P1‐263: Secondary endpoint and responder analyses in a study of rosiglitazone XR in APOE4‐stratified subjects with mild‐to‐moderate Alzheimer's disease

Alderton, Claire; Zvartau-Hind, Marina; Ritchie, Sally Y.; Saunders, Ann M.; Craft, Suzanne; Landreth, Gary E.; Linnamägi, Ülla; Sawchak, Sharon; Gold, Michael

doi:10.1016/j.jalz.2009.04.271

Cited by 4 publications

(1 citation statement)

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“…It showed promising results in early AD [44], although only in carriers of apolipoprotein gene (APOE) ε4 allele in another study [45]. Preliminary results of a larger 6-month interventional trial in patients with mild to moderate AD were presented in International Congress of Alzheimer's Disease (ICAD) 2009; treatment with rosiglitazone showed no benefit in cognitive measures irrespectively of the APOE status [46].…”

Section: Diabetes and Cognitive Impairmentmentioning

confidence: 99%

The complex interplay of cardiovascular system and cognition: How to predict dementia in the elderly?

Kerola

Kettunen

Nieminen

2011

International Journal of Cardiology

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Section: Diabetes and Cognitive Impairmentmentioning

confidence: 99%

The complex interplay of cardiovascular system and cognition: How to predict dementia in the elderly?

Kerola

Kettunen

Nieminen

2011

International Journal of Cardiology

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Modeling Alzheimer's disease progression using the disease system analysis approach

Goméni

Simeoni

Zvartau-Hind

et al. 2011

Alzheimer's & Dementia

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A novel mechanistic model based on a disease system analysis paradigm was developed to explore the role of homeostatic mechanisms involved in Alzheimer's disease (AD) progression. We used longitudinal AD Assessment Scale-cognitive subscale (ADAS-cog) scores from 926 subjects with AD on stable acetylcholinesterase inhibitor therapy randomized to placebo treatment in two 54-week clinical trials. Alternative mechanistic models were evaluated by assuming that the rate of change of ADAS-cog over time was jointly regulated by a process characterizing the deterioration of ADAS-cog and by a process associated with a compensatory regulatory response. The model based on a time-varying deterioration rate of ADAS-cog performed better than the model based on a time-varying homeostatic control. The covariate analysis indicated that baseline Mini-Mental State Examination score, education, age, and apolipoprotein ɛ4 genotype had a significant effect on the level and shape of the trajectories of the mean model predicted ADAS-cog change from baseline.

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A Multi-Center Randomized Proof-of-Concept Clinical Trial Applying [18F]FDG-PET for Evaluation of Metabolic Therapy with Rosiglitazone XR in Mild to Moderate Alzheimer's Disease

Tzimopoulou

Cunningham

Nichols

et al. 2011

JAD

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Here we report the first multi-center clinical trial in Alzheimer's disease (AD) using fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) measures of brain glucose metabolism as the primary outcome. We contrasted effects of 12 months treatment with the PPARγ agonist Rosiglitazone XR versus placebo in 80 mild to moderate AD patients. Secondary objectives included testing for reduction in the progression of brain atrophy and improvement in cognition. Active treatment was associated with a sustained but not statistically significant trend from the first month for higher mean values in Kiindex and CMRgluindex, novel quantitative indices related to the combined forward rate constant for [18F]FDG uptake and to the rate of cerebral glucose utilization, respectively. However, neither these nor another analytical approach recently validated using data from the Alzheimer's Disease Neuroimaging Initiative indicated that active treatment decreased the progression of decline in brain glucose metabolism. Rates of brain atrophy were similar between active and placebo groups and measures of cognition also did not suggest clear group differences. Our study demonstrates the feasibility of using [18F]FDG-PET as part of a multi-center therapeutics trial. It suggests that Rosiglitazone is associated with an early increase in whole brain glucose metabolism, but not with any biological or clinical evidence for slowing progression over a 1 year follow up in the symptomatic stages of AD.

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P1‐263: Secondary endpoint and responder analyses in a study of rosiglitazone XR in APOE4‐stratified subjects with mild‐to‐moderate Alzheimer's disease

Cited by 4 publications

References 0 publications

The complex interplay of cardiovascular system and cognition: How to predict dementia in the elderly?

The complex interplay of cardiovascular system and cognition: How to predict dementia in the elderly?

Modeling Alzheimer's disease progression using the disease system analysis approach

A Multi-Center Randomized Proof-of-Concept Clinical Trial Applying [18F]FDG-PET for Evaluation of Metabolic Therapy with Rosiglitazone XR in Mild to Moderate Alzheimer's Disease

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