The goals of this project are: 1) to characterize the functional networks of healthy aged brains while engaged in sensory, declarative memory and working memory tasks and to contrast these physiological patterns with age-matched patients diagnosed as having mild Alzheimer's Disease (AD) or minimal cognitive impairment (MCI); 2) to follow longitudinally patients diagnosed as AD or MCI and the healthy elderly, via repeat testing across a 5-year period in order to document functional changes in patients where the memory deficits are likely to become progressively worse. A long-term goal is to use these results to develop new protocols that will enable us to diagnose AD earlier than current capabilities permit (i.e., preclinically) and to develop a better understanding of the neural mechanisms mediating AD so that appropriate intervention strategies can be developed. Neuropathology studies reveal deficits in the medial temporal lobes (i.e., presence of senile plaques and neurofibrillary tangles) of mild AD patients. In contrast, recent studies in the elderly (nonhuman primates and humans) suggest alterations in the microstructure of neurons or glial cells (e.g., alterations in myelin sheaths) accompany normal aging that have a more generalized effect, often referred to as sensory and cognitive slowing. We hypothesize that mild AD patients will show impairment on a delayed verbal recognition memory task, a task that normally evokes activity in medial temporal lobe structures, as well as orbitofrontal regions. If normal aging results from a slow degenerative process, then effects should be evident across sensory and cognitive tasks. As AD progresses, there will be more overlap in the affected cortical structures. A functional brain imaging technique, magnetoencephalography (MEG), that has good spatial and temporal resolution, will be used in conjunction with anatomical magnetic resonance imaging (MRI) to characterize the functional networks associated with various sensory and cognitive tasks. Automated source localization and cross-covariance procedures will be used for identifying the active cortical networks affected by MCI and AD. Ten mild AD/MCI patients will be tested the first year and compared with 20 healthy age-matched controls. All 30 patients/subjects will have repeat exams (MEG, MRI, neuropsychological exams, etc) for each of the remaining 4 years. We anticipate some subject mortality in the healthy elderly group which will allow us to add more patients to the MCI and mild AD group across time. This longitudinal information will help elucidate the neural mechanisms affected by MCI and AD. ? ?
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