This is an application for a K23-Mentored Patient-Oriented Research Career Development Award entitled """"""""Structural-functional MRI studies of memory in MCI & AD."""""""" The primary goal of the proposed research is to use an integrated set of structural and functional MRI measures to define the anatomic and physiologic abnormalities underlying memory dysfunction in normal aging, mild cognitive impairment (MCI), and very mild Alzheimer's disease (AD). Quantitative volumetric MRI methods are capable of detecting neuroanatomic abnormalities in aging, MCI and AD some of which are useful as predictors of cognitive decline. Functional MRI (fMRI) tools have begun revealing specific regional brain activity associated with learning and memory. Despite the fact that memory deficits are a hallmark initial symptom of AD, very few fMRi studies have attempted to explore specific abnormalities associated with memory loss in aging, MCI, or AD, and relationships between neurodegenerative structural changes and brain activation patterns are only beginning to be investigated. Therefore, the primary goals of the proposed research are to 1) study regional brain activation patterns associated with encoding of word lists in young and elderly controls, and in patients with MC! and very mild AD, using an event-related """"""""subsequent-memory"""""""" fMRI paradigm, and 2) study the relationships between these activation patterns and regional brain atrophy, measured using quantitative volumetric MRI techniques. The overarching hypotheses of this research are that elderly, MCI, and AD subject groups will show different abnormal fMRI activation patterns during word list learning, and that these abnormalities will not merely reflect atrophy but will indicate attempted compensatory responses, some of which will predict subsequent recall and some of which will not. As part of the proposed research, the candidate seeks training in: 1) fMRI techniques and methods for integrating structural and fMRI data; 2) the cognitive neuroscience of learning and memory and psychometrics of age-related cognitive decline; and 3) ethical clinical research methods. The proposed research plan, didactic courses, and tutorial instruction from mentors and advisors will foster the candidate's development into an independent clinician-scientist using neuroimaging and cognitive methods to study the anatomy and physiology of memory deficits in aging, MCI, and AD.
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