Insights into Cognitive Resilience: Sleep, Physical Activity, and Neuroimaging Biomarkers in Aging and Preclinical Alzheimer's Disease

This Mentored Patient-Oriented Research Career Development Award (K01) application aims to equip the candidate with the skills to establish an independent research program identifying modifiable lifestyle factors to enhance cognitive resilience in aging and Alzheimer's disease-related dementias (ADRDs) and develop neuroimaging measures to quantify these relationships. The proposed research will examine (1) actigraphy- based measures of physical activity and sleep, and (2) network neuroimaging-based measures of functional connectivity and microstructural integrity, as potential synergistic correlates of cognitive trajectories in older adults and those with AD pathology accumulation. Recent published work by the candidate suggests physical activity and sleep are synergistically related to better cognition and neuroimaging measures of functional connectivity and microstructural integrity, and that these neuroimaging measures may reflect mechanisms of cognitive resilience in aging and AD cross sectionally. This application proposes a longitudinal study to assess i) whether physical activity and sleep are factors associated with cognitive resilience to AD pathology accumulation over time, ii) if brain network connectivity and microstructure are neuroimaging correlates of cognitive resilience to AD pathology over time, and iii) the association between physical activity and sleep with functional connectivity and microstructure over time. With an excellent multidisciplinary mentorship team, the applicants career development plan builds on his research training to gain experience in 1) AD pathology biomarkers (specifically Positron Emission Tomography and Cerebrospinal Fluid), 2) actigraphy based measures of physical activity and sleep, 3) longitudinal statistical analysis, 4) theoretical training in cognitive resilience research and clinical knowledge of AD and related disorders, 5) professional development, and 6) responsible conduct of research. The research objectives and training goals will foster an exceptional learning environment, advancing the candidate's knowledge in cognitive aging and ADRD, ultimately facilitating their transition to an independent investigator exploring the impact of modifiable lifestyle activities and brain mechanisms underlying cognitive resilience in older individuals.