Neurobiological bases of age-related cognitive decline in the rhesus monkey

A. Peters, D. L. Rosene, M. B. Moss, T. L. Kemper, C. R. Abraham, J. Tigges, M. S. Albert

Research output: Contribution to journalReview article

Abstract

The rhesus monkey offers a useful model of normal human aging because when monkeys are tested on a battery of behavioral tasks that can also be used to evaluate cognition in humans, it is found that the monkeys undergo an age related decline in several domains of cognitive function as do humans. In monkeys these changes begin at about 20 years of age. To determine what gives rise to this cognitive decline, we have examined several parameters in the brains of monkeys. Some parameters do not change with age. Examples of this are the numbers of neurons in the neocortex and hippocampal formation, and the numbers of synapses in the hippocampal formation. Changes in other parameters can be positively correlated with chronological age; examples of this are numbers of neuritic plaques, a decrease in the numbers of neurons in the striatally projecting pars compacta of the substantia nigra, and a decrease in the thickness of layer 1 in primary visual cortex. But the most interesting changes are those that correlate either with cognitive decline alone, or with both cognitive decline and chronological age. Among these are a breakdown in the integrity of myelin around axons, an overall reduction in the volume of white matter in the cerebral hemispheres, thinning of layer 1 in area 46 of prefrontal cortex, and decreases in the cell density in cortically projecting brain stem nuclei. To date then, our studies suggest that the cognitive declines evident in the rhesus monkey may be a consequence of changes in layer 1 and in the integrity of myelinated axons, rather than an age related loss of cortical neurons or synapses, as has long been assumed.

Original languageEnglish (US)
Pages (from-to)861-874
Number of pages14
JournalJournal of neuropathology and experimental neurology
Volume55
Issue number8
DOIs
StatePublished - Aug 1996
Externally publishedYes

Keywords

  • Aging
  • Behavior
  • Cerebral cortex
  • Hippocampal formation
  • Macaca mulatta
  • Mylein
  • Neuronal loss

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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