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 discriminating healthy aging from early stage DAT, (b) predicting later conversion in a group of healthy middle-aged/older adults, and (c) showing relationships 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 accumulating 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 distributional 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 fluctuations 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 characteristics are related to the attentional control mechanisms, and modulate the brain-behavior relationships. The convergence across these aims, projects, and cores in the continuing 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 #
5P01AG026276-08
Application #
8522091
Study Section
Special Emphasis Panel (ZAG1-ZIJ-4)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
8
Fiscal Year
2013
Total Cost
$240,068
Indirect Cost
$82,128
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Roe, Catherine M; Ances, Beau M; Head, Denise et al. (2018) Incident cognitive impairment: longitudinal changes in molecular, structural and cognitive biomarkers. Brain 141:3233-3248
Ihara, Ryoko; Vincent, Benjamin D; Baxter, Michael R et al. (2018) Relative neuron loss in hippocampal sclerosis of aging and Alzheimer's disease. Ann Neurol 84:741-753
Sutphen, Courtney L; McCue, Lena; Herries, Elizabeth M et al. (2018) Longitudinal decreases in multiple cerebrospinal fluid biomarkers of neuronal injury in symptomatic late onset Alzheimer's disease. Alzheimers Dement 14:869-879
Xiong, Chengjie; Luo, Jingqin; Chen, Ling et al. (2018) Estimating diagnostic accuracy for clustered ordinal diagnostic groups in the three-class case-Application to the early diagnosis of Alzheimer disease. Stat Methods Med Res 27:701-714
Gabel, Matthew; Gooblar, Jonathan; Roe, Catherine M et al. (2018) Political Ideology, Confidence in Science, and Participation in Alzheimer Disease Research Studies. Alzheimer Dis Assoc Disord 32:179-184
Roe, Catherine M; Babulal, Ganesh M; Mishra, Shruti et al. (2018) Tau and Amyloid Positron Emission Tomography Imaging Predict Driving Performance Among Older Adults with and without Preclinical Alzheimer's Disease. J Alzheimers Dis 61:509-513
Musiek, Erik S; Bhimasani, Meghana; Zangrilli, Margaret A et al. (2018) Circadian Rest-Activity Pattern Changes in Aging and Preclinical Alzheimer Disease. JAMA Neurol 75:582-590
Aschenbrenner, Andrew J; Gordon, Brian A; Benzinger, Tammie L S et al. (2018) Influence of tau PET, amyloid PET, and hippocampal volume on cognition in Alzheimer disease. Neurology 91:e859-e866
Day, Gregory S; Gordon, Brian A; Perrin, Richard J et al. (2018) In vivo [18F]-AV-1451 tau-PET imaging in sporadic Creutzfeldt-Jakob disease. Neurology 90:e896-e906
Lewczuk, Piotr; Riederer, Peter; O'Bryant, Sid E et al. (2018) Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry. World J Biol Psychiatry 19:244-328

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