We will perform cognitive and functional assessment of the monkeys in this program project. All 57 monkeys will undergo cognitive assessment with a behavioral test battery that includes tasks of recognition memory (delayed nonmatching to sample, delayed recognition span), spatial memory and executive function (delayed response, reversal learning) that have been found to be sensitive to aging in monkeys as well as in humans. Some of the tests have been developed from, or developed for use with, neuropsychologic evaluation of normal aged human subjects and patients with various forms of age-related dementia. A major goal of this project is to classify the extent of cognitive dysfunction for each monkey based on a composite score derived from the behavioral test battery. This score will then be used to classify aged animals as severely cognitively impaired or as only mildly impaired. This classification will serve as a basis for determining the relationship between cognitive function and the morphological, neurohistochemical, biochemical, molecular and imaging measures obtained by the other projects. We will also evaluate retinal function by assessment of contrast sensitivity in a subset of monkeys with peripheral eye examinations to help determine the functional status of the visual pathways. Contrast sensitivity findings can then be compared with the morphological assessment of the visual pathways. A subset of animals will also undergo activation studies on PET using the visual recognition memory task (DNMS) under two different delay conditions. We will identify the locus and degree of metabolic activity that underlies short-term memory function in the aged monkeys function in the aged monkeys with severe cognitive impairment as compared to that in aged monkeys that are only mildly impaired. Finally, we will evaluate the efficiency of conduction in cortical white matter by measuring electrically evoked potentials across the corpus callosum in a subset of monkeys and comparing this across young, cognitively impaired aged and mildly impaired aged monkeys. In line with one aspect of our overall hypothesis that myelin degeneration may play a significant role in age-related cognitive decline, these observations can then be compared with morphological assessments of the splenium. The assessment and classification of cognitive function in the aged monkey will allow us to evaluate the constellation of neurobiological variables that underlie age-related cognitive dysfunction.
Showing the most recent 10 out of 151 publications
