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The Journal of Neuroscience, May 5, 2004, 24(18):4373-4381; doi:10.1523/JNEUROSCI.4289-03.2004

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Behavioral/Systems/Cognitive
Memory Impairment in Aged Primates Is Associated with Focal Death of Cortical Neurons and Atrophy of Subcortical Neurons

David E. Smith,¹ Peter R. Rapp,² Heather M. McKay,³ Jeffrey A. Roberts,³ and Mark H. Tuszynski^1,4

¹Department of Neurosciences, University of California, San Diego, La Jolla, California 92093-0626, ²Kastor Neurobiology of Aging Laboratories, Fishberg Research Center for Neurobiology, New York, New York 10029, ³California National Primate Center, Davis, California 95616, and ⁴Veterans Administration Medical Center, San Diego, California 92161

Mechanisms of cognitive decline with aging remain primarily unknown. We determined whether localized cell loss occurred in brain regions associated with age-related cognitive decline in primates. On a task requiring the prefrontal cortex, aged monkeys were impaired in maintaining representations in working memory. Stereological quantification in area 8A, a prefrontal region associated with working memory, demonstrated a significant 32 ± 11% reduction in the number of Nissl-stained neurons compared with young monkeys. Furthermore, the number of immunolabeled cholinergic neurons projecting to this region of cortex from the nucleus basalis was also reduced by 50 ± 6%. In contrast, neuronal number was strikingly preserved in an adjoining prefrontal cortical region also associated with working memory, area 46, and in the component of the nucleus basalis projecting to this region. These findings demonstrate extensive but highly localized loss of neocortical neurons in aged, cognitively impaired monkeys that likely contributes to cognitive decline. Cell degeneration, when present, extends transneuronally.

Key words: aging; cell death; working memory; dorsolateral prefrontal cortex; stereology; cortex; cholinergic

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Received Sep 20, 2003; revised February 23, 2004; accepted February 27, 2004.

This article has been cited by other articles:

				G. E. Alexander, K. Chen, M. Aschenbrenner, T. L. Merkley, L. E. Santerre-Lemmon, J. L. Shamy, W. E. Skaggs, M. H. Buonocore, P. R. Rapp, and C. A. Barnes Age-Related Regional Network of Magnetic Resonance Imaging Gray Matter in the Rhesus Macaque J. Neurosci., March 12, 2008; 28(11): 2710 - 2718. [Abstract] [Full Text] [PDF]

				L. Cruz, D. L. Roe, B. Urbanc, H. Cabral, H. E. Stanley, and D. L. Rosene Age-related reduction in microcolumnar structure in area 46 of the rhesus monkey correlates with behavioral decline PNAS, November 9, 2004; 101(45): 15846 - 15851. [Abstract] [Full Text] [PDF]

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