The first proof-of-concept studies using the new positron emission tomography (PET) tracer, Pittsburgh compound-B (PIB), showed that PIB-PET imaging detected amyloid deposition in the brains of living AD subjects in a pattern similar to that predicted by autopsy studies. The overall objective of this proposal is to define amyloid deposition in early phases of AD and aid in the characterization of PIB as a surrogate marker of amyloid deposition by examining PIB retention and other metabolic and structural makers. The studies ask 3 major questions: 1) in normal elderly subjects, subjects with mild cognitive impairment (MCI), and mild, moderate, and severe Alzheimer's disease (AD), will deposition of PIB be detectable and correlate quantitatively with the level of severity of overall cognition, or cognitive functions referable to specific areas of the brain? 2) Will these subjects show increases in PIB retention (amount of beta amyloid) in a longitudinal study in which PIB-PET and cognitive assessments are performed annually for up to three years? 3) What is the prevalence of PIB retention across the clinical spectrum of Parkinson's Disease (PD), PD with dementia (PDD) and Dementia with Lewy Bodies (DLB); how much amyloid deposition underlies clinical dementia symptoms observed in these patients? We will also perform fluorodeoxyglucose PET (FDG-PET) and MRI to correlate metabolic and volumetric data, cognition, and PIB deposition. To accomplish these objectives we have established an Administrative Core to oversee & coordinate the projects, budgets, and data transfers; a Clinical Core to identify and assess subjects from the University of Pittsburgh ADRC and the Movement Disorders Clinics in the Department of Neurology and the Pittsburgh VA Health System and an Imaging, Methodology and Statistics (IMS) Core comprised of researchers from the UPMC PET Center and the Department of Radiology. Effective collaborations are assured by the fact that the investigators have worked together closely in research & care in the ADRC and the Parkinson's Center for many years. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
3P01AG025204-04S1
Application #
7613745
Study Section
Special Emphasis Panel (ZAG1-ZIJ-4 (O6))
Program Officer
Buckholtz, Neil
Project Start
2005-05-15
Project End
2010-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
4
Fiscal Year
2008
Total Cost
$142,645
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Hu, Ziheng; Wang, Lirong; Ma, Shifan et al. (2018) Synergism of antihypertensives and cholinesterase inhibitors in Alzheimer's disease. Alzheimers Dement (N Y) 4:542-555
Zhao, Yujing; Tudorascu, Dana L; Lopez, Oscar L et al. (2018) Amyloid ? Deposition and Suspected Non-Alzheimer Pathophysiology and Cognitive Decline Patterns for 12 Years in Oldest Old Participants Without Dementia. JAMA Neurol 75:88-96
Jansen, Willemijn J; Ossenkoppele, Rik; Tijms, Betty M et al. (2018) Association of Cerebral Amyloid-? Aggregation With Cognitive Functioning in Persons Without Dementia. JAMA Psychiatry 75:84-95
Wilckens, Kristine A; Tudorascu, Dana L; Snitz, Beth E et al. (2018) Sleep moderates the relationship between amyloid beta and memory recall. Neurobiol Aging 71:142-148
Minhas, Davneet S; Price, Julie C; Laymon, Charles M et al. (2018) Impact of partial volume correction on the regional correspondence between in vivo [C-11]PiB PET and postmortem measures of A? load. Neuroimage Clin 19:182-189
Yan, Qi; Nho, Kwangsik; Del-Aguila, Jorge L et al. (2018) Genome-wide association study of brain amyloid deposition as measured by Pittsburgh Compound-B (PiB)-PET imaging. Mol Psychiatry :
La Joie, Renaud; Ayakta, Nagehan; Seeley, William W et al. (2018) Multisite study of the relationships between antemortem [11C]PIB-PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology. Alzheimers Dement :
Cohen, Ann D; McDade, Eric; Christian, Brad et al. (2018) Early striatal amyloid deposition distinguishes Down syndrome and autosomal dominant Alzheimer's disease from late-onset amyloid deposition. Alzheimers Dement 14:743-750
Marquié, Marta; Normandin, Marc D; Meltzer, Avery C et al. (2017) Pathological correlations of [F-18]-AV-1451 imaging in non-alzheimer tauopathies. Ann Neurol 81:117-128
Mi, Zhiping; Abrahamson, Eric E; Ryu, Angela Y et al. (2017) Loss of precuneus dendritic spines immunopositive for spinophilin is related to cognitive impairment in early Alzheimer's disease. Neurobiol Aging 55:159-166

Showing the most recent 10 out of 106 publications