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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG014671-04
Application #
6169550
Study Section
Mental Disorders of Aging Review Committee (MDA)
Program Officer
Buckholtz, Neil
Project Start
1997-09-30
Project End
2002-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
4
Fiscal Year
2000
Total Cost
$429,299
Indirect Cost
Name
Columbia University (N.Y.)
Department
Neurology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
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Scarmeas, Nikolaos; Stern, Yaakov (2004) Cognitive reserve: implications for diagnosis and prevention of Alzheimer's disease. Curr Neurol Neurosci Rep 4:374-80
Scarmeas, N; Anderson, K E; Hilton, J et al. (2004) APOE-dependent PET patterns of brain activation in Alzheimer disease. Neurology 63:913-5

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