It is the authors’ guess that behavioral speed represents an aggregate of many different cellular, structural, and functional changes that, occur in the brain with age, and that the particular nature of the changes that have aggregated to result, in slowing could vary considerably from individual to individual. We believe that a focus on a single mechanism to find the underlying cause of age-related decline in speed will be less successful than

a “multiple cause” approach to understanding the indices of neural health with age. The “common cause” view that, sensory Inhibitors,research,lifescience,medical function provides a quick measure of global neural health6 may be even more difficult to isolate. There is evidence that there is a decreased amplitude of the this hemodynamic response in visual cortex with age, although the summation properties of the hemodynamic response do not differ across age.77,78 Inhibitors,research,lifescience,medical On the other hand, the sensory cortex appears to be more resistant to the age-related volumetric decreases compared with other areas of the brain,41 which is hard to reconcile Inhibitors,research,lifescience,medical with the sensory function hypothesis. It, is also difficult to reconcile the simplicity of the behavioral hypothesis with the complexity and distribution of the neuronal correlates of sensory function. In sum, there

is a great need for large studies that examine the neurobiological underpinnings of single-mechanism accounts of cognitive aging. It, is likely that, a multitude of accrued cerebral insults that differ widely among individuals could account, for this relationship. Age-related declines in executive function and long-term Inhibitors,research,lifescience,medical memory Given the volumetric decreases that occur reliably with age in prefrontal cortex, and the finding that shrinkage in this area predicts

poor cognitive performance,41 the linkage between behavioral declines in working memory, inhibition, task-switching, and long-term memory and prefrontal dysfunction is well Inhibitors,research,lifescience,medical established. The rather straightforward picture these becomes more confusing, however, when one examines the relationship of activation patterns in prefrontal cortex to executive function, as there is evidence for increases and decreases in activation in frontal areas with age and evidence for various age-related forms of dedifferentiation, such as contralateral recruitment, unique recruitment, and substitution. Moreover, there is considerable variability Batimastat across studies on specific areas of frontal activation as a function of age. Nevertheless, there can be little doubt that, much of the decline in executive processes observed in older adults is due to frontal dysfunction. Another important, distinction between behavioral and ncuroscience research on aging and memory is that cognitive aging researchers tend to refer to speed of processing and working memory as “cognitive resources” accounting for age-related decline.