Although functional and structural MRI have been used to characterize aging, disease, and cognition, the central nervous system mechanisms linking early mobility impairments to subsequent motor and cognitive decline remain under-explored. The current proposal investigates brain contributions to the clinically valuable measure of walking speed, a known predictor of incident falls, disability, and Alzheimer’s dementia and related dementias (ADRD) in older age. Several studies to date have found evidence that neurocognitive dysfunction and neurodegeneration result in slower walking. The observed relationships, however, are not consistent across studies. Structural investigations may or may not report relationships with impaired mobility; age-related declines of structure are variable, spatially diffuse, and cannot be fully captured in a single imaging modality. The applicant’s previous work has shown that brain function may be a promising predictor of gait and complementary to structural measures. However, because the majority of imaging investigations have been unimodal and cross-sectional, less is known about the neural mechanisms linking gait to future adverse health outcomes. This project combines complementary imaging data across multiple MR modalities to determine whether major neural drivers of motor function can be used to predict subsequent motor and cognitive decline, like disability and ADRD. Specifically, the applicant will: 1) develop an integrative model utilizing functional and structural MR biomarkers to predict cross-sectional gait and motor function within older adults from the Rush Alzheimer’s Disease Center Memory and Aging Project (MAP) and MOBILIZE Boston Study (MBS) cohorts, and 2) determine the extent to which these biomarkers may be used to predict future motor and cognitive decline, incident disability, and ADRD. For this project, the applicant’s central hypothesis is that subtle structural and functional compromise to regions belonging to the executive and attention neural networks link abnormal gait to motor and cognitive decline in older age. For this three-year Career Development Award, the applicant proposes to pursue these research aims and train in advanced statistical modeling and data science, physiologic and mobility measurement, and the neurobiology and neuropathology underlying mobility limitations, disability, and ADRD under the guidance of a multi-disciplinary multi-institutional team. The specific research and statistical modeling methods gained from this project supports the applicant’s long-term goal to inform successful aging for older adults by (1) investigating the neural mechanisms that contribute to functional impairments commonly encountered in older age, (2) identifying early biomarkers of these declines, and (3) developing neuroscience-informed interventions for improved outcomes.