We propose to study whether regional cerebral blood flow (rCBF) imaging will give the same pattern of abnormalities in the brain as has been demonstrated by fluorodeoxyglucose (FDG) positron emission tomography (PET) studies in patients with Alzheimer-type dementia (ATD). PET studies will use the Donner 280 crystal tomograph and a new Donner 600 crystal (2.5-4mm resolution) tomograph with 15O-H2O to measure rCBF, 15O2 for oxygen utilization and 18F-FDG to measure metabolism. Single photon emission computed tomography (SPECT) studies will also be performed using a modification of the Harvard multidetector system and 123I-N-isopropyl-p-iodoamphetamine (IMP) to study rCBF. Subjects will be selected according to rigorous medical and neuropsychological research criteria and will include both familial and sporadic ATD. Since many subjects will be part of ongoing demential research using PET to study brain metabolism, a high rate of follow-up with low attrition is predicted, and a high rate of autopsy correlation is likely. Data will be analyzed quantitatively by comparing relative levels of activity in different brain regions for each patient and by calculation of rates of rCBF, regional cerebral metabolic rates of gluocse (rCMRglu), and regional cerebral metabolic rates of O2 (rCMRO2). It is hypothesized that patterns of abnormal rCBF will allow differentiation of dementia groups. In addition, we will analyze the data to examine correlations between rCBF and neuropsychological abnormalities, and to evaluate the SPECT-IMP method in comparison to PET studies. The major hypothesis is that the abnormalities seen in numerous investigations of cerebral metabolism in ATD will show similar abnormalities in rCBF. The SPECT studies will validate the use of IMP as a flow tracer in pathological tissue, and evaluate the ability of this lower cost imaging modality to differentiate dementia types. A basic medical science proposal includes the investigation of a flow-metabolism decoupling in early Alzheimer's disease, particularly in the temporal cortex. While we believe that flow-metabolism coupling will be shown to be grossly intact in the disease, we hypothesize that focal regions of flow-metabolism uncoupling will be demonstrable using the high resolution Donner 600 crystal tomograph. This finding will be of great importance for our understanding of the pathogenesis of Alzheimer's disease, as well as for planning therapeutic strategies.
| Maltz, Jonathan S; Budinger, Thomas F (2005) Evaluation of arterial endothelial function using transit times of artificially induced pulses. Physiol Meas 26:293-307 |
| Maltz, Jonathan S; Eberling, Jamie L; Jagust, William J et al. (2004) Enhanced cutaneous vascular response in AD subjects under donepezil therapy. Neurobiol Aging 25:475-81 |
