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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
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Special Emphasis Panel (ZAG1-ZIJ-4)
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Washington University
Saint Louis
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Su, Yi; Blazey, Tyler M; Snyder, Abraham Z et al. (2015) Partial volume correction in quantitative amyloid imaging. Neuroimage 107:55-64
Yap, Melvin J; Sibley, Daragh E; Balota, David A et al. (2015) Responding to nonwords in the lexical decision task: Insights from the English Lexicon Project. J Exp Psychol Learn Mem Cogn 41:597-613
Aschenbrenner, Andrew J; Balota, David A; Tse, Chi-Shing et al. (2015) Alzheimer disease biomarkers, attentional control, and semantic memory retrieval: Synergistic and mediational effects of biomarkers on a sensitive cognitive measure in non-demented older adults. Neuropsychology 29:368-81
Harari, Oscar; Cruchaga, Carlos; Kauwe, John S K et al. (2014) Phosphorylated tau-A?42 ratio as a continuous trait for biomarker discovery for early-stage Alzheimer's disease in multiplex immunoassay panels of cerebrospinal fluid. Biol Psychiatry 75:723-31
Jin, Sheng Chih; Benitez, Bruno A; Karch, Celeste M et al. (2014) Coding variants in TREM2 increase risk for Alzheimer's disease. Hum Mol Genet 23:5838-46
Ringman, John M; Goate, Alison; Masters, Colin L et al. (2014) Genetic heterogeneity in Alzheimer disease and implications for treatment strategies. Curr Neurol Neurosci Rep 14:499
Thomas, Jewell B; Brier, Matthew R; Bateman, Randall J et al. (2014) Functional connectivity in autosomal dominant and late-onset Alzheimer disease. JAMA Neurol 71:1111-22
Benitez, Bruno A; Jin, Sheng Chih; Guerreiro, Rita et al. (2014) Missense variant in TREML2 protects against Alzheimer's disease. Neurobiol Aging 35:1510.e19-26
Fagan, Anne M; Xiong, Chengjie; Jasielec, Mateusz S et al. (2014) Longitudinal change in CSF biomarkers in autosomal-dominant Alzheimer's disease. Sci Transl Med 6:226ra30
Brier, Matthew R; Thomas, Jewell B; Fagan, Anne M et al. (2014) Functional connectivity and graph theory in preclinical Alzheimer's disease. Neurobiol Aging 35:757-68

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