Table I connects

major findings in cognitive aging to possible neural underpinnings, and Table II summarizes major cognitive neuroscience findings associated with aging and provides potential linkage to the behavioral literature in cognitive aging. Table I Proposed and known connections between cognitive aging phenomena and neural mechanisms. Table II Connections between neural findings and behavioral data in cognitive aging. Behavioral findings Single-mechanism views of decline Speed of processing can account, for nearly all agerelated variance Inhibitors,research,lifescience,medical on cognitive tasks, and so it is important, to understand its neural connection. The neural substrate for age-related slowing, however, is not well specified. There has been some suggestion that slowing is due to a decrease in dopamine receptors (sec a review by Prull et al55), demyelination, and white matter loss (see Raz41 for a review) or to increased dendritic projections that result in circuitous neural processing.74 There is some evidence suggesting that dopamine receptors may play Inhibitors,research,lifescience,medical an important role in accounting for agerelated

Inhibitors,research,lifescience,medical declines in perceptual speed.75,76 Both Backman et al75 and Volkow et al76 reported very substantial correlations between speed and dopamine receptor binding. Virtually no additional variance in speed could be explained when age was added into this relationship, suggesting that dopamine receptor binding is a substantially better predictor of slowing than age. These studies are correlational, and have small numbers of subjects with large age distributions, and so much larger numbers of subjects must be tested to address the reliability of this potentially important causal relationship. Besides the Inhibitors,research,lifescience,medical dopamine receptor studies, there is an additional study that examined the relationship of slowing to activation patterns. Rypma and D’Esposito61 found that, on a working memory task, the fastest old adults showed the most brain activation, whereas the fastest young adults showed the least, brain activity in Inhibitors,research,lifescience,medical the dorsolateral

prefrontal cortex. They speculate that the reasons for this finding could be a shifting of the relationship between neural activation and optimal response discriminability for the old, or that age-related cortical atrophy mediated the high activation Cilengitide for faster older adults and that time on task may have mediated activations for slower young adults. Ultimately, a convincing demonstration of the causes of age-related decline in speed of processing may require a large individual difference study where extreme ends of a distribution of fast, and slow older adults are studied with age tightly controlled (eg, study a single decade from 60 to 69 or 70 to 79 years, so that age is not an additional source of variance), and multiple measures of neural functioning using many techniques (including dopamine D2 receptors) are collected.