disease used as the standard. The added value of the APOE genotype was estimated with pretest and post-test probabilities from multivariate analyses to generate receiver-operating-characteristic curves plotting sensitivity against the false positive rate. Of the 2188 patients, 1833 were given a clinical diagnosis of Alzheimer's disease, and the diagnosis was confirmed pathologically in 1770 patients at autopsy. Sixty-two percent of patients with clinically diagnosed Alzheimer's disease, as compared with 65 percent of those with pathologically confirmed Alzheimer's disease, had at least one APOE epsilon4 allele. The sensitivity of the clinical diagnosis was 93 percent, and the specificity was 55 percent, whereas the sensitivity and specificity of the APOE epsilon4 allele were 65 and 68 percent, respectively. The addition of information about the APOE genotype increased the overall specificity to 84 percent in patients who met the clinical criteria for Alzheimer's disease, although the sensitivity decreased. The improvement in specificity remained statistically significant in the multivariate analysis after adjustment for differences in age, clinical diagnosis, sex, and center. APOE genotyping does not provide sufficient sensitivity or specificity to be used alone as a diagnostic test for Alzheimer's disease, but when used in combination with clinical criteria, it improves the specificity of the diagnosis.

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Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors

J Growdon, B. Slack, R Wurtman … (1992)

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Author and article information

Journal

Journal ID (publisher-id): DEM

Journal ID (nlm-ta): Dement Geriatr Cogn Disord

Journal ID (doi): 10.1159/issn.1420-8008

Title: Dementia and Geriatric Cognitive Disorders

Publisher: S. Karger AG

ISSN (Print): 1420-8008

ISSN (Electronic): 1421-9824

Publication date Subscription-year: 2008

Publication date (Print): April 2008

Publication date (Electronic): 10 April 2008

Volume: 25

Issue: 5

Pages: 445-450

Affiliations

^aDepartment of Neurology, Inha University College of Medicine, Incheon, ^bDepartment of Neurology, Bobath Memorial Hospital, Seongnam, ^cDepartment of Neurology, Seoul National University College of Medicine, ^dDepartment of Neurology, Eulji University School of Medicine, and ^eDepartment of Neurology, Catholic University of Korea College of Medicine, Seoul, ^fDepartment of Neurology, Changwon Fatima Hospital, Changwon, and ^gDepartment of Neurology, Yeungnam University College of Medicine, Daegu, South Korea

Article

Publisher ID: 124752 Other ID: Dement Geriatr Cogn Disord 2008;25:445–450

DOI: 10.1159/000124752

PubMed ID: 18401173

SO-VID: 5adb2ebb-fafc-4aa9-82a0-4e854ac3faf3

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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

History

Date accepted : 24 January 2008

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Figures: 1, Tables: 2, References: 30, Pages: 6

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Effect of ApoE Genotype on Response to Donepezil in Patients with Alzheimer’s Disease

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Karger: Neurology and Neuroscience

Most cited references 15

Vitamin E and donepezil for the treatment of mild cognitive impairment.

Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer's disease. Alzheimer's Disease Centers Consortium on Apolipoprotein E and Alzheimer's Disease.

Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors

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