Cerebral Small Vessels in Motor and Cognitive Decline: Neuroimaging Signatures of Vulnerability & Resilience

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SUMMARY White matter hyperintensities (WMH), which are increasingly more prevalent on brain MRIs, are significantly associated with vascular risk factors and linked to age-related mobility and cognitive impairment. However, not everyone with WMH is equally afflicted and some older individuals are able to maintain their mobility and cognition despite a significant burden of WMH on their brain MRI. We do not know what specific attributes of these individuals contribute to their resilience. Identifying which specific factors are associated with cognitive vulnerability and/or resilience in the presence of WMH is critical for favorably impacting the trajectory of brain health in our aging population, especially among health disparity populations. Over the past 5 years we have been able to identify neuroimaging features associated with vascular risk factors, gait and cognition in midlife. Building on these findings, we now propose to continue our line of inquiry and identify the neuroimaging features associated with gait and cognitive performance in mid- to late-life individuals with WMH, with a specific focus on African Americans and women, both of whom are at a high risk for developing WMH, gait and cognitive impairment, but have often been under-represented in such studies. In Aim1, we will characterize the diffusion properties of the normal appearing white matter (NAWM) and resting brain functional network connections in mid- to late-life individuals who have WMH. These are the neuroimaging features that we have already identified in our midlife cohort study. In Aim 2 we will determine how changes in diffusion properties of NAWM and resting brain function network connections change in relation to gait and cognition in mid- to late life individuals with WMH. Aim3 is an exploratory aim to identify other attributes associated with maintaining gait and cognitive performance in mid- to late-life individuals who display WMH on brain MRI. Findings from the proposed work, will serve two overarching objectives. First, identified neuroimaging features that associate with gait and cognitive performance in individuals with WMH will help guide treatment decisions and allocation of appropriate individuals with WMH for future clinical trials. Second, identified neuroimaging features that associated with gait and cognitive vulnerability &/ or resilience in the presence of WMH will reveal underlying mechanisms and facilitate the future possibility of therapeutic development targeted at mitigating progression to impaired mobility and dementia and expression of Alzheimer’s Disease and related Dementias (ADRD) in at- risk individuals.