There is accumulating evidence of a breakdown in attentional control systems and consequent increases in reaction time (RT) variability that may reflect a prodromal stage of Alzheimer's disease (AD). Recent evidence indicates that tasks which place a high load on attentional systems are particularly useful in (a) serving as a behavioral marker in discriminafing healthy aging from early stage DAT, (b) predicfing later conversion in a group of healthy middle-aged/older adults, and (c) showing relafionships with other biomarkers in healthy control individuals. The proposed research will continue to longitudinally follow the adult child sample, who have well-characterized risk for developing symptomatic AD, to address the following issues: First, we will examine a set of cognitive tasks that target attentional selection, executive control, and attentional control contributions to memory performance and relate these measures to the accumulafing biomarkers from the other projects and cores (e.g., PIB, CSF measures, AP0E4 status, structural and resting state fMRI measures). Second, we will explore subtle characteristics of RT distribufional performance utilizing ex-Gaussian analyses and the diffusion model to examine the extent to which distinct parameters are useful prodromal markers for risk for developing AD. Third, we will use both a Sustained Attention to Respond task (SART) and a simple repetitive finger tapping task as behavioral markers for momentary fiuctuafions in task disengagement to irrelevant thoughts (i.e., mind wandering). Fourth, we will measure the task related neural response (via fMRI) in both a Stroop and Encoding Subsequent Memory paradigm to determine if attentional and/or default mode neural networks begin to be compromised before there is disruption in cognitive performance and relate these results to the biomarkers developing in the other projects, especially the resting state fcMRI studies in Project 4. Fifth, we will examine the extent to which personality characterisfics are related to the attenfional control mechanisms, and modulate the brain-behavior relafionships. The convergence across these aims, projects, and cores in the confinuing longitudinal study of the Adult Children Study cohort affords a unique opportunity to develop an understanding of the multi-faceted nature of the earliest bio-behavioral changes associated with AD.

Public Health Relevance

The focus of the current research (including this PPG) is heavily weighted toward discovery of predictive and diagnostic Alzheimer biomarkers involving behavior, modeling, and imaging. This project links the most promising AD biomarkers with equally promising cognitive-behavioral markers to complement and improve putative biomarkers and advance basic understanding of the AD process.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
2P01AG026276-06A1
Application #
8287323
Study Section
Special Emphasis Panel (ZAG1-ZIJ-4 (01))
Project Start
2011-09-30
Project End
2016-08-31
Budget Start
2011-09-30
Budget End
2012-08-31
Support Year
6
Fiscal Year
2011
Total Cost
$205,797
Indirect Cost
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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