This project was formally part of Project 3 in the previous program application and was designed to assess age-related memory dysfunction in the monkey as a reflection of degenerative changes in the temporal lobe limbic system. Additional areas of cognitive function were also assessed to provide information on the effects of age on a wide range of behavior such as visuospatial function and attention. Because of changes in the focus of the program, the behavioral and anatomical studies were expanded and, as a result, this project now centers exclusively on the behavioral changes that accompany aging in the monkey. It will be focused primarily on the cognitive domains of cognitive flexibility (""""""""executive function"""""""") and memory. These two areas ar known to undergo significant decline in normal human aging and to a greater extent in several types of dementia. The anatomical loci that underlie these functions are believed to be the prefrontal association cortex and the temporal lobe limbic system, respectively. Our overall hypothesis, that impairments in these functions result from synaptic dysfunction or disconnection rather than overt cell loss, will be tested by correlating age-dependent cognitive decline in the two identified behavioral domains with the anatomical, neurochemical and metabolic measures that will be obtained from the dorsolateral prefrontal cortex and the temporal lobe limbic system in the same monkeys. Accordingly, in this project, all monkeys (except five """"""""pilot"""""""" animals) will undergo a battery of behavioral tests designed to assess cognitive flexibility and memory function as well as other cognitive areas. In our attempt to parallel closely our studies in aged monkeys to those in aged humans, many of the tasks to be used are derived from those administered clinically to geriatric patients. Similarly, one of the tests in monkeys developed in our laboratory is now used widely as a early measure of early memory dysfunction in aged adults with suspected dementia. In another phase of this project, we will assess cognitive function longitudinally in a group of five young (5-9 yrs) monkeys and compare their course to a group of five middle aged (15-19 yrs) monkeys. These data might be of particular value to establish empirical support for hypotheses and inference derived from the cross sectional data.
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