This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This study will attempt to identify the earliest predictors of memory and brain deterioration in preclinical Alzheimer's disease (AD) using FDG-PET. The hypothesis is that longitudinal reductions in glucose metabolism in the entorhinal cortex predict the onset of minimal cognitive impairment. Two groups of medically healthy elderly will be studied: one group will have evidence of memory decline. A third group will be normal healthy volunteers 20-30 years of age. For groups 1&2, clinical evaluations, a neuropsychological battery and Alzheimer's-associated cognitive deficits will be evaluated at baseline and at 36 months. PET and MRI will be performed at baseline and at 36 months to evaluate hippocampal pathology (MRI also at 18 months).Using this population, the following hypotheses will be tested: 1) Does enterorhinal cortex glucose metabolism predict decline in neuropsychological performance? 2) On the basis of observation of hyperglycemia-induced increase in glucose metabolism and memory in normal but not in AD, does decreased hippocampus glucose transport (evaluated under steady-state hyperglycemia and euglycemia) predict progressive brain deterioration? This study may help in the detection of subjects at risk for AD.
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