The main objective of this proposal is to demonstrate that the medial temporal lobe (hippocampus and parahippocampal gyrus) is specifically vulnerable to the effects of normal aging and is of fundamental importance in predicting age-related memory changes. Our preliminary studies have contributed to a greater understanding of the relationship between hippocampal integrity and cognitive functioning. We previously developed and replicated a CT diagnostic marker that predicts with 91% accuracy which non-demented, but minimally impaired individuals are likely to develop symptoms of Alzheimer's Disease (AD) within a 3 to 4-year interval. This subjectively assessed marker relies on increased CSF accumulation within the peri-hippocampal fissures as an indirect index of hippocampal atrophy and is referred to as HCSF. Our neuropathological studies of the hippocampal region in AD have validated the observation of HCSF as a marker of hippocampal atrophy. Preliminary MR volume studies have revealed both the anatomy and a potential anatomic specificity for these early hippocampal changes. In normal aging, we have shown that HCSF is associated with reduced memory performance. We now propose a 5 year NR project to collect longitudinal data on the clinical risks associated with direct parenchymal measures of hippocampal volume reduction (HVOL) among non-demented elderly. Salient hypotheses to be tested include: (l) HVOL is predictive of progressive memory changes in normal elderly, (2) HVOL predicts future lateral temporal lobe atrophy and (3) HVOL combined with lateral temporal lobe atrophy are necessary for the expression of the cognitive symptoms of AD. We propose a 5-year longitudinal study on 2 elderly groups, each n=100. These groups will be selected to represent the full range of cognitive functioning associated with normal aging as well as the full range of HVOL seen in non-demented elderly individuals. We will use a gradient echo MR procedure with good gray-white contrast in order to improve our current in vivo anatomic identification. The results from this study will improve our knowledge of the hippocampus and the prediction of cognitive decline in aging.
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