Diminished Glucose Transport in Alzheimer's Disease: Dynamic PET Studies

Dynamic positron emission tomography with [¹⁸F]fluorodeoxyglucose was used in six patients with Alzheimer's disease (AD) and seven healthy age-matched control subjects to estimate the kinetic parameters K₁*, k₂*, and k₃* that describe glucose transport and phosphorylation. A high-resolution tomograph was used to acquire brain uptake data in one tomographic plane, and a radial artery catheter connected to a plastic scintillator was used to acquire arterial input data. A nonlinear iterative least-squares fitting procedure that included terms for the vascular fraction and time delay to the peripheral sampling site was used to fit a three-compartment model to the brain data. Regions studied included frontal, temporal, occipital, and the entire cortex and subcortical white matter. The values obtained for the individual rate constants and regional CMR_glc (rCMR_glc; calculated using regional values of the rate constants) were higher than those reported previously. A significant (p < 0.05) decrease was found in K₁* in frontal and temporal cortex in the AD patients compared with the controls, with values of 0.157 and 0.161 ml/g/min in frontal and temporal cortex, respectively, of controls and 0.127 and 0.126 ml/ g/min in frontal and temporal cortex of the AD patients. rCMR_glc was also significantly (p < 0.02) lower in the AD patients than controls in all cortical brain regions. Lower values of k₃* were found in all brain regions in the AD patients, although these were not statistically significant. These findings provide evidence of an in vivo abnormality of forward glucose transport in AD. This transport defect, however, is probably not the cause of the diminution in glucose metabolism that has been widely found in AD patients, since a diminution of this magnitude should not lower intracerebral glucose content enough to alter rCMR_glc.