Neuroplasticity and cerebral blood flow as key resilience mechanisms in the brains of fast-moving SuperAgers

Project Summary: The gradual loss of physical and cognitive ability has been taken as the near-universal consequence of growing older. Older adults slow down physically, with reduced gait speed and increased instability, and slow cognitively, with declining memory and executive function. Disease pathologies can accelerate these declines and are the focus of most aging research. Nonetheless, exceptions to these trajectories can be identified, most notably cognitive “SuperAgers,” who retain the working memory of people 30 years younger. Initial research on SuperAgers has focused only on cognition studied through static, MR- based neuroimaging and cytoarchitectural examination of post-mortem brains. However, as mounting evidence demonstrates fast movement is a distinguishing feature of health and longevity in older adults, our research emphasizes the dynamic interaction between brain neural and vascular function during physical movement. Our preliminary data illustrate that older adults age 75+ years with exceptionally fast walking speeds and who are free of cognitive decline – who we have termed fast-moving SuperAgers - display a robust capacity for neuroplasticity induction (measured with electroencephalography (EEG)) and remarkably high cerebral blood flow (measured with transcranial Doppler ultrasound (TCD)) during whole-body behavioral learning. Motivated by these captivating data, this DP2 project will test the novel hypothesis that fast-moving SuperAgers are enriched in unique neuroplasticity and cerebrovascular profiles that are neuroprotective and enable remarkably high physical and cognitive function as they near or enter their 9th and 10th decade. This project embraces a systems-neuroscience perspective to study neuroplasticity induction and interactions with real-time cerebrovascular function in the unique aging phenotype of fast-moving SuperAgers. We utilize a highly innovative, multimodal approach (EEG, biomechanics, TCD) to quantify the adaptation of cortical and biomechanical responses to repeated standing balance perturbations. We synergistically assess real-time cerebral blood flow velocity during this balance learning task and interactions with cortical plasticity induction. We will compare the state and longitudinal trajectory of neuroplasticity and cerebrovascular function in fast- moving SuperAgers to their normally- and slow-moving peers under the same learning conditions. These results could identify key functional neuroprotective mechanisms of brain aging to be leveraged and targeted with future interventions to prevent decline of cognition and physical function. The development of targeted, physiologically-informed interventions through a lens of brain resilience for neurodegenerative diseases such as dementia would be especially impactful because current pathology-focused treatments (e.g. anti-amyloid drugs) are extremely limited. Findings gleaned through our innovative conceptual and technical approach to study human aging neurobiology could pave the way towards a new resilience-focused framework, enabling us to make impactful scientific discoveries to improve the lives of aging Americans.