An examination of cortex of area 46 in the floor of the principal sulcus in the frontal lobe of the rhesus monkey has been carried out using three young (4–6 years of age), one middle-aged (12 years of age), and five old (25–32 years of age) rhesus monkeys. Light microscopic examination revealed no age-related change in the thickness of the cortex, and no changes in the frequency of profiles of neurons displaying nuclei and contained in 250-μm-wide strips of 1-μm-thick sections. Since the diameters of the nuclei of the neurons were found to be the same in the young and old monkeys, it was concluded that there was no change in the numbers of neurons beneath similar areas of cortical surface of area 46 with age. This conclusion was reinforced by an electron microscopic examination, since there was no suggestion of degeneration of the cell bodies of the neurons, which accumulated but little lipofuscin in the old monkeys. However, there were signs of degeneration in some of the dendrites in the upper layers of the cortex in the old monkeys, especially in layer 1, in which many of the dendrites had lost organelles from their cytoplasm. The other notable change was a degeneration of myelinated axons in the deep layers and white matter in some of the old monkeys. In contrast to the neurons, the effects of aging on the neuroglial cells and pericytes were very obvious, since in the old monkeys each type of neuroglial cell accumulated large inclusions within its cytoplasm. Prior to fixation, these monkeys had been behaviorally tested using a series of spatial and visual recognition tasks, which revealed that relative to the young monkeys, the old monkeys as a group displayed memory impairment. On one task, the extent of the impairment for each old monkey correlated well with the extent of degeneration of myelinated fibers in the cortex and white matter. Consequently, it is suggested that age-related cognitive changes are unlikely to be a result of a loss of neurons, but might be due to an alteration in connections between the cortex and other brain structures.

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