The Proactive and Reactive Neuromechanics of Instability in Aging and Dementia with Lewy Bodies

PROJECT SUMMARY Our rapidly aging population remains at an exceptionally high risk of debilitating falls. This is especially concerning given the compounding effects of dementia. In particular, Dementia with Lewy Bodies (DLB) is uniquely associated with an increased prevalence of falls. Developing an improved mechanistic framework to understand balance impairment due to age aging and DLB to mitigate falls risk is at the heart of this proposal. The neuromechanics of standing and walking balance control, and thus the origins of balance impairment due to aging and DLB, are incredibly complex. Proactive responses precede the onset of a balance challenge via feedforward control to prepare the body to accommodate instability. Conversely, reactive responses follow the onset of a balance challenge and are compensatory, requiring rapid corrections to mitigate instability. The overarching scientific premise of this fellowship proposal is that aging negatively affects reactive balance responses, while the compounding effects of age and cognitive decline negatively affect proactive balance responses in people with DLB, thus increasing vulnerability to real-world balance challenges that can precipitate falls. This cross- sectional fellowship study will enroll 25 young adults, 25 older adults with clinically probable DLB, and 25 age- and sex- matched older adults. I will strategically combine quantitative motion capture, electromyography, dynamic in vivo ultrasound imaging, and wearable sensors with an innovative suite of standing and walking perturbation paradigms designed to emulate real-world balance challenges. Aim 1 will determine the effects of age and LBD on whole-body vulnerability to anticipated and unanticipated balance challenges during standing and walking. Aim 2 will characterize the local muscle neuromechanical determinants of reactive and proactive balance responses across these cohorts. Finally, with community- based translation as the ultimate goal of my scientific and professional development, Aim 3 will quantify the viability of wearable sensors to monitor and detect between-group differences in vulnerability to perturbations. This study will be the first to objectively quantify between-group differences in multi-scale characteristics of proactive and reactive balance responses using laboratory-based and wearable-sensor based outcomes designed to move my discoveries from the laboratory to the clinic and the community. This area of mechanistic and hypothesis-driven research has been severely understudied, but has significant and immediate potential to inform novel advances in diagnostics, rehabilitation, mobile monitoring, and wearable assistive technologies to mitigate falls.