Investigating cerebrovascular regulation during exercise as a factor influencing cortical resource engagement for balance control with aging

项目摘要/摘要 在老化过程中，失去了平衡和机动性中的自动性，其中 平衡控制的皮质资源可能会干扰老年人进行认知和平衡的能力 行为同时发生。在正常衰老的过程中，脑血流量会下降，这是 与老年人的认知功能受损有关。然而，目前还不清楚是否与年龄有关 脑血管和神经系统功能下降可能相互作用，表现为认知障碍 导致跌倒和临床痴呆的平衡控制。此外，携带载脂蛋白的老年人 E4(APOE4)等位基因，已知的阿尔茨海默病最大的遗传风险因素，显示出更大的 脑血管功能障碍与年龄匹配的非携带者相比，表现出更差的平衡能力 在认知负荷条件下，支持个体基因对之间的联系的潜在影响 脑血管健康和随年龄增长的平衡控制。 使用脑电(EEG)测量站立平衡反应期间的动态皮质活动， 候选人最近的研究结果提供了一个个性化的大脑皮层参与框架 老年人的平衡控制策略与平衡行为和跌倒的不同方面相关 风险，包括对平衡表现的认知干扰。目前，临床研究的一个主要科学障碍 这项研究的翻译是缺乏对影响个体特定皮质的因素的了解 应对衰老的平衡控制策略。新出现的证据表明，随着年龄的增长，认知障碍可能会 由脑血流功能障碍引起的，具体表现为脑血管调节受损 在生理应激条件下。对急性有氧运动的脑血流反应迟钝， 比林格博士(主要导师)和她的实验室开创了一种评估方法，似乎是一个早期的 临床前老年人群脑血管调节功能障碍的指标。建议数 该项目将首次测试急性有氧运动期间脑血管调节之间的联系 运动，用经颅多普勒超声测量脑血流速度，皮质 用认知双任务平衡成绩(AIM)测量衰老平衡行为过程中的功能 1)和脑电测量平衡反应期间的皮质活动(目标2)。一个探索性的目标将检验 载脂蛋白4基因携带者状态改变脑血管调节与平衡控制的关系 上了年纪的人。从这些研究中获得的科学知识将为 了解心血管-神经系统的相互作用可能有助于老年人的平衡障碍 成年人。这一框架将为制定秋季精准医疗战略提供基础。 预防，特别是在阿尔茨海默病和随后跌倒的高危人群中。

PROJECT SUMMARY/ABSTRACT During the aging process there is a loss of automaticity in balance and mobility, where the engagement of cortical resources for balance control may interfere with older adults’ ability to perform cognitive and balance behaviors simultaneously. Over the course of normal aging, there is a decline in cerebral blood flow that is linked to impaired cognitive function in older adults. However, it remains unknown whether age-related declines in cerebrovascular and nervous system function may interact to manifest as cognitive interference in balance control that precipitate falls and clinical dementia. Further, older adults who carry the Apolipoprotein E4 (APOE4) allele, the greatest known genetic risk factor for Alzheimer’s disease, show greater cerebrovascular dysfunction compared to age-matched noncarriers, and display worse balance performance under cognitive loading conditions, supporting the potential effect of individual genotype on the link between cerebrovascular health and balance control with aging. Using electroencephalography (EEG) to measure dynamic cortical activity during standing balance reactions, the candidate’s recent fellowship findings provide an individualized framework of cortical engagement strategies for balance control in older adults that is associated with distinct aspects of balance behavior and fall risk, including cognitive interference in balance performance. Currently, a major scientific barrier to the clinical translation of this research is the lack of understanding of the factors that influence individual-specific cortical strategies for balance control with aging. Emerging evidence suggests cognitive impairment with aging may be caused by dysfunctional cerebral blood flow, specifically characterized by impaired cerebrovascular regulation under conditions of physiologic stress. Blunted cerebral blood flow response to an acute bout aerobic exercise, an assessment method pioneered by Dr. Billinger (primary mentor) and her laboratory, appears to be an early indicator of dysfunctional cerebrovascular regulation in preclinical older adult populations. The proposed project will be the first to test the link between cerebrovascular regulation during an acute bout of aerobic exercise, measured as cerebral blood flow velocity using transcranial Doppler ultrasound, and cortical function during balance behavior with aging, measured with cognitive dual-task balance performance (Aim 1) and EEG measures of cortical activity during balance reactions (Aim 2). An Exploratory Aim will test whether genetic APOE4 carrier status alters the relationship between cerebrovascular regulation and balance control in older adults. The scientific knowledge gained from these studies would create an individualized framework for understanding cardiovascular-nervous system interactions that may contribute to balance disability in older adults. This framework would provide a foundation for the development of precision-medicine strategies for fall prevention, particularly in individuals at high risk for Alzheimer’s disease and subsequent falls.