Brain Connectomics of Cognitive Aging and Vulnerability to Alzheimer's Disease - PROJECT SUMMARY The goal of this career development award is to provide me with the training necessary to develop an independent aging research program focusing on neuroimaging biomarkers and socioeconomic risk factors associated with differential aging trajectories and vulnerability to Alzheimer’s disease (AD), with the long-term goal of informing and improving risk prediction for AD and potential interventions and treatment to reduce AD risk. To achieve these goals, I propose to examine how alterations of brain functional and structural connectomes underlie cognitive aging and its longitudinal trajectories, and contribute to individual vulnerability to AD in cognitively normal individuals. Moreover, I propose to investigate how socioeconomic status may modulate the associations of brain connectomes with cognitive aging and risk for AD. My training to date has provided me with a strong methodological and theoretical foundation in cognitive neuroscience and neuroimaging, and advanced computational analyses to examine brain connectomes. My proposed training plan complements my existing expertise by providing training in the study of cognitive and brain aging, socioeconomic risk factors and biological processes and markers associated with aging and AD. Completion of the proposed research and training will enable my transition to independence and allow me to build an interdisciplinary aging research program that integrates neuroimaging, cognitive, and biological assessments. Research Project: Converging evidence has shown that connectivity and topological properties of brain connectomes underpin cognitive aging and contribute to the accumulation and spreading of AD pathologies. However, connectome-based (i.e., connectomic) biomarkers of cognitive aging trajectories have not been characterized in large-scale longitudinal studies, especially with regard to their potential in indexing early vulnerability to AD in cognitively unimpaired individuals. Moreover, there has been a lack of research on these topics in socially disadvantaged groups with high AD prevalence. The proposed project will address these critical research gaps using two large-scale longitudinal studies with cognitive, neuroimaging, and biological measures: Health and Aging Brain Study-Health Disparities and Vietnam Era Twin Study of Aging. Specifically, I will examine whether longitudinal changes in brain connectomes are associated with changes in multiple cognitive domains, serving as putative connectomic biomarkers of cognitive aging trajectories (Aim 1). I will then examine whether longitudinal changes in brain connectomes are associated with changes in levels of AD- related pathologies as measured from PET and plasma (Aim 2). Finally, I will examine whether low socioeconomic status (SES), an indicator of social disadvantage, modulates the associations between brain connectomes, cognition, and AD-related pathologies (Aim 3). The project will inform efforts aimed at establishing neuroimaging biomarkers for early identification of individuals at risk for cognitive impairment and AD, as well as understanding the role of SES in cognitive and brain aging and AD risk.
