Deterioration of general knowledge of language, concepts, and facts (i.e., semantic memory) is one of the most devastating and least understood aspects of the dementia associated with Alzheimer's disease (AD). This project will examine the effect of AD progression on the integrity of semantic memory and will evaluate the possible that measures of semantic memory can effectively track and predict global cognitive decline in D patients. In addition, the relationship between the integrity of semantic memory and measures of atrophy of temporal lobe association cortices that are thought to mediate this form of memory will be explored. Sixty mildly demented AD patients and 60 age- and education-matched normal control (NC) subjects will be assessed at an initial test session and at each of three subsequent annual sessions with a battery of tests that includes sensitive measures of semantic categorization, naming, sorting, fluency, and semantic priming. Data derived from these measures will be subjected to multi- dimensional graphic analysis techniques that model the semantic network fro particular categories of knowledge, and to dynamic analyses of the time course of retrieval from semantic memory that can differentiate between the loss of exemplars and retrieval slowing. Quantitative measures of lateral and inferior temporal lobe cortical atrophy revealed by MRI will be used to explore the relationship between semantic memory dysfunction and brain pathology. The proposed studies may increase our ability to detect and tract the progression of AD over time and lead to a greater understanding of the neural systems in which various aspects of semantic information are stored and distributed.
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