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Cited by 118Dementia and Cognitive Impairment ResearchCholinesterase and Neurodegenerative DiseasesAlzheimer's disease research and treatments

Chronic donepezil treatment is associated with slowed cognitive decline in Alzheimer's disease

Doody, R.S., Dunn, J.K., Clark, C.M., Farlow, M., Foster, N.L., Liao, T., Gonzales, N., Lai, E. +1 more·2001·Dementia and Geriatric Cognitive Disorders
DOI 10.1159/000051272
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Abstract

OBJECTIVE: To compare rates of cognitive decline between probable Alzheimer's disease (AD) patients treated with long-duration cholinesterase inhibitors (ChE-Is) and those who remained untreated. BACKGROUND: ChE-Is, including donepezil and tracrine, have shown beneficial effects on cognition and global functioning in patients with AD. The duration of these benefits is unknown because the longest double-blind placebo-controlled studies reported were only approximately 6 months long. Ethical concerns regarding randomization of patients to placebo for long periods make it difficult to undertake trials of longer duration. METHODS: We identified patients in 4 AD centers who were or were not consistently treated with ChE-Is and who had demographic, psychometric and follow-up data. We compared 205 ChE-I-treated and 218 untreated AD patients on baseline variables hypothesized to differ between these groups, on baseline Mini Mental Status Examination (MMSE) scores and on rates of MMSE change at 1 year. The analysis was performed initially with all ChE-I-treated patients as a single group versus untreated subjects, and then with donepezil versus untreated subjects and tacrine versus untreated subjects. RESULTS: As expected, treated and untreated patients differed with respect to age, education, ethnicity, percentage of community dwelling and exact days of follow-up (ANOVA and chi2) in several comparisons, but did not differ on baseline MMSE score. These baseline variables were highly intercorrelated. MMSE scores declined significantly more slowly after 1 year of ChE-I treatment compared to untreated patients (p = 0.05) after controlling for baseline differences in age, education, ethnicity and percentage of community dwelling. Slowing of decline was significant in the donepezil-treated patients (p = 0.007) but not in the tacrine-treated group (p = 0.33). CONCLUSIONS: This study, utilizing concurrent, nonrandomized controls, suggests that donepezil continues to have efficacy over at least the first year of therapy. Other studies are needed to determine whether the benefits are maintained beyond 1 year.

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Crossref · 10.1159/000051272

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  • Longer term benefits of cholinesterase inhibitors, from 2 to 4 or more years, have been demonstrated in open-label extension and long-term prospective observational clinical cohort studies.

    “Longer term benefits, from 2 to 4 or more years have been demonstrated in open-label extension 69,[88][89][90] and long-term prospective observational clinical cohort studies.[91][92][93][94][95]”

    From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [90]

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Authors
Doody, R. S., Dunn, J. K., Clark, C. M., Farlow, M., Foster, N. L., Liao, T., Gonzales, N., Lai, E., & Massman, P.
Affiliations
  • Baylor College of Medicine (US)
  • University of Pennsylvania (US)
  • Indiana University – Purdue University Indianapolis (US)
  • University of Michigan (US)
ORCID
Venue
Dementia and Geriatric Cognitive Disorders
Publisher
S. Karger AG
Published
2001
Volume
12
Issue
4
Pages
295-300
ISSN
  • 1420-8008 (ISSN-L)
  • 1421-9824
DOI
10.1159/000051272
OpenAlex
W2014978327
Cited by
118
References
18
Citations by year
2026: 3 · 2025: 2 · 2024: 4 · 2022: 5 · 2021: 1 · 2020: 5 · 2019: 6 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 9 · 2014: 7 · 2013: 7 · 2012: 1
FWCI
5.97
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Dementia and Geriatric Cognitive Disorders (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Eisai
  • Pfizer Pharmaceuticals
  • Division of Chemistry
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
donepezil, tacrine, cholinesterase inhibitors, Alzheimer's disease, cognitive decline, long-term drug efficacy, untreated patients, Mini-Mental State Examination
MeSH terms
Donepezil, Aged, Aged, 80 and over, Alzheimer Disease, Cholinesterase Inhibitors, Cognition, Female, Humans, Indans, Male, Mental Status Schedule, Middle Aged, Piperidines, Retrospective Studies, Tacrine, Treatment Outcome, Nootropic Agents

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