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

项目摘要 我们迅速老龄化的人口仍然处于使人衰弱的福尔斯的极高风险之中。这一点尤其令人担忧， 痴呆症的复合效应特别地，路易体痴呆症（DLB）独特地与脑卒中相关。 福尔斯患病率增加。开发一个改进的机制框架，以了解平衡障碍，由于 年龄老化和DLB以减轻福尔斯风险是该提案的核心。站立和行走平衡的神经力学 控制，以及因此由于老化和DLB导致的平衡受损的起源是非常复杂的。主动响应 在平衡挑战开始之前，通过前馈控制使身体准备好适应不稳定性。 相反，反应性反应在平衡挑战开始后出现，并且是补偿性的，需要快速纠正， 缓解不稳定。这项奖学金提案的首要科学前提是，衰老对反应性 平衡反应，而年龄和认知能力下降的复合效应对主动平衡反应产生负面影响 在DLB患者中，从而增加了对可能加速福尔斯的现实世界平衡挑战的脆弱性。十字架- 部分研究将招募25名年轻人，25名老年人，临床上可能的DLB，和25名年龄和性别， 匹配老年人。我将战略性地将联合收割机定量动作捕捉，肌电图，动态活体 超声成像和可穿戴传感器，具有创新的站立和行走扰动范例套件， 模拟现实世界的平衡挑战。目标1将确定年龄和LBD对全身易感性的影响， 站立和行走时的预期和非预期平衡挑战。目标2将表征局部肌肉 这些队列中反应性和主动性平衡反应的神经力学决定因素。最后，社区- 基于翻译作为我的科学和专业发展的最终目标，目标3将量化的可行性 可穿戴传感器，以监测和检测群体之间对扰动的脆弱性差异。本研究将 第一个客观量化组间差异的多尺度特征的积极和消极的平衡 使用基于实验室和基于可穿戴传感器的结果进行响应，旨在将我的发现从实验室转移到 到诊所和社区。这一领域的机制和假设驱动的研究一直严重不足， 但具有重要和直接的潜力，可以为诊断、康复、移动的监测和 穿戴式辅助技术来减轻福尔斯的摔倒。

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.