The goal of this project is to use functional magnetic resonance imaging (fMRI) to evaluate the relationship between age-associated changes in medial temporal lobe (MTL) function, and other brain regions, and age- associated changes in declarative or explicit memory. MTL neuropathology is closely related to severe declarative memory failure in Alzheimer's disease (AD), but there is growing evidence that milder memory impairment in older individuals is also associated with MTL dysfunction, and that this impairment may signal a preclinical stage for AD in at least some of these individuals. We propose to examine two fundamental stages of declarative memory (encoding and retrieval) in five groups of younger (ages 20-35) and older (Ages 65-79) subjects: (1) young healthy controls ages 20-35 (YNC); (2) older healthy controls who do not have cognitive impairment (ONC); (3) older subjects who have mild cognitive impairment on declarative memory tests (MCI-memory); (4) older subjects who have mild cognitive impairment on tests other than memory (MCI-other); and (5) older subjects with early-stage AD. With these groups, we can examine cross- sectionally how brain activation related to declarative memory varies in successful aging, in mild cognitive impairment that is specific to memory, and in A.D. Primary emphasis will be neural activation that occurs during encoding and retrieval in the structures that comprise the medial temporal lobe (entorhinal cortex, hippocampus, parahippocampal gyrus). Secondary emphasis will be neural activation that occurs during encoding and retrieval in other neocortical areas (particularly frontal regions). Additional data will include high-resolution structural MRI and Diffusion Tensor Imaging to quantify macro and microstructural volume and integrity of the brain. This additional information may provide important information in the interaction of fMRI signal and changes in global and regional volume and integrity in healthy and pathological aging.

National Institute of Health (NIH)
National Institute on Aging (NIA)
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Rush University Medical Center
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