COGNITIVE FUNCTION IN AGED MONKEY

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Significance The overall goals of this project are to establish a non-human primate model for defining the neurobiological basis of age-related cognitive decline. Objectives Large samples of young (n = 20) and aged (n = 40) rhesus monkeys will be tested across procedures specifically designed to examine these mnemonic processing capacities 1) a nonhuman primate analog of paired associate learning, 2) a transitive inference procedure measuring learning and memory for hierarchical relationships, and 3) a maze navigation task emphasizing learning and memory for complex spatial relationships. In order to document the selectivity and sensitivity of these assessments, performance will also be evaluated on several standard learning and memory procedures. Results These studies are providing the first systematic analysis of declarative memory function in the aged nonhuman primate, establishing an appropriate framework of evidence for relating our behavioral observations to selected hormonal and neurobiological signatures of aging. Urinary estrogen levels have been associated with impaired performance on delayed response tastes. Future Directions Experiments will be initiated to test the potential protective effects of hormone replacement on age-related learning and memory impairment. Studies combining immunohistochemistry and quantitative confocal laser microscopy are also proposed to determine whether declarative memory impairment is linked to the substantial loss of NMDA receptors recently documented in the aged monkey hippocampus. These studies will test the hypothesis that estrogen deficiency influences cognitive aging through effects on hippocampal glutamate receptors that mediate learning-related cellular plasticity. The proposed research is expected to substantially advance progress toward defining the interactions between cognitive, endocrine and neurobiological aging in primates. KEY WORDS memory, aging, learning, estrogen deficiency FUNDING NIH Grant AG10606 PUBLICATIONS Rapp, P.R. (1998) Representational organization in the aged hippocampus. Hippocampus, 8, 432-435. Rapp, P.R. (1998) Quantitative morphometry in the study of normal cognitive aging. In Quantitative Neuroanatomy A Picture is Worth a Thousand Words, but a Number is Worth a Thousand Pictures. J. Morrison and P. Hof (eds.), Washington, D.C. Society for Neuroscience, pp. 56-65.