Project 4 will leverage the increasing popularity of smartphones to improve upon standard in-clinic cognitive testing, providing a robust characterization of cognition in participants enrolled in the Healthy Aging and Senile Dementia PPG. One of the most important and face-valid indicators of Alzheimer disease (AD) is a change in cognition, but assessing cognition in-clinic has several drawbacks. First, performance is influenced by day-to- day fluctuations in stress, fatigue, sleep patterns, and mood. Second, the testing takes place in environments that are fundamentally different from where cognitively demanding tasks are performed in daily life. Finally, by design, cognition is typically assessed very infrequently, usually once per year (as currently is the case in HASD). One solution would be to increase the frequency of in-clinic testing or to complete assessments in the natural environments in which participants use cognition such as their homes, workplaces, while traveling, etc., but this is impractical and burdensome, especially for older adults. Project 4 will provide a solution to these difficulties by taking advantage of the increasing popularity of smartphones. Smartphone usage is climbing in every age category, and even in older adults, 50% have and regularly use internet-enabled smartphones. In Project 4, we have designed an iOS and Android app called the Ambulatory Research in Cognition (ARC) app that will be installed on HASD participants' personal smartphones. If participants do not own a smartphone or have an antiquated model, we will provide a study phone for use while enrolled. Every six months, participants will complete extremely brief (<3 minutes each) testing sessions 4x/day over the course of one week. Tests are averaged across the week to provide a score that captures and normalizes natural variability and dramatically increases reliability. Pilot studies show that ARC assessments demonstrate extraordinary reliability, ranging from 0.92 to 0.99. Another advantage is the ability to measure variability within a day, across a week, and across the 6-month intervals of assessments. We hypothesize that ARC assessments will be more sensitive than in-clinic assessments to disease stage and AD biomarkers and that amyloid-positive HASD participants will show more variability in cognitive performance than amyloid-negative participants, even in the preclinical stages of disease. If successful, the increases in sensitivity and reliability of ARC assessments will provide extraordinary statistical power to characterize cognitive decline in observational studies of AD. In addition, ARC assessments could benefit clinical trials by shortening trial duration and requiring fewer participants.

Public Health Relevance

People rely on cognitive abilities to function in situations and natural environments experienced in daily life, but research studies assess cognition in ?one shot? in a laboratory or clinical setting, which can yield unreliable results. This Project will use a smartphone app to assess cognition with several brief (<3 min) tests per day over the course of a week in people at risk for and with symptomatic Alzheimer disease (AD). If successful, this study will provide new insights into AD and could lead to faster results from clinical trials.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
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Special Emphasis Panel (ZAG1)
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Washington University
Saint Louis
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Schultz, Stephanie A; Gordon, Brian A; Mishra, Shruti et al. (2018) Widespread distribution of tauopathy in preclinical Alzheimer's disease. Neurobiol Aging 72:177-185
Ibanez, Laura; Dube, Umber; Davis, Albert A et al. (2018) Pleiotropic Effects of Variants in Dementia Genes in Parkinson Disease. Front Neurosci 12:230
Javaherian, Kavon; Newman, Brianne M; Weng, Hua et al. (2018) Examining the Complicated Relationship Between Depressive Symptoms and Cognitive Impairment in Preclinical Alzheimer Disease. Alzheimer Dis Assoc Disord :
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
Jansen, Willemijn J; Ossenkoppele, Rik; Tijms, Betty M et al. (2018) Association of Cerebral Amyloid-? Aggregation With Cognitive Functioning in Persons Without Dementia. JAMA Psychiatry 75:84-95
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
Islam, Jyoti; Zhang, Yanqing (2018) Brain MRI analysis for Alzheimer's disease diagnosis using an ensemble system of deep convolutional neural networks. Brain Inform 5:2
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 :
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
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

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