Project 462111

Background: Social inequality in North America is at its highest documented level of the past century. Emerging from our recent work in homeless and vulnerable housed persons is the powerful contribution of frequent TBI and early brain vascular disease to negative health outcomes. Cognitive changes and Brain MRIs in our participants show a pattern of early, deleterious brain changes associated with a history of TBI and brain vascular disease, the risk factors for which differ from the general population. We have been following a cohort of over 500 vulnerable housed persons for more than 10 years, developing a comprehensive, granular clinical data pipeline that involves longitudinal neuropsychiatric assessments, granular substance use trajectories and brain MRI. Our goal is to identify drivers of disability that ultimately reveal modifiable mechanisms contributing to poor outcomes so as to inform effective interventions. AIM: Over the next 5 years, to understand how TBI and cerebral small vessel disease (a component of the cerebro-vascular system that supplies the brain's white matter and other structures) interface to affect neurofunctional decline and brain structural changes suggestive of neurodegeneration. An additional aim is to explore the feasibility of using multimodal biomarkers to address the assessment and diagnostic challenges of neurocognitive decline in homeless and vulnerable housed populations. By harnessing state-of-the-art clinical phenotyping, neuroimaging and blood biomarker technology we are in a unique position to characterize the extent of the problem, discern mechanisms, risks and protective factors to immediately inform meaningful interventions. Significance: Homeless populations are ageing and degenerative diseases of the brain are appearing more frequently. For individual health and for public policy understanding the risk factors for poor brain health in our poorest peoples is vitally important.