Structural alterations and cognitive decline

To date very few parts of the non-human primate brain have been examined to determine the effects of normal aging on the central nervous system in primates that have been behaviorally tested to determine their cognitive status, and hence the possible effects of a given structural change on cognitive decline. As far as gray matter is concerned, studies have been largely confined to area 46 of the prefrontal cortex and to area 17, with a few observations on dentate gyrus, and on the Betz cells in motor cortex. While in contrast, the effects of aging on the fine structure of a number of the well-circumscribed fiber bundles in the cerebral hemispheres have been examined. Detailed accounts of the results of these studies can be found in the reviews by Peters and Kemper (2012) and Morrison and Baxter (2012).

1.     A number of structural factors, such as the total volume of the brain, the numbers of neurons, and astrocytes and microglial cells in various parts of the brain, do not appear to alter significantly with increasing age.

2.     Other structural measures increase with frequency with age, but the frequency does not correlate with cognitive decline. Among these measures are the increase in the frequency of loss of nerve fibers and increased frequency of degenerating myelin sheaths in some fiber tracts; increase in the frequency of senile plaques; increase in frequency of oligodendrocytes; and the loss of synapses from the lower layers of the prefrontal cortex.

3.     Among the structural measures that both increase in frequency with age and correlate with cognitive decline are the increased frequency of degenerating myelin sheaths and loss of nerve fibers in some fiber tracts; the loss of synapses and dendritic spines from the upper layers of area 46 of prefrontal cortex.

What is becoming clear is that cognitive decline during normal aging is not due to a single factor, and that while degenerative alterations are occurring there is also some repair taking place. The most obvious repair is the remyelination that leads to the formation of more numerous and some shorter internodal lengths of myelin that are generated by increasing numbers of oligodendrocytes.

Obviously, more cortical areas need to be examined to determine if such alterations as the synapse losses from the upper layers of area 46 of the cortex, are specific to this cortical area or occur throughout the cortex. And studies need to be carried out to determine the origins of the axon terminals that must degenerate to account for the loss of synapses.


Morrison, J.H. and Baxter, M.G. 2012 The aging cortical synapse: hallmarks and implications for cognitive decline. Brain Ageing. 13: 240 – 250.

Peters, A. and Kemper, T. 2012 A review of the structural alterations in the cerebral hemispheres of the aging rhesus monkey. Neurobiol. Aging. In press.