Feature article: are neurons lost from the primate cerebral cortex during normal aging?

The concept that cortical neurons are lost with age and that this is the basis for cognitive decline is so embedded in our culture that when someone elderly is a little forgetful it is often said that ‘He/she is losing his/her neurons’. The prime difficulty in determining if neurons are lost from the cerebral hemispheres during normal aging is that it is not possible to count neurons in the brain of the same individual at two different points in time. Consequently, the question of whether neurons are lost with age can only be answered by comparing the brains of older individuals with those of younger individuals, who have been raised in a different environment with a better diet and better health care. What effect this may have on neuronal numbers is not clear. For example, Haug (1985) points out that the increase in height due to secular acceleration, that is from generation to generation, amounts to ~1 mm per year, and data generated by Haug (1985) indicates that as body weight increases, so does brain weight; consequently, ‘brain weight of one generation is proportionally higher than that of the preceding generation as measured in youth’. On the other hand, Pakkenberg and Gundersen (1997) conclude that sex and age are the main determinants of the overall number of neurons in the neocortex, and that body size does not affect neuron number. Such secular trends need to be considered when comparing the brains of young and old humans to determine if there is a neuron loss with age. Yet when comparisons are made in humans, as well as in laboratory animals that have a much shorter life span in a more controlled environment, we conclude that on the basis of the existing data there is no strong evidence to support the concept that significant numbers of neurons are lost from the cerebral cortex during normal aging. Instead, it appears that cortical neurons are largely preserved. The idea that there is a significant loss of neurons during normal aging of the human cortex was put forward by Brody (1955, 1970), who examined the effects of aging of the cortices of subjects between 18 and 95 years of age. He concluded on the basis of cell counts that there is a progressive reduction in neuronal density with age, amounting to 50% in the superior frontal and superior temporal gyri, and between 20 and 30% in the precentral gyrus and visual cortex, although he detected no significant loss of neurons from the inferior temporal gyrus and the postcentral gyrus. This result received a great deal of publicity, and stimulated a number of other studies carried out in the 1970s and 1980s in which similar decreases in neuronal