The Adult Children Study (ACS) is an ongoing evaluation of middle to older adults at risk for development of Alzheimer disease (AD). In Project 4 of the ACS, we use a combination of advanced imaging techniques to explore the earliest signs of AD pathology. Using positron emission tomography (PET) we test for amyloid protein deposits in the brain, which can be present up to 20 years before dementia symptoms are present. We will do this using florbetapir F18, which is a test for amyloid which has approval by the Federal Food and Drug Administration (FDA). Using magnetic resonance imaging (MRI) we evaluate the functional changes in the brain associated with the transition from the asymptomatic (preclinical) stages of AD into the symptomatic stage of AD dementia. We also use MRI to evaluate the brain?s structure, looking at grey matter atrophy with volumetric MRI, and investigate the changes in white matter using a new technique, diffusion basis spectrum imaging (DBSI). In collaboration with Project 4, in Aim 1, we will generate unique brain maps for each imaging test, in each stage of AD, as people move from an asymptomatic state into AD dementia.
In Aim 2, we will then examine these maps in relation to one another, to develop an integrated timeline for the imaging changes which occur during the transition from asymptomatic and symptomatic AD. We will then use these maps as a way to predict the stage of the disease in specific individuals ? in other words, to predict how long it would be before someone developed dementia. This mapping and predictive information is critical for the development of new drugs for AD and for the appropriate design of clinical trials in the future.

Public Health Relevance

Using brain imaging scans, we are able to identify people who have Alzheimer disease (AD) pathology many years before symptoms develop but we are not able to predict when someone will transition from a normal state into dementia. In Project 4, we have assembled an advanced set of imaging tests to examine the earliest stages of AD, in order to develop predictions of when, or if, dementia might begin, which can significantly improve clinical trials and treatment designs in the future.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG026276-15
Application #
9963101
Study Section
Special Emphasis Panel (ZAG1)
Project Start
Project End
Budget Start
2020-06-01
Budget End
2021-05-31
Support Year
15
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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