Project R-5 – Dr. Andrew Bender

Alzheimer’s disease (AD) is the most common cause of dementia, affecting millions of older U.S. adults. Critically, some people with higher risk for AD or with measurable brain atrophy and elevated AD biomarkers do not show cognitive impairment. Such cognitive resilience to neurodegeneration is poorly understood, but current scientific perspectives suggest it may be due to changes in connectivity of the brain’s networks. However, prior studies of cognitive resilience have not evaluated longitudinal changes between functional and structural brain networks. Project 5 will evaluate longitudinal patterns of coupling between dynamic functional connectivity (dFC) and white matter structural connectivity in older adults at risk for AD to better understand brain changes associated with cognitive resilience. The project will leverage existing longitudinal data from participants clinically diagnosed as cognitively unimpaired (CU) or with mild cognitive impairment (MCI), enrolled in the Center for Neurodegeneration and Translational Neuroscience (CNTN).

Using data from resting state functional MRI (RS-fMRI) and diffusion MRI (dMRI), the project will model interactions between dynamic functional connectivity and structural connectivity. The project will examine cognitive resilience based on 1) longitudinal trajectories of performance on neuropsychological tests and the modifying influences of individual and combined AD risk factors. Data analysis will use advanced latent factor modeling techniques to assess dFC and structural connectivity as combined predictors of change in cognitive function in the presence of AD risk. We hypothesize dFC–white matter network coupling is normally attenuated by elevated AD risk, but that such coupling is maintained in those exhibiting higher levels of cognitive resilience. This project is expected to provide critical evidence that interactions between structural and functional brain networks underlie differences in cognitive resilience. The project will generate preliminary data for new funding proposals for larger-scale investigations from multiple ongoing studies of AD risk provide new neuroimaging measures of functional and structural connectivity and neurodegeneration for use by CNTN collaborators.