| Authors | Tzimopoulou, S., Cunningham, V.J., Nichols, T.E., Searle, G., Bird, N.P., Mistry, P., Dixon, I.J., Hallett, W.A., Whitcher, B., Brown, A.P., Zvartau-Hind, M., Lotay, N., Lai, R.Y.K., Castiglia, M., Jeter, B., Matthews, J.C., Chen, K., Bandy, D., Reiman, E.M., Gold, M., Rabiner, E.A. and Matthews, P.M. |
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| Abstract | Here we describe methods for application of quantitative fluorodeoxyglucose positron emission tomography ([ 18F]FDG-PET) measures of brain glucose metabolism in multi-centre clinical trials for Alzheimer's disease. We validated methods and demonstrated their use in the context of a treatment trial with the PPARγ agonist Rosiglitazone XR versus placebo in mild to moderate AD patients. Novel quantitative indices related to the combined forward rate constant for [ 18F]FDG uptake \(({K}-{i}^{index})\) and to the rate of cerebral glucose utilization \((CM{R}-{glu}^{index})\) were applied. Active treatment was associated with a sustained but not statistically significant trend from the first month for higher mean values in both. However, neither these nor another analytical approach recently validated using data from the Alzheimer's Disease Neuroimaging Initiative suggested 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 demonstrate clear group differences. Our study demonstrates the feasibility of using [ 18F]FDG-PET as part of a multi-centre therapeutics trial and describes new measures that can be employed. It suggests that Rosiglitazone is associated with an early increase in whole brain glucose utilisation, but not with any biological or clinical evidence for slowing progression over the period of study in the selected patient group. |
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