In line with the mission of the National Institute on Aging, the proposed studies seek to use a mutli-method approach to improve early detection of Alzheimer?s disease (AD)-related cognitive aberrations, and to mitigate existing geographic, socioeconomic and health-related barriers in AD research by making these markers more widely accessible. Central to our project are two of our team?s mobile smartphone apps, which we will use to longitudinally track autobiographical thoughts in everyday life. Extending our previous work in this area, our proposed studies will a) examine how real-world autobiographical thoughts in cognitively unimpaired young, middle-aged, and older adults are altered by the presence of a key genetic risk factor for AD, namely the apolipoprotein E e4 allele (APOE4), b) uncover the neural underpinnings of such alterations among older adults and relationships between cognitive and neural changes over time, c) reveal the prognostic potential of measuring autobiographical thoughts in older adults for a host of longitudinal health outcomes suggestive of the preclinical progression of AD, and d) shed light on neurocognitive characteristics associated with normal ?low- risk? aging. MPIs Dr. Grilli and Dr. Andrews-Hanna have formed a team of researchers with expertise in naturalistic assessment of cognition, autobiographical thought, resting state functional connectivity, healthy and pathological aging, and longitudinal analysis of large datasets. Utilizing our team?s interdisciplinary expertise, we will execute an innovative two-pronged project harnessing in-lab, at-home, and online assessment methods that will evaluate the relationships of AD risk and aging to the autobiographical thoughts of >1,225 genotyped cognitively unimpaired adults, with a subset completing additional in-lab experimental tests, neuroimaging, and longitudinal follow-up.
In Aim 1, we will test the hypothesis that autobiographical thoughts assessed in real-world settings are particularly sensitive to increased AD risk, as measured by APOE4, among cognitively unimpaired adults, and that alterations in resting state functional connectivity of the default network mediate these AD risk- cognitive relationships.
Aim 2 tests the hypothesis that measures of real-world autobiographical thoughts are better predictors than lab-based tests of future neural (i.e., default network resting state functional connectivity), cognitive, affective (i.e., depressive symptoms), and functional changes (i.e., instrument and social functioning) suggested by preclinical AD acceleration.
Aim 3 uncovers changes in autobiographical thoughts and their underlying neural architecture that emerge from normal (i.e., low AD-risk) aging. This project is both significant and innovative; to our knowledge, it will be the first to use smartphones to track autobiographical thoughts as a means to identify AD risk, despite strong theoretical tenets and preliminary evidence that doing so could improve precision of cognitive estimation and tap into cognitive operations that tax the primary brain pathway of AD. Ultimately, our mobile tools may lead to accessible cognitive tests of increased risk for AD and perhaps key preclinical markers of AD (i.e., amyloid and tau), with broad impact for clinicians and patients worldwide.

Public Health Relevance

The proposed research is relevant to public health because improved early cognitive detection of one?s risk for developing Alzheimer?s disease dementia is essential for proactive and effective treatment of this disease, which is the sixth leading cause of death for older Americans. This research aligns with the National Institute on Aging?s 21st Century strategic direction to ?better understand the biology of aging and its impact on the prevention, progression, and prognosis of disease and disability.? By using mobile tools to assess cognition naturalistically, the proposed studies may increase accessibility of cognitive assessment, improve early detection of risk for and preclinical signs of Alzheimer?s disease, and reveal new cognitive endpoints for prevention therapies.

National Institute of Health (NIH)
National Institute on Aging (NIA)
High Priority, Short Term Project Award (R56)
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Cognition and Perception Study Section (CP)
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Plude, Dana Jeffrey
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University of Arizona
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