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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La Joie, Renaud; Bejanin, Alexandre; Fagan, Anne M et al. (2018) Associations between [18F]AV1451 tau PET and CSF measures of tau pathology in a clinical sample. Neurology 90:e282-e290
Broce, Iris; Karch, Celeste M; Wen, Natalie et al. (2018) Correction: Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies. PLoS Med 15:e1002504
Liao, Fan; Li, Aimin; Xiong, Monica et al. (2018) Targeting of nonlipidated, aggregated apoE with antibodies inhibits amyloid accumulation. J Clin Invest 128:2144-2155
Yan, Qi; Nho, Kwangsik; Del-Aguila, Jorge L et al. (2018) Genome-wide association study of brain amyloid deposition as measured by Pittsburgh Compound-B (PiB)-PET imaging. Mol Psychiatry :
Strain, Jeremy F; Smith, Robert X; Beaumont, Helen et al. (2018) Loss of white matter integrity reflects tau accumulation in Alzheimer disease defined regions. Neurology 91:e313-e318
Li, Zeran; Del-Aguila, Jorge L; Dube, Umber et al. (2018) Genetic variants associated with Alzheimer's disease confer different cerebral cortex cell-type population structure. Genome Med 10:43
Schindler, Suzanne E; Sutphen, Courtney L; Teunissen, Charlotte et al. (2018) Upward drift in cerebrospinal fluid amyloid ? 42 assay values for more than 10 years. Alzheimers Dement 14:62-70
Sato, Chihiro; Barthélemy, Nicolas R; Mawuenyega, Kwasi G et al. (2018) Tau Kinetics in Neurons and the Human Central Nervous System. Neuron 98:861-864
Babulal, Ganesh M; Chen, Suzie; Williams, Monique M et al. (2018) Depression and Alzheimer's Disease Biomarkers Predict Driving Decline. J Alzheimers Dis 66:1213-1221
Millar, Peter R; Balota, David A; Bishara, Anthony J et al. (2018) Multinomial models reveal deficits of two distinct controlled retrieval processes in aging and very mild Alzheimer disease. Mem Cognit 46:1058-1075

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