Cognitive deficits occur in normal aging, and can be detected when performance is compared with that of young adult subjects, but age-related deficits are more selective and less severe than those in Alzheimer's disease (AD). The reasons for cognitive decline in aging are not known. The clinical diagnosis of probable AD rests upon the presence of deficits in memory and other cognitive domains, including attention, language, spatial abilities, abstract reasoning, and visual perception. Each patient's pattern of impaired and preserved function is likely to reflect the particular distribution of neuropathological changes in the brain. The goal of the proposed research is to related cognition in normal aging and AD to alterations in the functional magnetic resonance imaging (fMRI) signal within specific cerebral regions. We shall use novel high-speed fMRI methods to (a) obtain clues about the neural substrates of specific cognitive changes in aging and AD to alterations in the functional magnetic resonance imaging (fMRI) signal within specific cerebral regions. We shall use novel high-speed fMRI methods to (a) obtain clues about the neural substrates of specific cognitive changes in aging and AD, (b) document individual differences in those changes, and (c) identify neurophysiological markers that may signal very early AD. In order to achieve these goals, we shall perform 60 fMRI studies per year over a 5- year period in subjects with AD, older control subjects, nd young control subjects. We shall examine correlations between of fMRI signal and behavior in three cognitive domains that are vulnerable to the effects of aging and AD: long-term explicit memory, visual perception, and motor control.
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