The aim of this proposal is to study regional cerebral blood flow (rCBF) in Alzheimer's dementia (AD), and to relate rCBF to regional cerebral metabolic rate for glucose (rCMR) with positron emission tomography (PET) using our new 2.5 mm resolution PET system. Under the previous grant award a xenon-122 (t1/2 20h) generator was built which provides positron-emitting iodine-122 (t1/2 3.6 min) used for PET rCRF studies. The xenon-122 can be shipped from a distant cyclotron to provide iodine-122 regularly for several days. A new iodinated I-122 amphetamine (IDNNA) was developed and it is an extracted rCBF tracer. This will be validated by comparison to labeled microspheres in animals. In our laboratory we have found marked parietal-temporal deficits of rCMR in AD, using fluorine-18 fluorodeoxyglucose (FDG). With I-122 IDNNA a rCBF measurement can be followed in 20 min by fluorine-18 FDG to measure rCMR in the same patient. We propose to study rCBF and rCMR in patients with these disorders, and to determine whether these two functions are coupled in the affected brain areas. If they are coupled, the previously observed rCMR changes can also be measured using the much faster and simpler I-122 IDNNA rCBF tracer. If they are not coupled, this will provide important data on the neurophysiology of AD. By studying AD patients at varying stages of the disease we will test the hypothesis derived from work of others that the parieto-temporal hypometabolism may be caused by a cholinergically mediated deficit in rCBF. The new 2.5 mm resolution PET machine will enable us to look for changes in rCMR and rCBF with much finer detail than previously possible. This new rCBF tracer has potential for research applications in which it may be juxtaposed to tracer studies of other brain functions with PET to provide concomitant brain blood flow information.
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