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.

项目概要/摘要 在衰老过程中，平衡和活动能力会丧失，其中 用于平衡控制的皮层资源可能会干扰老年人的认知和平衡能力 同时行为。在正常衰老过程中，脑血流量会下降 与老年人认知功能受损有关。但目前尚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，表现为认知干扰 平衡控制会导致跌倒和临床痴呆。此外，携带载脂蛋白的老年人 E4 (APOE4) 等位基因是已知的阿尔茨海默病最大的遗传风险因素，显示出更大的 与年龄匹配的非携带者相比，存在脑血管功能障碍，并且平衡能力较差 在认知负荷条件下，支持个体基因型对之间联系的潜在影响 脑血管健康和衰老的平衡控制。 使用脑电图（EEG）测量站立平衡反应期间的动态皮层活动， 候选人最近的奖学金发现提供了皮质参与的个性化框架 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，包括平衡表现中的认知干扰。目前，临床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理解 平衡控制与衰老的策略。新的证据表明，随着年龄的增长，认知功能障碍可能是 由脑血流功能失调引起，特别是脑血管调节受损 在生理应激条件下。对急性有氧运动的脑血流反应减弱， Billinger 博士（主要导师）和她的实验室首创的一种评估方法，似乎是一种早期的评估方法。 临床前老年人群脑血管调节功能失调的指标。拟议的 该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 运动，使用经颅多普勒超声测量脑血流速度，以及皮质 平衡行为与衰老过程中的功能，通过认知双任务平衡表现来测量（目标 1) 平衡反应期间皮层活动的脑电图测量（目标 2）。探索性目标将测试是否 遗传性 APOE4 携带状态改变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 了解可能有助于老年人平衡障碍的心血管-神经系统相互作用 成年人。该框架将为制定秋季精准医疗策略奠定基础 预防，特别是对于患有阿尔茨海默病和随后跌倒的高风险人群。