Neuroimaging Markers of Emerging Dysfunction In Preclinical Alzheimer Disease

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The objective of this proposal is to support the candidate's development and transition into an independent researcher. The outlined training plan will equip the applicant with the necessary skills to conduct innovative work that spans both primary research and clinical domains. The accrual of Alzheimer's disease (AD) pathology can begin decades before the onset of cognitive symptoms. Higher levels of pathology increase the risk of dementia, but the relationship between pathology and cognition is imperfect. Functional magnetic resonance imaging (fMRI) provides a way to non-invasively assess the integrity of networks in the brain that support cognition. As such it may provide a better measure of the brain's health than biomarkers of pathology alone. Prior work using fMRI has almost exclusively utilized only episodic memory tasks. This approach is limited as AD leads to deficits beyond memory domains. The goal of Aim 1 is to characterize alterations in neural activity related to preclinical levels of AD pathology using three tasks that respectively target attentional control, working memory, and episodic memory. The goal of Aim 2 is to compare the sensitivity of these task-based fMRI paradigms to resting-state fMRI. The goal of Aim 3 is to relate task-based fMRI data to longitudinal cognition and the transition from cognitive normality to an impaired state. This work will improve our understanding of the relationship between AD pathology and neuronal activity, as well as the relationship between such fMRI activity and longitudinal cognition.