Agerelated Impairment

The prefrontal cortex is particularly susceptible to the effects of aging at the morphological and molecular level. Although the neurons within the prefrontal cortex of primates are resistant to cell death with aging (O'Donnell et al., 1999; Peters et al., 1994), morphological evidence indicates that these cells may be effectively disconnected from communication due to a loss of synapses, dendritic reduction and a loss of insulating myelin. Decreases in the density of synapses and dendrites in the prefrontal cortex in aged monkeys have been reported, particularly in layer 1. The decrease in synapses in layer 1 may be due to the loss of subcortical cholinergic and dopaminergic projections to the prefrontal cortex (Herzog et al., 2003; Stemmelin et al., 2000; Kaasinen and Rinne, 2002). In addition to a loss in synaptic connections, degeneration of myelin sheaths of nerve fibers also occurs in the pre-frontal cortex of aged monkeys, and this loss significantly correlates with the magnitude of cognitive impairment in the aged group (Peters et al., 2002). Although the prefrontal cortex, particularly the dorsolateral prefrontal cortex in primates, has been most strongly implicated in executive functions, some data indicate that the dorso-medial striatum may also factor in this ability (Ragozzino et al., 2002).

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