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

研究运动期间的脑血管调节作为影响皮质资源参与以控制衰老平衡的因素

• 批准号: 10704499
• 负责人: Jacqueline A Palmer
• 金额: $ 11.53万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10704499
• 关键词: Acute; Adult; Aerobic Exercise; Age; Aging; Alleles; Alzheimer' s Disease; Alzheimer' s disease risk; Attenuated; Behavior; Blood Flow Velocity; Blood flow; Brain; Cardiovascular system; Career Choice; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrovascular system; Clinical; Cognitive; Dementia; Development; Early Diagnosis; Elderly; Electroencephalography; Equilibrium; Exercise; Fall prevention; Fellowship; Foundations; Genetic; Genotype; Goals; Impaired cognition; Impaired health; Impairment; Individual; Knowledge; Laboratories; Link; Longevity; Maintenance; Measures; Mediating; Mentors; Methods; Motor; Nervous System; Nervous System Physiology; Performance; Physical activity; Physical therapy; Physiological; Population; Positioning Attribute; Prevention; Process; Reaction; Regulation; Research Training; Resources; Rest; Science; Stress; Task Performances; Testing; Training; Transcranial Doppler Ultrasonography; Translational Research; Walking; age related; aging brain; apolipoprotein E-4; brain dysfunction; brain health; carrier status; cerebrovascular; cerebrovascular health; clinical training; clinical translation; cognitive function; cognitive load; daily functioning; design; disability; early onset; executive function; fall risk; falls; genetic risk factor; high risk; human old age (65+); innovation; insight; middle age; multimodality; neuropathology; neurophysiology; neuroprotection; normal aging; post stroke; pre-clinical; precision medicine; preservation; response; skills

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.

项目摘要/摘要 在衰老过程中，平衡和流动性的自动化丧失，参与 平衡控制的皮质资源可能会干扰老年人的认知能力和平衡 行为很简单。在正常衰老的过程中，脑血流有所下降 与老年人认知功能受损有关。但是，尚不清楚是否与年龄有关 脑血管和神经系统功能的下降可能相互作用，表现为认知干扰 平衡珍贵跌倒和临床痴呆症的控制。此外，携带载脂蛋白的老年人 E4（APOE4）等位基因是阿尔茨海默氏病的最大已知遗传危险因素，显示出更大的 与年龄匹配的非驾驶员相比，脑血管功能障碍和表现较差 在认知载荷条件下，支持各个基因型对之间的潜在影响 脑血管健康和平衡控制随老化的状态。 使用脑电图（EEG）测量常规平衡反应期间的动态皮质活性， 候选人最近的奖学金结果提供了一个个性化的皮质参与框架 老年人平衡控制的策略与平衡行为的不同方面相关并下降 风险，包括对平衡表现的认知干扰。目前，临床的主要科学障碍 这项研究的翻译是对影响个体特异性皮质的因素缺乏了解 衰老的平衡控制策略。新兴证据表明，衰老的认知障碍可能是 由功能失调的脑血流量引起的，特别是由脑血管调节受损的特征 在生理压力的条件下。对急性回合有氧运动的脑血流反应钝化 Billinger博士（主要导师）及其实验室率先进行的评估方法似乎是早期的 临床前老年人群中脑血管调节功能失调的指标。提议 项目将是第一个测试急性有氧运动期间脑血管调节之间联系的项目 锻炼，使用trancranial多普勒超声和皮质测量为脑血流速度 通过认知双任务余额表现衡量的平衡行为的功能（目标） 1）在平衡反应过程中皮质活性的脑电图测量（AIM 2）。探索目的将测试是否 遗传APOE4载体状态改变了脑血管调节与平衡控制之间的关系 老年人。从这些研究中获得的科学知识将为 了解可能导致较老的残疾平衡的心血管造成系统相互作用 成年人。该框架将为制定秋季精密中等医学策略提供基础 预防，特别是在患阿尔茨海默氏病高风险的个体中，随后跌倒。