Effects of Aging on Myelinated Nerve Fibers in Monkey Primary Visual Cortex ALAN PETERS, 1,2 * MARK B. MOSS, 1,2 AND CLAIRE SETHARES 1 1 Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts 02118 2 Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia 30322 ABSTRACT In monkeys, myelin sheaths of the axons in the vertical bundles of nerve fibers passing through the deeper layers of primary visual cortex show age-related alterations in their structure. These alterations have been examined by comparing the myelin sheaths in young monkeys, 5–10 years old, with those in old monkeys, between 25 and 33 years of age. The age-related alterations are of four basic types. In some sheaths, there is local splitting of the major dense line to accommodate dense cytoplasm derived from the oligodendrocytes. Other sheaths balloon out, and in these locations, the intraperiod line in that part of the sheath opens up to surround a fluid-filled space. Other alterations are the formation of redundant myelin so that a sheath is too large for the enclosed axon and the formation of double sheaths in which one layer of compact myelin is surrounded by another one. These alterations in myelin increase in frequency with the ages of the monkeys, and there is a significant correlation between the breakdown of the myelin and the impairments in cognition exhibited by individual monkeys. This correlation also holds even when the old monkeys, 25 to 33 years of age, are considered as a group. It is suggested that the correlation between the breakdown of myelin in the old monkeys and their impairments in cognition has not to do specifically with visual function but to the role of myelin in axonal conduction throughout the brain. The breakdown of myelin could impair cognition by leading to a change in the conduction rates along axons, resulting in a loss of synchrony in cortical neuronal circuits. J. Comp. Neurol. 419:364 –376, 2000. © 2000 Wiley-Liss, Inc. Indexing terms: myelin; electron microscopy; cognitive decline; normal aging; senescence To investigate the effects of normal aging on the pri- mate nervous system we have used the rhesus monkey as a model, because when monkeys are subjected to a battery of behavioral tasks, similar to ones that can also be used to evaluate the effects of normal aging on cognition in hu- mans, it is found that they display a similar decline in cognitive function (see Peters et al., 1996). The approach used has been to compare young monkeys with old mon- keys. Consequently, after the monkeys have been behav- iorally tested, their brains are examined microscopically to determine what kinds of morphologic alterations have taken place as a consequence of aging. An assessment is then made about whether any of the morphologic alter- ations correlate with the chronological age, the extent of the observed behavioral decline, or both, in the old mon- keys. In examining the neocortex, our efforts initially were focused on the effects of normal aging on its neurons, but we found no significant loss of neurons from either the visual (Vincent et al., 1989; Peters and Sethares, 1993; Peters et al., 1997), motor (Tigges et al., 1990), or prefron- tal (Peters et al., 1994) cortices with age, and in these same monkeys, Rosene (1993) has encountered no loss of neurons from the hippocampus. Indeed, for both monkeys and humans, there is mounting evidence that there is no significant overall loss of neurons from the cortex during normal aging (Peters et al., 1998a). And, in monkeys, the majority of neocortical neurons show few changes with age beyond an accumulation of lipofuscin within some of them. The exception is layer 1. In area 46 of the prefrontal cortex, at least, layer 1 becomes much thinner with age, Grant sponsor: National Institutes of Health, National Institute on Ag- ing; Grant number: 2PO-AG 00001. *Correspondence to: Alan Peters, Department of Anatomy and Neurobi- ology, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118. Received 27 August 1999; Revised 2 December 1999; Accepted 9 Decem- ber 1999 THE JOURNAL OF COMPARATIVE NEUROLOGY 419:364 –376 (2000) © 2000 WILEY-LISS, INC.