Trial reportAlzheimer's research & therapy2023
Differential response to donepezil in MRI subtypes of mild cognitive impairment.
Trial report in Alzheimer's research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT00403520 (Assessment of the Comparative Effect of Donepezil 10mg/d and Placebo on Clinical and Radiological Markers in Patients With Mild Cognitive Disorders), which is not on this map. Cited by 13 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Assessment of the Comparative Effect of Donepezil 10mg/d and Placebo on Clinical and Radiological Markers in Patients With Mild Cognitive Disorders
Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Advances in gait research related to Alzheimer's disease.Frontiers in neurology · 2025Pooled it
- Brain patterns and risk factors in the FINGER RCT multimodal lifestyle intervention.The journal of prevention of Alzheimer's disease · 2025Trial
- Dynamic long-term modulation of cognition, brain structure and covariance networks in mild cognitive impairment due to AD by donepezil: A 36-month longitudinal study.Journal of neurology · 2026Article
- Co-pathologies and biological processes beyond amyloid-beta and tau in people with Alzheimer's disease: Evidence from clinical cohort studies.Journal of internal medicine · 2026Review
- Donepezil Research in Cognitive Impairment: A Bibliometric and Scientometric Analysis of Global Trends and Pharmacological Perspectives.Brain and behavior · 2026Article
- Detecting limbic predominant neurodegenerative co-pathologies in vivo in Alzheimer's disease: magnetic resonance imaging markers, cognitive correlates, and prognosis.Alzheimer's research & therapy · 2025Article
- Revealing heterogeneity in mild cognitive impairment based on individualized structural covariance network.Alzheimer's research & therapy · 2025Article
- Alzheimer-typical temporo-parietal atrophy and hypoperfusion are associated with a more significant cholinergic impairment in amnestic neurodegenerative syndromes.Journal of Alzheimer's disease : JAD · 2025Article
- Pathologic subtyping of Alzheimer's disease brain tissue reveals disease heterogeneity.medRxiv : the preprint server for health sciences · 2024Article
- Review
- Adverse event profile of memantine and donepezil combination therapy: a real-world pharmacovigilance analysis based on FDA adverse event reporting system (FAERS) data from 2004 to 2023.Frontiers in pharmacology · 2024Article
- Multi-pathological contributions toward atrophy patterns in the Alzheimer's disease continuum.Frontiers in neuroscience · 2024Article
- Correction: Differential response to donepezil in MRI subtypes of mild cognitive impairment.Alzheimer's research & therapy · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 7 institutions in 5 countries.
Funding
Abstract
backgroundDonepezil is an approved therapy for the treatment of Alzheimer's disease (AD). Results across clinical trials have been inconsistent, which may be explained by design-methodological issues, the pathophysiological heterogeneity of AD, and diversity of included study participants. We investigated whether response to donepezil differs in mild cognitive impaired (MCI) individuals demonstrating different magnetic resonance imaging (MRI) subtypes.
methodsFrom the Hippocampus Study double-blind, randomized clinical trial, we included 173 MCI individuals (donepezil = 83; placebo = 90) with structural MRI data, at baseline and at clinical follow-up assessments (6-12-month). Efficacy outcomes were the annualized percentage change (APC) in hippocampal, ventricular, and total grey matter volumes, as well as in the AD cortical thickness signature. Participants were classified into MRI subtypes as typical AD, limbic-predominant, hippocampal-sparing, or minimal atrophy at baseline. We primarily applied a subtyping approach based on continuous scale of two subtyping dimensions. We also used the conventional categorical subtyping approach for comparison.
resultsDonepezil-treated MCI individuals showed slower atrophy rates compared to the placebo group, but only if they belonged to the minimal atrophy or hippocampal-sparing subtypes. Importantly, only the continuous subtyping approach, but not the conventional categorical approach, captured this differential response.
conclusionsOur data suggest that individuals with MCI, with hippocampal-sparing or minimal atrophy subtype, may have improved benefit from donepezil, as compared with MCI individuals with typical or limbic-predominant patterns of atrophy. The newly proposed continuous subtyping approach may have advantages compared to the conventional categorical approach. Future research is warranted to demonstrate the potential of subtype stratification for disease prognosis and response to treatment.
trial registrationClinicalTrial.gov NCT00403520. Submission Date: November 21, 2006.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.