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

Sofia Tzimopoulou, Vincent Joseph Cunningham, Thomas E. Nichols, Graham Searle, Nick P. Bird, Prafull Mistry, Ian J. Dixon, William A. Hallett, Brandon Whitcher, Andrew P. Brown, Marina Zvartau-Hind, Narinder Lotay, Robert Y. K. Lai, Mary Castiglia, Barbara Jeter, Julian C. Matthews, Kewei Chen, Dan Bandy, Eric M. Reiman, Michael Gold & 2 others Eugenii A. Rabiner, Paul M. Matthews

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Here we report the first multi-center clinical trial in Alzheimer's disease (AD) using fluorodeoxyglucose positron emission tomography ([F-18]FDG-PET) measures of brain glucose metabolism as the primary outcome. We contrasted effects of 12 months treatment with the PPAR gamma 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 K-i(index) and CMRgluindex, novel quantitative indices related to the combined forward rate constant for [F-18]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 [F-18]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.

Original languageEnglish
Pages (from-to)1241-1256
Number of pages16
JournalJournal of Alzheimer's Disease
Volume22
Issue number4
DOIs
Publication statusPublished - 2010

Keywords

  • F-18-FDG
  • Alzheimer's disease
  • analysis
  • dementia
  • PPAR gamma
  • rosiglitazone
  • positron-emission-tomography
  • cerebral glucose-metabolism
  • activated-receptor-gamma
  • blood-brain-barrier
  • apolipoprotein-E
  • cognitive impairment
  • diabetic-rats
  • genetic-risk
  • FDG-PET
  • insulin

Cite this

A Multi-Center Randomized Proof-of-Concept Clinical Trial Applying [F-18]FDG-PET for Evaluation of Metabolic Therapy with Rosiglitazone XR in Mild to Moderate Alzheimer's Disease. / Tzimopoulou, Sofia; Cunningham, Vincent Joseph; Nichols, Thomas E.; Searle, Graham; Bird, Nick P.; Mistry, Prafull; Dixon, Ian J.; Hallett, William A.; Whitcher, Brandon; Brown, Andrew P.; Zvartau-Hind, Marina; Lotay, Narinder; Lai, Robert Y. K.; Castiglia, Mary; Jeter, Barbara; Matthews, Julian C.; Chen, Kewei; Bandy, Dan; Reiman, Eric M.; Gold, Michael; Rabiner, Eugenii A.; Matthews, Paul M.

In: Journal of Alzheimer's Disease, Vol. 22, No. 4, 2010, p. 1241-1256.

Research output: Contribution to journalArticle

Tzimopoulou, S, Cunningham, VJ, Nichols, TE, Searle, G, Bird, NP, Mistry, P, Dixon, IJ, Hallett, WA, Whitcher, B, Brown, AP, Zvartau-Hind, M, Lotay, N, Lai, RYK, Castiglia, M, Jeter, B, Matthews, JC, Chen, K, Bandy, D, Reiman, EM, Gold, M, Rabiner, EA & Matthews, PM 2010, 'A Multi-Center Randomized Proof-of-Concept Clinical Trial Applying [F-18]FDG-PET for Evaluation of Metabolic Therapy with Rosiglitazone XR in Mild to Moderate Alzheimer's Disease' Journal of Alzheimer's Disease, vol. 22, no. 4, pp. 1241-1256. https://doi.org/10.3233/JAD-2010-100939
Tzimopoulou, Sofia ; Cunningham, Vincent Joseph ; Nichols, Thomas E. ; Searle, Graham ; Bird, Nick P. ; Mistry, Prafull ; Dixon, Ian J. ; Hallett, William A. ; Whitcher, Brandon ; Brown, Andrew P. ; Zvartau-Hind, Marina ; Lotay, Narinder ; Lai, Robert Y. K. ; Castiglia, Mary ; Jeter, Barbara ; Matthews, Julian C. ; Chen, Kewei ; Bandy, Dan ; Reiman, Eric M. ; Gold, Michael ; Rabiner, Eugenii A. ; Matthews, Paul M. / A Multi-Center Randomized Proof-of-Concept Clinical Trial Applying [F-18]FDG-PET for Evaluation of Metabolic Therapy with Rosiglitazone XR in Mild to Moderate Alzheimer's Disease. In: Journal of Alzheimer's Disease. 2010 ; Vol. 22, No. 4. pp. 1241-1256.
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N2 - Here we report the first multi-center clinical trial in Alzheimer's disease (AD) using fluorodeoxyglucose positron emission tomography ([F-18]FDG-PET) measures of brain glucose metabolism as the primary outcome. We contrasted effects of 12 months treatment with the PPAR gamma 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 K-i(index) and CMRgluindex, novel quantitative indices related to the combined forward rate constant for [F-18]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 [F-18]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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KW - cognitive impairment

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