The declining infrastructure of the aging brain.

Great effort has been dedicated to mapping the functional architecture of the brain in health and disease. The neural centers that support cognition and behavior are the "hubs" defining the salient geographic landmarks of the cerebral topography. Similar to urban cartography, however, the functionality of these hubs is critically dependent on the infrastructure permitting the transfer of relevant information from site to site, and this infrastructure is susceptible to deterioration. The groundwork of the brain lies in the form of the complexly organized myelinated nerve fibers responsible for the inter-regional transmission of electrical impulses among distinct neural areas. Damage to the myelin sheath and reduction in the total number of nerve fibers with aging are thought to result in a degradation in the efficiency of communication among neural regions and to contribute to the decline of function in older adults. This article describes selected studies that are relevant to understanding the deterioration in structural connectivity of the aging brain with a focus on potential consequences to functional network activity. First, the neural substrates of connectivity and techniques used in the study of connectivity are described with a focus on neuroimaging methodologies. This is followed with discussion of the negative effects of age on connective integrity, and the possible mechanisms and neural and cognitive consequences of this progressive disconnection. Given the potential for natural repair of certain elements of the connective network, understanding the basis of age-associated decline in connectivity could have important implications with regard to the amelioration of neural dysfunction and the restoration of the infrastructure necessary for optimal function in older adults.