The proposed studies are designed to use Positron Emission Tomographic (PET) neuroimaging to elucidate: 1) relationships between cortical brain subserving normal memory; 2) the functional neuropathology of memory impairment in Alzheimer's disease (AD), particularly in dorsolateral prefrontal cortex; and 3) whether relationships among components involved in the neural circuitry of memory are lost, or altered in a predictable, perhaps compensatory, fashion over time in AD. These goals will be accomplished through 1) a comparison of regional cerebral blood flow (rCBF) activation during tasks designed to selectively activate short and long term memory processing in mildly affected AD patients and demographically matched controls; and 2) a longitudinal design, repeating activation PET studies in the same subjects two years later for comparison. PET imaging of task-related changes in rCBF in normal controls and AD patients will be followed by image subtraction, region-of- interest analysis, and structural equation modeling (path analysis) techniques in order to characterize brain regions that are activated during memory processing. Separate comparisons of baseline and follow-up studies are expected to highlight functional alterations in neural regions that are associated with memory. These studies will test the following hypotheses: 1) In patients with very early AD, activation of dorsolateral prefrontal cortex during performance of memory tasks is prominently reduced in comparison to demographically-matched control participants; 2) The magnitude by which activation of dorsolateral prefrontal cortex is reduced in patients with early AD will be highly correlated with neuropsychological measurements of memory; and 3) Over two years, in a group of patients with mild AD, activation during memory tasks will decline in the dorsolateral prefrontal cortex, but will increase in adjacent regions of frontal cortex. Longitudinal activation studies of control participants will ensure that the observed changes are specific to the disease process. This information is of particular interest because recent models of normal memory functioning emphasize involvement of numerous cortical regions (particularly dorsolateral prefrontal cortex) in memory, in addition to the medial temporal lobe system. The neuropathology of AD is also not restricted to hippocampus and likely involves disruption of a distributed network of cortical regions that participate in memory, possibly through degradation of long cortico- cortical tracts. By characterizing the neural circuitry associated with normal and abnormal memory, these results will provide novel insights into neurobiological substrates of the memory pathology in AD and may furnish strategies for its early diagnosis, assessment and treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
7R29AG013912-05
Application #
6029815
Study Section
Human Development and Aging Subcommittee 3 (HUD)
Project Start
1996-07-01
Project End
2000-01-31
Budget Start
1999-07-01
Budget End
2000-01-31
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Georgia State University
Department
Neurology
Type
Schools of Allied Health Profes
DUNS #
837322494
City
Atlanta
State
GA
Country
United States
Zip Code
30302
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