Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer’s disease

Risner, M E; Saunders, A M; Altman, J F B; Ormandy, G C; Craft, S; Foley, I M; Zvartau-Hind, M E; Hosford, D A; Roses, A D; for the Rosiglitazone in Alzheimer's Disease Study Group

doi:10.1038/sj.tpj.6500369

Cited by 686Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchCholinesterase and Neurodegenerative Diseases

Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer’s disease

Risner, M E, Saunders, A M, Altman, J F B, Ormandy, G C, Craft, S, Foley, I M, Zvartau-Hind, M E, Hosford, D A +2 more·2006·The Pharmacogenomics Journal

DOI 10.1038/sj.tpj.6500369

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Abstract

Mild-to-moderate AD patients were randomized to placebo or rosiglitazone (RSG) 2, 4 or 8 mg. Primary end points at Week 24 were mean change from baseline in AD Assessment Scale-Cognitive (ADAS-Cog) and Clinician's Interview-Based Impression of Change Plus Caregiver Input global scores in the intention-to-treat population (N=511), and results were also stratified by apolipoprotein E (APOE) genotype (n=323). No statistically significant differences on primary end points were detected between placebo and any RSG dose. There was a significant interaction between APOE epsilon4 allele status and ADAS-Cog (P=0.014). Exploratory analyses demonstrated significant improvement in ADAS-Cog in APOE epsilon4-negative patients on 8 mg RSG (P=0.024; not corrected for multiplicity). APOE epsilon4-positive patients did not show improvement and showed a decline at the lowest RSG dose (P=0.012; not corrected for multiplicity). Exploratory analyses suggested that APOE epsilon4 non-carriers exhibited cognitive and functional improvement in response to RSG, whereas APOE epsilon4 allele carriers showed no improvement and some decline was noted. These preliminary findings require confirmation in appropriate clinical studies.

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From Metformin in Amnestic Mild Cognitive Impairment: Results of a Pilot Randomized Placebo Controlled Clinical Trial (2016) · cites this paper as [68]
One trial found rosiglitazone was effective in memory and attention, but another randomized placebo controlled trial and a Phase III trial failed to demonstrate its effectiveness in cognitive function.
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Trials have failed to demonstrate thiazolidinedione effectiveness in dementia patients' cognitive function, probably due to adverse cardiovascular effects outweighing potential benefits.
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From Type 2 Diabetes and Antidiabetic Medications in Relation to Dementia Diagnosis (2014) · cites this paper as [19]

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Authors: Risner, M. E., Saunders, A. M., Altman, J. F. B., Ormandy, G. C., Craft, S., Foley, I. M., Zvartau-Hind, M. E., Hosford, D. A., Roses, A. D., & for the Rosiglitazone in Alzheimer's Disease Study Group
Affiliations: GlaxoSmithKline (United States) (US)
GlaxoSmithKline (United Kingdom) (GB)
University of Washington (US)
Corresponding author: Risner, M E
ORCID: Saunders, A M
Craft, S
Venue: The Pharmacogenomics Journal
Publisher: Springer Science and Business Media LLC
Published: 2006-01-31
Volume: 6
Issue: 4
Pages: 246-254
ISSN: 1470-269X (ISSN-L)
1473-1150
DOI: 10.1038/sj.tpj.6500369
OpenAlex: W2099271519
Cited by: 686
References: 44
Citations by year: 2026: 9 · 2025: 17 · 2024: 20 · 2023: 22 · 2022: 18 · 2021: 21 · 2020: 29 · 2019: 29 · 2018: 22 · 2017: 25 · 2016: 28 · 2015: 36 · 2014: 43 · 2013: 25 · 2012: 42
FWCI: 39.11
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: The Pharmacogenomics Journal (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Keywords: rosiglitazone, Alzheimer's disease, apolipoprotein E, APOE ε4, genetic stratification, thiazolidinediones, cognitive function, functional decline, ADAS-Cog, pharmacogenomics, drug efficacy
MeSH terms: Rosiglitazone, Aged, Alleles, Alzheimer Disease, Apolipoproteins E, Cognition, Dose-Response Relationship, Drug, Female, Genotype, Humans, Hypoglycemic Agents, Male, Pharmacogenetics, Thiazolidinediones, Apolipoprotein E4

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Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer’s disease

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