This proposal leverages and extends the MOBILIZE Boston Study (MBS), which previously demonstrated significant relationships between abnormal cerebral blood flow (CBF) regulation, slow gait speed, and the development of falls in a representative population of elderly people living in the Boston metropolitan area. Our findings have led to the hypothesis that alterations in CBF regulation are associated with microvascular damage to periventricular and subcortical white matter in the brain, which ultimately results in slowing of gait, executive dysfunction, and falls. We also hypothesize that those individuals who can redistribute blood flow to healthy cortical networks during cognitive or motor tasks can prevent slowing of gait and falls, despite the presence of white matter damage. The current proposal will add rigorous transcranial Doppler and neuroimaging (structural, diffusion tensor, and functional MRI) measures to the third assessment of 250 MBS participants to determine whether: 1) reduced CBF in response to a cognitive or motor task (neurovascular coupling), is longitudinally associated with the slowing of gait speed, executive dysfunction, functional decline, and recurrent falls over 2 years of followup;2) abnormalities in CBF regulation, including CO2 vasoreactivity and neurovascular coupling, are associated with loss of white and gray matter microstructural integrity on MRI and diffusion tensor imaging (DTI);3) these structural changes in the brain are associated with slowing of gait, executive dysfunction, functional decline, and recurrent falls over 2 years;and 4) the brain's ability to increase blood flow to healthy regions during cognitive or motor tasks can attenuate the adverse effects of white or gray matter microstructural damage on functional decline and falls. The study is unique in focusing on alterations in CBF as a pathological mechanism of falls, developing cutting-edge MR imaging techniques to detect early microstructural markers of brain damage that can predict falls, and identifying a compensatory mechanism that protects some people from the effects of this damage on falls - all in a large representative elderly cohort. Our successful 7-year retentio and followup of the MBS cohort and collaboration with the Boston VA Neuroimaging Center will help assure we achieve our goals. Relevance: This study will provide novel information necessary for the early detection and ultimate prevention of cerebrovascular causes of falls and mobility impairments in elderly people. If abnormal brain blood flow is discovered to be a cause of falls, currently available interventions to increase brain blood flow, prevent cerebrovascular damage, grow new blood vessels, or build new neural pathways may prevent future falls.
This study explores alterations in cerebral blood flow as a pathological mechanism of falls, develops cutting-edge magnetic resonance imaging techniques to detect early microstructural markers of brain damage that can predict falls, and identifies a compensatory mechanism that protects some people from the effects of this damage on falls - all in a large representative elderly cohort of the MOBILIZE Boston Study. The study will provide new information necessary for the early diagnosis and ultimate prevention of cerebrovascular causes of falls and mobility impairments in elderly people.