Structural changes that occur during normal aging of primate cerebral hemispheres.

Human and non-human primates show cognitive decline during normal aging. Originally, the decline was attributed to a loss of cortical neurons, but recent studies have shown there is no significant cortical neuronal loss with age. Neurons acquire pigment, but the only other obvious changes are in layer 1 of neocortex. Layer 1 becomes thinner as apical tufts of pyramidal cells lose branches, as well as synapses, and at the same time the glial limiting membrane thickens. How dendrites and synapses in deep layers are affected by age is uncertain, but there are decreases in the levels of some neurotransmitters and receptors. Throughout the brain myelin sheaths show signs of breakdown. This may contribute to cognitive decline because it would cause a slowing of conduction along nerve fibers, disrupting the timing in neuronal circuits. Concomitantly, the myelin-forming oligodendrocytes develop swellings along their processes and gain dense inclusions. Microglial cells and astrocytes accumulate large amounts of phagocytosed material with age, although the origins of this material are not known.