Patients with Alzheimer's disease (AD) have significant difficulties in their ability to retrieve verbal lexical and semantic knowledge early in the course of the disorder, in addition to the well-described alterations in episodic memory. Delineation of the neural systems that underlie this semantic memory impairment may lead to better understanding of the information processing defect and the identification of those systems that are particularly vulnerable to early neuropathological change in AD. Because the representation and retrieval of semantic knowledge probably involves a distributed network of neocortical areas, it may be the ideal cognitive system for examining the functional manifestations of cortico- cortical disconnection in AD. Using a behavioral task that focuses on semantic memory and and associated information processing during functional Magnetic Resonance Imaging (fMRI) scans, we will compare and contrast the brain regional activation in a longitudinal follow-up study relating fMRI signal change and semantic memory function. Patients with AD (n=40), Mild Cognitive Impairment (n=20), or an Amnesic Syndrome (n=10) will be evaluated as well as age-matched controls (n=20). The patients will be scanned while performing Synonym Judgement, Homonym Judgement, and Visual Control Tasks. Signal change will be correlated with performance on Patterson and Hodges Semantic Memory Battery. This study will permit the evaluation of processes related to semantic memory in AD, and of hypotheses related to understanding the underlying defect responsible for the semantic memory loss. Based on our existing PET data from AD patients, we hypothesize that there will be focal deficit in the function of the inferior temporal lobe. This will, in turn, affect the function of the inferior frontal (related to response selection) and cerebellar cortices (related to response search) as they adapt to the altered functional circuitry in AD.
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