Quantitation, regional vulnerability, and kinetic modeling of brain glucose metabolism in mild Alzheimer's disease

Purpose To examine CMRglc measures and corresponding glucose transport (K-1 and k(2)) and phosphorylation (k(3)) rates in the medial temporal lobe (MTL, comprising the hippocampus and amygdala) and posterior cingulate cortex (PCC) in mild Alzheimer's disease (AD). Methods Dynamic FDG PET with arterial blood sampling was performed in seven mild AD patients (age 68 +/- 8 years, four females, median MMSE 23) and six normal (NL) elderly (age 69 +/- 9 years, three females, median MMSE 30). Absolute CMRglc (mu mol/100 g/min) was calculated from MRI-defined regions of interest using multiparametric analysis with individually fitted kinetic rate constants, Gjedde-Patlak plot, and Sokoloff's autoradiographic method with population-based rate constants. Relative ROI/pons CMRglc (unitless) was also examined. Results With all methods, AD patients showed significant CMRglc reductions in the hippocampus and PCC, and a trend towards reduced parietotemporal CMRglc, as compared with NL. Significant k(3) reductions were found in the hippocampus, PCC and amygdala. K-1 reductions were restricted to the hippocampus. Relative CMRglc had the largest effect sizes in separating AD from NL. However, the magnitude of CMRglc reductions was 1.2- to 1.9-fold greater with absolute than with relative measures. Conclusion CMRglc reductions are most prominent in the MTL and PCC in mild AD, as detected with both absolute and relative CMRglc measures. Results are discussed in terms of clinical and pharmaceutical applicability.