Deposition of amyloid-beta (Abeta) protein in the brain has been postulated to be the cause of Alzheimer's disease (AD). However, the finding of post-mortem amyloid plaque deposition in the brains of individuals in whom the absence of clinical AD was well-documented prior to their death has been variably interpreted to both support and refute this hypothesis. This wide range of interpretations is partly due to the lack of in vivo longitudinal data on the natural history of amyloid deposition in persons who do not show clinical symptoms of dementia. This proposal will assess in vivo evidence of brain amyloid deposition in """"""""normal"""""""" elderly subjects who do not meet clinical criteria for mild cognitive impairment (MCI) or AD. We refer to these subjects as """"""""clinically unimpaired"""""""". We will address three fundamental questions: 1) How common is amyloid deposition in clinically unimpaired elderly; 2) Is the greater variability of cognitive performance in the clinically unimpaired elderly (compared to the young) explained by the presence or absence of amyloid deposition and 3) Will clinically unimpaired elderly who have evidence of amyloid deposition invariably progress to a clinical diagnosis of MCI or AD? Our group has developed an in vivo amyloid imaging positron emission tomography (PET) radiotracer termed """"""""Pittsburgh Compound-B"""""""" (PIB). We propose to use this new amyloid imaging technology to provide insight into the questions raised above. The proposed research will test the central hypotheses that amyloid deposition can be demonstrated in clinically unimpaired elderly, that amyloid deposition will correlate with common cognitive changes of """"""""normal aging"""""""" and both amyloid deposition and sub-clinical cognitive deficits will progress in tandem over time. With extended periods of observation that will begin in, but extend beyond this study, we hypothesize that this progression will lead to clinical AD. Subjects in their 60's, 70's and 80's will be screened to rule-out dementia using a standard """"""""diagnostic neuropsychological assessment"""""""". Clinically unimpaired subjects will be further tested, using well-established cognitive measures, to determine the presence of sub-clinical decrements in cognitive performance commonly found in """"""""normal aging"""""""". All subjects will receive PET imaging with PIB and FDG (the latter being the current standard for functional neuroimaging in AD). All assessments will be performed at baseline and 24 months. We will complete 24 month follow-up on 15 65-69 y/o, 25 75-79 y/o and 25 80-84 y/o subjects. Subjects identified as amyloid-positive at 24 months will be followed yearly in years four and five.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AG025516-03
Application #
7217341
Study Section
Clinical Neuroscience and Disease Study Section (CND)
Program Officer
Wagster, Molly V
Project Start
2005-03-01
Project End
2010-02-28
Budget Start
2007-04-15
Budget End
2008-02-29
Support Year
3
Fiscal Year
2007
Total Cost
$459,409
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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