Vascular mechanisms and tDCS treatment of gait and posture in aging and age-related disease

衰老和年龄相关疾病中步态和姿势的血管机制和 tDCS 治疗

• 批准号: 9243599
• 负责人: Azizah J. Jor'dan
• 金额: $ 0.33万
• 依托单位: HEBREW REHABILITATION CENTER FOR AGED
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-15 至 2017-03-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9243599
• 关键词: Acute; Adult; Aging; Alzheimer' s Disease; Blood; Blood Flow Velocity; Blood Vessels; Blood flow; Brain; Cerebrovascular Circulation; Clinical; Cognition; Cognitive; Complex; Diabetes Mellitus; Disease; Doppler Ultrasound; Education; Elderly; Electrical Stimulation of the Brain; Electrodes; Equilibrium; Exhibits; Future; Gait; Gait speed; Goals; Hand; Impairment; Intervention; Learning; Left; Link; Magnetic Resonance Imaging; Measures; Methods; Motor; Musculoskeletal Equilibrium; Near-Infrared Spectroscopy; Neurons; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Oxygen; Patients; Phase; Population; Posture; Prefrontal Cortex; Process; Quality of life; Randomized; Recruitment Activity; Rehabilitation therapy; Research; Research Personnel; Scalp structure; Scientist; Speed; Task Performances; Techniques; Technology; Time Study; Translating; Vascular resistance; Visit; Vulnerable Populations; Walking; Work; age effect; age related; career; cerebrovascular; cost; design; equilibration disorder; follow-up; functional improvement; functional outcomes; group intervention; improved; improved mobility; insight; middle cerebral artery; neuroimaging; neuronal excitability; neurophysiology; neuroregulation; new therapeutic target; relating to nervous system; screening; skills; tool; translational research program; young adult

PROPOSAL SUMMARY My career goal is to become a leading academic scientist with a research focus on the neurophysiology of balance disorders in aging and age-related disease. I will achieve this goal by leading a translational research program aimed at identifying the pathophysiological manifestations of aging and age-related disease that diminish the control of walking and standing, and their consequences on important clinical outcomes such as mobility. I will also work to translate these discoveries into future clinical interventions and practices that will improve mobility and quality of life within these populations. The control of gait and posture is dependent upon cognition and is linked to prefrontal brain function in healthy adults. The proposed K99 phase research has been designed to, for the first time, study the effects of aging, type 2 diabetes mellitus (DM) and Alzheimer’s disease (AD) on prefrontal brain activation during standing and walking. Both DM and AD exaggerate age-related declines in gait and posture, and it is expected that this is caused at least in part by shared cerebrovascular complications; namely, a reduced ability to sufficiently activate the prefrontal cortex during these activities due to decrease blood flow and increased vascular resistance. With this information in hand, the proposed R00 phase research will then attempt to increase prefrontal brain activation using transcranial direct current stimulation (tDCS) in order to improve walking and standing in these patients. Thus, the following Specific Aims will be completed: K99 Aim 1 will determine, cross-sectionally, the relationship between gait and postural control and markers of brain activation during these activities in younger and older adults, as well as older adults with DM or AD. Brain activation markers (i.e., blood flow, blood oxygenation) will be quantified using transcranial Doppler ultrasound and functional near-infrared spectroscopy. We hypothesize that H1) those who exhibit slower gait speed when walking and greater postural sway speed when standing will exhibit less brain activation during these tasks and H2) brain activation during gait and postural control will be greatest in healthy young, lower in healthy old, and lowest in the disease groups. R00 Aim 2 will determine, using a 10-day tDCS intervention, a) the effects of tDCS targeting the prefrontal cortex on gait and postural control and brain activation, and b) the immediate and longer-term (i.e., over a one- month follow-up) effects on these outcomes in patients with DM or AD. Those who exhibit gait and postural control difficulties at baseline will be randomized into real or sham (i.e., control) tDCS intervention groups. We hypothesize that H3) the real tDCS group will exhibit an increase in gait speed when walking and reduction of postural sway speed when standing, and an increase in brain activation during these tasks, both immediately and over the 30-day follow-up period. Together, these discoveries will provide insight into the cerebrovascular control of gait and postural control in aging and age-related disease; and new therapeutic targets (i.e., blood flow and blood oxygenation) for balance rehabilitation. Moreover, it will identify tDCS as an important tool in balance research that may translate into a new low-cost and safe intervention for these vulnerable populations.

建议书摘要 我的职业目标是成为一名领先的学术科学家，专注于神经生理学的研究 衰老和老年性疾病中的平衡障碍。我将通过领导一个翻译研究来实现这一目标 旨在确定老龄化和与年龄相关的疾病的病理生理表现的计划， 减少对行走和站立的控制及其对重要临床结果的影响，例如 机动性。我还将努力将这些发现转化为未来的临床干预和实践， 改善这些人口的流动性和生活质量。 步态和姿势的控制依赖于认知，并与健康人的前额叶脑功能有关 成年人。拟议的K99阶段研究旨在首次研究老化的影响， 2型糖尿病(DM)和阿尔茨海默病(AD)对站立和站立时前额叶脑激活的影响 走路。DM和AD都夸大了与年龄相关的步态和姿势的下降，预计这是 至少部分是由共同的脑血管并发症引起的；即，充分 在这些活动中，由于血流量减少和血管增加，激活前额叶皮质 抵抗。有了这些信息，拟议的R00阶段研究将尝试增加 利用经颅直流电刺激(Tdcs)激活前额脑以改善步行和运动能力。 站在这些病人中间。因此，将完成以下具体目标： K99目标1将横断面确定步态和姿势控制之间的关系以及 年轻人和老年人以及患有糖尿病或AD的老年人在这些活动期间的大脑激活。脑区 激活标记物(即血流、血氧)将使用经颅多普勒超声进行量化 和功能性近红外光谱分析。我们假设H1)那些步态速度较慢的人在 在这些任务中，走路和站立时较大的姿势摆动速度会显示出较少的大脑激活 H2)在步态和姿势控制过程中，健康年轻人的大脑活动最大，健康老年人的大脑活动较低，以及 在疾病组中最低。 R00目标2将使用为期10天的tdcs干预来确定a)tdcs针对前额叶的影响 大脑皮层对步态和姿势的控制以及大脑的激活，以及b)即刻和较长期的(即，超过一 一个月的随访)对糖尿病或AD患者的这些结果的影响。那些表现出步态和姿势的人 基线控制困难将随机分为真实或假(即对照)tdcs干预组。我们 假设H3)真实的tdcs组将表现出行走时步速的增加和 站立时的姿势摆动速度，以及在这些任务中大脑激活的增加，都是立即发生的 并在30天的随访期内完成。 总之，这些发现将为脑血管控制步态和姿势控制提供洞察力。 老龄化和与年龄相关的疾病；以及新的治疗目标(即血流和血氧) 恢复平衡。此外，它将确定tdcs是平衡研究的重要工具，可以 为这些弱势群体提供一种新的低成本、安全的干预措施。