Tzimopoulou, Sofia, Cunningham, Vincent J., 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.

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 […]

Harrington, C., Sawchak, S., Chiang, C., Davies, J., Donovan, C., Saunders, A. M., Irizarry, M., Jeter, B., Zvartau-Hind, M., van Dyck, C. H., Gold, M.

Introduction: Two phase 3 studies evaluated the efficacy and safety of rosiglitazone (RSG), a type 2 diabetes treatment, in an extended release (RSG XR) form as adjunctive therapy to ongoing acetylcholine esterase inhibitor (AChEI) treatment in AD (REFLECT-2, adjunctive to donepezil; REFLECT-3, to any AChEI). An open-label extension study (REFLECT-4) assessed RSG XR long-term safety.; […]

Abbatecola, Angela M., Lattanzio, Fabrizia, Molinari, Anna M., Cioffi, Michele, Mansi, Luigi, Rambaldi, Pierfrancesco, DiCioccio, Luigi, Cacciapuoti, Federico, Canonico, Raffaele, Paolisso, Giuseppe

Objective: Studies have suggested that insulin resistance plays a role in cognitive impairment in individuals with type 2 diabetes. We aimed to determine whether an improvement in insulin resistance could explain cognitive performance variations over 36 weeks in older individuals with mild cognitive impairment (MCI) and type 2 diabetes.; Research Design and Methods: A total […]

Gold, Michael, Alderton, Claire, Zvartau-Hind, Marina, Egginton, Sally, Saunders, Ann M., Irizarry, Michael, Craft, Suzanne, Landreth, Gary, Linnamägi, Ulla, Sawchak, Sharon

Background/aims: A phase II study of the peroxisome proliferator-activated receptor-γ agonist rosiglitazone extended release (RSG XR) in mild-to-moderate Alzheimer’s disease (AD) detected a treatment benefit to cognition in apolipoprotein E(APOE)-ε4-negative subjects. The current phase III study with prospective stratification by APOE genotype was conducted to confirm the efficacy and safety of RSG XR in mild-to-moderate […]

Ng, Tze Pin, Feng, Liang, Yap, Keng Bee, Lee, Tih Shih, Tan, Chay Hoon, Winblad, Bengt

Evidence strongly supports the important role of insulin resistance in cognitive decline and dementia and suggests that insulin sensitizers may protect against cognitive decline in diabetic and pre-diabetic individuals. Inconclusive results have been reported in clinical trials of rosiglitazone, an insulin sensitizer that also increases cardiovascular mortality risks. No study has yet reported a protective […]