Changes in cortical circuits during aging

John Morrison, Patrick R. Hof

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


In this paper, we review the key pathologic events in human hippocampus and neocortex that underlie Alzheimer's disease, and contrast these events with those of normal aging in these same brain regions of animal models. Alzheimer's disease is characterized by senile plaque and neurofibrillary tangle formation, and more importantly, extensive yet selective neuron death and synapse loss in the hippocampus and neocortex. Particular subsets of pyramidal cells and their projections, such as the connection between entorhinal cortex and hippocampus and corticocortical interconnections in neocortex, are particularly vulnerable. The extensive degeneration of these circuits leads directly to dementia. Normal aging can be accompanied by a more modest disruption of memory, yet neuron death is unlikely to be a significant contributor to age-associated memory impairment. While the death of neurons is minimal in normal aging, the same hippocampal and neocortical circuits that die in Alzheimer's disease are vulnerable to sublethal age-related shifts in morphology, neurochemical phenotype and synaptic alterations that might impair function. The response of these circuits to circulating estrogen levels is also discussed, since the critical interactions between reproductive senescence and brain aging may affect excitatory synaptic transmission in the hippocampus as well. Thus, subtle changes in the aging spine and synapse may be the key to age-related memory decline, whereas degeneration of entire circuits is the more prominent substrate for functional decline in Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)294-304
Number of pages11
JournalClinical Neuroscience Research
Issue number5-6
StatePublished - Jan 1 2003
Externally publishedYes


  • Alzheimer's disease
  • Estrogen replacement
  • Hippocampus
  • Mild cognitive impairment
  • Neocortex
  • NMDA receptor

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry


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