Gender	Male
E-mail	peter.rapp@mssm.edu
Education and Training	Ph.D., University of North Carolina

Education and Training	Ph.D., University of North Carolina

Cognitive and Neurobiological Consequences of Aging
Research on the neurology of learning and memory has progressed at a remarkable pace over the last twenty years, and our laboratory has capitalized on this body of evidence to address several inter-related topics. One line of research is aimed at establishing a detailed neuropsychological account of cognitive aging in the monkey. These studies take advantage of both established and newly developed behavioral testing procedures designed to provide a window on the functional status of brain regions implicated in learning and memory. Our accumulated evidence indicates that memory processes dependent on the prefrontal cortex are particularly susceptible to aging, while the status of memory mediated by the hippocampus and closely related medial temporal lobe structures varies dramatically across individuals. Variability in the cognitive effects of aging has attracted considerable attention in recent years, partly because it provides a valuable framework for identifying the neurobiological alterations that are most tightly coupled to age-related behavioral decline. In recent studies of this sort we have demonstrated that hippocampal neuron loss is a less prominent feature of normal aging than previously presumed, and that cell death in the aged hippocampus fails to account for the learning and memory impairment observed in a substantial proportion of older individuals. Other biomarkers, however, are significantly correlated with cognitive decline, including hormonal changes and metabolic activity in the aged hippocampus. These findings count against the long-standing concept that frank neuronal degeneration is the proximal cause of behavioral aging, and instead suggest that cognitive impairment results from functional changes within the surviving architecture of the brain. Receptor systems responsible for learning-related cellular plasticity may play and important role in this regard, and this proposal is currently under investigation in collaboration with other members of the Neurobiology of Aging Laboratories.

A closely related line of inquiry in the laboratory is intended to better define the specific nature of memory supported by the individual structures comprising the hippocampal system. A central aspect of this project involves the development of new behavioral assessment procedures for the monkey, emphasizing precisely those aspects of memory that are thought to critically depend on intact hippocampal function. Utilizing these new tasks, studies in young monkeys have begun to examine the effects of selective damage to the hippocampus and associated cortical areas in the medial temporal lobe. Ultimately, the same procedures should provide valuable tools for establishing a more complete neuropsychological account of cognitive aging in the monkey, and for the rational development of therapeutic strategies for treating cognitive disorders of aging.

Rapp P, Gallagher M. Preserved neuron number in the hippocampus of aged rats with spatial learning deficits. Proc Natl Acad Sci U S A 1996 Sep 3; 93(18): 9926-30.

Eberling JL, Roberts J, Rapp P, Tuszynski MH, Jagust WJ. Cerebral glucose metabolism and memory in aged rhesus macaques. Neurobiol Aging 1997 Jul-Aug; 18(4): 437-43.

Rapp P, Kansky MT, Roberts J. Impaired spatial information processing in aged monkeys with preserved recognition memory. Neuroreport 1997 May 27; 8(8): 1923-8.

Roberts J, Gilardi KV, Lasley B, Rapp P. Reproductive senescence predicts cognitive decline in aged female monkeys. Neuroreport 1997 May 27; 8(8): 2047-51.

Smith TD, Adams MM, Gallagher M, Morrison J, Rapp P. Circuit-specific alterations in hippocampal synaptophysin immunoreactivity predict spatial learning impairment in aged rats. J Neurosci 2000 Sep 1; 20(17): 6587-93.