The long-term objective of this project is to understand the changes in brain and cognitive function that take place before the onset of the clinical symptoms of Alzheimer's disease. Mild cognitive impairment (MCI) is a diagnostic term describing elderly individuals with an isolated episodic memory deficit that is often a transition state between normal aging and Alzheimer's disease (AD). Thus, the study of MCI offers insight into the changes in brain and cognitive function that occur before the widespread cognitive deficits of Alzheimer's disease are present. Neuropathological studies suggest that the degree of neuropathology in the neo-cortex is likely to be a critical difference between MCI and AD. The proposed experiments will evaluate neo-cortical function in MCI using psychological and neurophysiological methods by (1) assessing basic cognitive processes thought to reflect neo-cortical function, and (2) measuring cortical potentials directly, using non-invasive event-related potentials. ? ? The Specific Aims are: (1) to test the hypothesis that elementary cognitive functions (processing speed, attention) are impaired in MCI, (2) to test the hypothesis that cortical interactions between prefrontal cortex and sensory cortices are compromised in MCI, and (3) to determine if brain activity and behavioral measures can predict subsequent conversion to AD in individual MCI subjects, using a longitudinal study design. ? ? The proposed experiments are important because they will advance our understanding of the brain and cognitive changes that accompany the development of Alzheimer's disease. Experimental findings may also have clinical applications for determining the risk of conversion from MCI to Alzheimer's disease in individual MCI patients, and could provide objective measures of treatment efficacy.
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