Brain anatomical correlates of mobility control in the oldest old

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DESCRIPTION (provided by applicant): Community-dwelling older adults often report mobility impairment linked with multifactorial changes in the cardiopulmonary, musculoskeletal, peripheral and central nervous systems. There is strong emergent evidence that white matter (WM) hyperintensities are associated with lower-extremity mobility limitations independent of other factors. Dr. Rosano has recently discovered that impaired speed and balance are associated with focal grey matter (GM) atrophy of specific mobility-related regions. This longitudinal epidemiological project aims to investigate the longitudinal association of focal brain magnetic resonance imaging (MRI) abnormalities in GM and WM with age-related mobility impairment in gait speed and balance in a large cohort of community-dwelling older adults from the Health Aging Body Composition Study (Health ABC). This proposal builds onto the current ongoing Healthy Brain Project (K23AG028966-01, PI: Dr Rosano), which is a descriptive cross-sectional study of the association between quantitative brain MRIs measures and mobility in 250 participants of the Health ABC cohort. The new study that we propose will increase the power to detect important effects via the acquisition of additional 148 MRIs and will provide further longitudinal insights into the impact of brain MRI abnormalities on the natural history of mobility impairment by adding a follow up time of 3 years after completion of brain MRI. Thus, this proposal is uniquely timed to capture important information during the planned data collection phase of the Health ABC Study in 2006-2007. This project uses automated volumetric methods, magnetization transfer and diffusion tensor imaging to measure severity and location of GM and WM abnormalities. The aims of this project are: 1. To examine the longitudinal association of focal regional GM and WM tracts abnormalities with worsening mobility and specifically with gait speed and balance. 2. To examine the combined effect of groups of GM/ WM abnormalities on worsening speed and balance. 3. To determine the longitudinal association of cardiovascular risk factors with focal GM and WM abnormalities in mobility-related regions and tracts. The results of this project will advance our knowledge of the pathogenesis of mobility impairment in community-dwelling older adults and will lay the ground work for further studies of age-related changes of the neural networks involved in mobility control, for example using functional brain MRI studies.