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

David E. Smith, Peter R. Rapp, Heather M. McKay, Jeffrey A Roberts, Mark H. Tuszynski

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4373-4381
Number of pages9
JournalJournal of Neuroscience
Volume24
Issue number18
DOIs
StatePublished - May 5 2004

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Short-Term Memory
Primates
Atrophy
Haplorhini
Neurons
Cholinergic Neurons
Prefrontal Cortex
Brain
Cognitive Dysfunction

Keywords

  • Aging
  • Cell death
  • Cholinergic
  • Cortex
  • Dorsolateral prefrontal cortex
  • Stereology
  • Working memory

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Memory Impairment in Aged Primates Is Associated with Focal Death of Cortical Neurons and Atrophy of Subcortical Neurons. / Smith, David E.; Rapp, Peter R.; McKay, Heather M.; Roberts, Jeffrey A; Tuszynski, Mark H.

In: Journal of Neuroscience, Vol. 24, No. 18, 05.05.2004, p. 4373-4381.

Research output: Contribution to journalArticle

Smith, David E. ; Rapp, Peter R. ; McKay, Heather M. ; Roberts, Jeffrey A ; Tuszynski, Mark H. / Memory Impairment in Aged Primates Is Associated with Focal Death of Cortical Neurons and Atrophy of Subcortical Neurons. In: Journal of Neuroscience. 2004 ; Vol. 24, No. 18. pp. 4373-4381.
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