This multicenter study examined 18 F-FDG PET measures in the differential diagnosis of Alzheimer's disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB) from normal aging and from each other and the relation of disease-specific patterns to mild cognitive impairment (MCI). Methods: We examined the 18 F-FDG PET scans of 548 subjects, including 110 healthy elderly individuals (''normals'' or NLs), 114 MCI, 199 AD, 98 FTD, and 27 DLB patients, collected at 7 participating centers. Individual PET scans were Z scored using automated voxelbased comparison with generation of disease-specific patterns of cortical and hippocampal 18 F-FDG uptake that were then applied to characterize MCI. Results: Standardized diseasespecific PET patterns were developed that correctly classified 95% AD, 92% DLB, 94% FTD, and 94% NL. MCI patients showed primarily posterior cingulate cortex and hippocampal hypometabolism (81%), whereas neocortical abnormalities varied according to neuropsychological profiles. An AD PET pattern was observed in 79% MCI with deficits in multiple cognitive domains and 31% amnesic MCI. 18 F-FDG PET heterogeneity in MCI with nonmemory deficits ranged from absent hypometabolism to FTD and DLB PET patterns. Conclusion: Standardized automated analysis of 18 F-FDG PET scans may provide an objective and sensitive support to the clinical diagnosis in early dementia.

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SUMMARY Hypoxia is a universal driver of aggressive tumor behavior, but the underlying mechanisms are not completely understood. Using a phosphoproteomics screen, we now show that active Akt accumulates in the mitochondria during hypoxia and phosphorylates pyruvate dehydrogenase kinase 1 (PDK1) on Thr346 to inactivate the pyruvate dehydrogenase complex. In turn, this pathway switches tumor metabolism towards glycolysis, antagonizes apoptosis and autophagy, dampens oxidative stress, and maintains tumor cell proliferation in the face of severe hypoxia. Mitochondrial Akt-PDK1 signaling correlates with unfavorable prognostic markers and shorter survival in glioma patients and may provide an “actionable” therapeutic target in cancer.

Local cerebral blood flow was measured in the mouse by means of the [14C]iodoantipyrine method. This method has been previously used in the monkey, dog, cat, and rat, but its application to small mammals such as the mouse requires special attention to potential sources of error. The small size of the mouse brain requires special attention to the rapid removal and freezing of the brain to minimize effects of postmortem diffusion of tracer in the tissue. Because of the relatively low diameter/length ratios of the catheters needed for arterial sampling in small animals, substantial errors can occur in the determination of the time course of the [14C]iodoantipyrine concentration in the arterial blood unless corrections for lag time and dead space washout in the catheter are properly applied. Local cerebral blood flow was measured in seven awake mice with appropriate care to minimize these sources of error. The values were found to vary from 48 ml/100 g/min in the corpus callosum to 198 ml/100 g/min in the inferior colliculus. The results demonstrate that the [14C]iodoantipyrine method can be used to measure local cerebral blood flow in the mouse and that the values in that species are, in general, somewhat higher than those in the rat.

Among clinicians who use positron emission tomography (PET), the standardized uptake value (SUV) is a popular semi-quantitative value that can be easily assessed whenever a PET study is performed under physiological and pathological conditions. It provides an index of regional tracer uptake normalized to the administered dose of tracer. The simplicity of SUV assessment contrasts with the complexity of full quantitative procedures requiring blood sampling and possibly dynamic scanning, which limits patient throughput and significantly increases the workload of a PET centre. Two main clinical conditions/variables affect the significance and usefulness of the SUV: the type and stage of the disease being assessed. Diagnosis, prognosis and therapy monitoring represent the possible uses of SUV. In the above clinical conditions an SUV may provide information about the single lesion in which it is assessed, but the utility of such information depends largely on its integration with all the available clinical and instrumental data.