The proposed studies are designed to contrast the processes of reserve and compensation in normal aging and probable Alzheimer's disease (AD). Imaging and epidemiologic evidence strongly suggest that AD patients actively compensate for AD pathology. Previous studies have suggested that this takes the form of more marked and extensive recruitment of brain areas, perhaps reflecting the utilization of alternate or additional cognitive processes. Imaging studies in heathy controls suggest that as a task is made more difficult there is also evidence of increased task-related activation. We hypothesize that these findings in AD and controls represent the same process, which we call reserve: a normal response to increasing task difficulty. In contrast, compensation is an abnormal attempt to maintain response in the face of disease pathology. The first study goal is to identify and contrast patterns of functional activity associated with reserve and compensation during memory task performance. To address this issue, we propose to systemically manipulate and equate task difficulty across patients and controls. This will allow us to differentiate between compensation and reserve . The second goal is to identify patterns of functional activity related to individual variations in performance. We hypothesize that individual variation in reserve may underlie our and others' observation that patients with comparable levels of AD pathology can vary widely in measured clinical severity and test performance. The third goal is to determine whether the patterns of functional activation underlying reserve and compensation are similar or different when the cognitive demands of the task differ. We hypothesize aspects of reserve remain comparable across different tasks. While we will study reserve and compensation in response to ad pathology, these issues have relevance for understanding the brain's response to any pathology. In addition, the methodologic issues we raise are applicable to all functional imaging studies of cognitive task performance in patient populations.
Showing the most recent 10 out of 17 publications
