Senile dementia of the Alzheimer type (SDAT) is becoming one of the most devasting health problems facing society. In the initial stages of the disease, individuals experience some memory impairment followed later by widespread breakdown in most cognitive functions. In addition, although the deficits are not as severe and progressive, there is also evidence of cognitive breakdowns in healthy aged individuals. The goal of the present proposal is to examine a cognitive mechanism which may underlie the deficits exhibited in both healthy aged and in SDAT individuals, and to begin to develop a formal model which can account for these deficits. The specific target mechanism addressed in this proposal is the ability to inhibit partially activated and competitive information. Recent work from our lab (P01AG03991, Project 3) indicates that healthy aged individuals and to a greater extent SDAT individuals exhibit a breakdown in inhibitory aged individuals and to a greater extent SDAT individuals exhibit a breakdown in inhibitory control across a number of experimental paradigms. In the first series of proposed experiments (Experiments 1-7, Series I), the efficiency of inhibitory processes in healthy aging and SDAT will be examined at a number of distinct levels within the information processing system: perception, memory retrieval, lexical disambiguation, and sentence comprehension. In addition, these experiments will involve manipulations that will allow one to track changes in the time course of inhibitory processes across our subjects groups. The second series of experiments (Experiments 1-4, Series II) will extend to healthy aged and SDAT individuals a set of formal connectionist models that were developed by Cohen and Servan-Schreiber (1992) to account for breakdowns in the efficiency of inhibitory processes in schizophrenic individuals and also to simulate dopaminergic breakdowns in the prefrontal cortex. The proposed experiments will provide an empirical base for formally modelling cognitive changes that occur in healthy aged and SDAT individuals, and also provide a unique opportunity to compare changes in the specific model parameters that are necessary to account for changes in cognitive performance across three distinct populations (schizophrenic, healthy aged, and SDAT individuals). Hence, in collaboration with J. Cohen and D. Servan-Schreiber we intend to use a three-pronged attack utilizing basic cognitive theory, formal connectionist modelling, and neurological evidence to better understand the cognitive changes that are associated with healthy aging and Alzheimer's Disease.
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