The goal of the proposed research is to improve our understanding of memory and language dysfunctions in the early stages of Alzheimer's disease (AD) by assessing the learning capacities of knowledge systems that subserve perception, language, and memory. Our recent studies suggest that learning mechanisms supporting early stages of object and word visual recognition in which a percept is transformed into a structural representation may be intact in patients with early AD. Four experiments test the integrity of perceptual-structural learning capacities in early AD for verbal and for nonverbal materials and also explore the mechanism of this sort of visual learning. A second set of experiments examines the relation between intact and impaired forms of lexical-semantic knowledge in AD and the relation of those forms of knowledge to learning that may support word retrieval. These experiments are motivated by new findings from our laboratory about lexical-semantic learning in early AD. A third experiment examines the possibility of item-specific semantic knowledge deficits in early AD and how such deficits affect specific language and memory functions. These issues are examined in 7 multi-experiment studies with at least 24 mildly- to-moderately demented AD patients and 24 normal control subjects in each study. The newly obtained evidence will guide the development of a preliminary hypothesis relating the typical sequence of neuropathological compromise in early AD to the pattern of preserved and impaired learning capacities demonstrated by these patients. Part of the hypothesis will be tested directly by relating reductions of hippocampal tissue, as calculated from MRI scans, to multiple measures of memory. The elaboration of a model of the specific pattern of behavioral compromise in the early stages of typical AD that is supported by empirical evidence and integrated with neuroanatomical evidence should be useful in the development of valid and sensitive behavioral testing instruments for assessing the efficacy of putative cognition-enhancing drugs in AD and other age-related neurological diseases.
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