A major emphasis of the Wisconsin ADRC is identifying features and avenues for early intervention in the preclinical state of AD. Project 1 of the Wisconsin ADRC is about early characterization of AD using a fibrillar amyloid positron emission tomography imaging method with Pittsburgh Compound B [C11]PiB. We seek to determine the relationship between amyloid binding measured with PiB,and neural activity where neural activity is indexed by a) cognitive function/decline, b) BOLD activity during a memory task, and c) resting cerebral blood flow (CBF) imaging in a cohort of cognitive decliners at high risk for AD. The overall hypothesis is that fibrillar amyloid binding to [C11JPIB will be related to markers of neural function in cognitive decliners at high risk for AD. We will focus on the posterior cingulate/precuneus brain region (which is known to have high amyloid burden in AD) and probe this region with 1) a functional MRI task previously shown to activate the region, 2) resting cerebral blood flow (CBF) using a whole-brain pseudo- continuous arterial spin labeling technique (ASLCBF),and [C11]PIB imaging.
Specific Aim 1 : To determine whether PIB binding in the posterior cingulate is associated with cognitive decline to MCI in a cohort of subjects who we have followed over a 4-year interval. Furthermore we will determine whether PIB binding in the posterior cingulate predicts subsequent decline.
Specific Aim 2 : To determine whether PIB binding in the posterior cingulate is associated with imaging markers of neural function (BOLD fMRI during a memory task, and resting cerebral blood flow).
Specific Aim 3 : To determine if the relationship between PIB binding in the posterior cingulate is related to cerebral spinal fluid levels of amyloid-beta42 andtau. To accomplish these aims we will identify 30 subjects who have declined over the prior four years to MCI and match them to 30 cognitively-stable subjects over the same interval. All will participate in a single study visit to include PiB,fMRI, ASL CBF, and a lumbar puncture for CSF collection. All will be subsequently followed annually by the Clinical Core of the Wisconsin ADRC to determine their cognitive status including decline to AD. The data collected in this project will be analyzed to determine the relationship of PiB with prior and subsequent cognitive decline and imaging markers of neural function using voxel-wise statistics.

Public Health Relevance

(Seeinstructions): By the time a patient exhibits symptomatic dementia, devastating neural loss has already occurred. New methods for characterizing brain dysfunction are needed to facilitate early detection and early intervention. By applying advanced imaging to a well-characterized high-risk longitudinally-followed cohort, we are in a unique position to provide a greater understanding of early brain changes that occur in prodromal AD.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
5P50AG033514-05
Application #
8449652
Study Section
Special Emphasis Panel (ZAG1-ZIJ-4)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
5
Fiscal Year
2013
Total Cost
$51,221
Indirect Cost
$16,762
Name
University of Wisconsin Madison
Department
Type
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Willette, Auriel A; Johnson, Sterling C; Birdsill, Alex C et al. (2015) Insulin resistance predicts brain amyloid deposition in late middle-aged adults. Alzheimers Dement 11:504-510.e1
Joshi, Gururaj; Gan, Kok Ann; Johnson, Delinda A et al. (2015) Increased Alzheimer's disease-like pathology in the APP/ PS1?E9 mouse model lacking Nrf2 through modulation of autophagy. Neurobiol Aging 36:664-79
Engelman, Corinne D; Koscik, Rebecca L; Jonaitis, Erin M et al. (2014) Investigation of triggering receptor expressed on myeloid cells 2 variant in the Wisconsin Registry for Alzheimer's Prevention. Neurobiol Aging 35:1252-4
Kim, Hyunwoo J; Adluru, Nagesh; Bendlin, Barbara B et al. (2014) Canonical Correlation Analysis on Riemannian Manifolds and Its Applications. Comput Vis ECCV 8690:251-267
Hoy, Andrew R; Koay, Cheng Guan; Kecskemeti, Steven R et al. (2014) Optimization of a free water elimination two-compartment model for diffusion tensor imaging. Neuroimage 103:323-33
Okonkwo, Ozioma C; Oh, Jennifer M; Koscik, Rebecca et al. (2014) Amyloid burden, neuronal function, and cognitive decline in middle-aged adults at risk for Alzheimer's disease. J Int Neuropsychol Soc 20:422-33
Mielke, Michelle M; Haughey, Norman J; Bandaru, Veera V R et al. (2014) Cerebrospinal fluid sphingolipids, ?-amyloid, and tau in adults at risk for Alzheimer's disease. Neurobiol Aging 35:2486-94
Fischer, Barbara L; Gleason, Carey E; Gangnon, Ronald E et al. (2014) Declining cognition and falls: role of risky performance of everyday mobility activities. Phys Ther 94:355-62
Johnson, Sterling C; Christian, Bradley T; Okonkwo, Ozioma C et al. (2014) Amyloid burden and neural function in people at risk for Alzheimer's Disease. Neurobiol Aging 35:576-84
Okonkwo, Ozioma C; Schultz, Stephanie A; Oh, Jennifer M et al. (2014) Physical activity attenuates age-related biomarker alterations in preclinical AD. Neurology 83:1753-60

Showing the most recent 10 out of 46 publications