Parkinson's disease and healthy aging: independent and interacting effects on action selection.

Functional reorganization of the motor system occurs in response to both aging and Parkinson's disease (PD). Since PD typically develops in older adults, disease progression and the effects of treatment may interact with normal aging. Using event-related functional magnetic resonance imaging, we studied patients "on" and "off" their normal dopaminergic medication, age-matched controls and younger adults on tasks of action and action selection. For manual movements, aging increased activity in bilateral motor, premotor and cingulate cortex. Activation in the premotor regions of "on" patients was higher relative to age-matched controls. However, in contrast to controls and "off" patients, the activations for patients when "on" decreased with age. Voluntary selection of actions was associated with activation in a bilateral network of fronto-parietal cortex. Within this network, advancing severity of PD was associated with decreased activity particularly in premotor and ventrolateral prefrontal cortex. Together, these results reveal very different patterns of age-related changes in health and PD. Younger patients are able to exert greater compensatory activity in premotor cortex than older patients, even after correction for disease severity. This effect is dopamine dependant, and may in part explain the clinical observation of reduced dopamine responsiveness in older patients with PD.