This is a K23 Mentored Patient Oriented Career Development Award Application. The primary goal of the proposed research is to examine medial temporal lobe (MTL) structure and function in healthy subjects and in older individuals with varying degrees of memory difficulty - from the normal elderly to patients with mild Alzheimer's disease (AD). Four projects are proposed. One project will involve diffusion tensor imaging (DTI) measurements of anisotropy in MTL fiber tracks, which will be evaluated in young, healthy subjects (NC), elderly controls (EC), subjects with mild cognitive impairment (MCI) and patients with mild AD in order to evaluate the structural features that are specific to each group. Three interrelated event-related fMRI projects are proposed that are designed to differentially activate entorhinal, perirhinal and para-hippocampal cortices. Paradigms will be developed in young, healthy subjects and applied to each of the groups of older individuals. The candidate for this Career Development Award has experience in functional imaging of MTL function in young, healthy subjects, but wishes to gain expertise in the use of this and other emerging technologies in magnetic resonance imaging for the evaluation of clinical populations. As part of this proposal, the candidate will receive training in: 1) the clinical design and analysis of ethically sound studies focusing on comparisons between normal elderly, MCI and AD patients, 2) AD neuroanatomy, pathophysiology, neuropsychiatry and potential therapeutic strategies, 3) statistical approaches to the study of clinical populations and time course data sets, and 4) the acquisition and processing of measures of brain anisotropy using DTI.
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