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

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: 10413934
• 负责人: Azizah J. Jor'dan
• 金额: $ 24.23万
• 依托单位: UNIVERSITY OF MASSACHUSETTS BOSTON
• 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 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10413934
• 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; Education; Elderly; Electrical Stimulation of the Brain; Electrodes; Equilibrium; Exhibits; Future; Gait; Gait speed; Goals; Hand; Intervention; Learning; Left; Link; Magnetic Resonance Imaging; Measures; Methods; Motor; Musculoskeletal Equilibrium; Nerve Degeneration; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Oxygen; Patients; Phase; Population; Posture; Prefrontal Cortex; Process; Quality of life; Randomized; Rehabilitation therapy; Research; Research Personnel; Scalp structure; Scientist; Speed; Task Performances; Techniques; Technology; Time Study; Transcranial Doppler Ultrasonography; Translating; Vascular resistance; Visit; Vulnerable Populations; Walking; Work; age effect; age related; brain dysfunction; career; cerebrovascular; cost; design; equilibration disorder; follow-up; functional improvement; functional near infrared spectroscopy; functional outcomes; group intervention; improved; improved mobility; insight; middle cerebral artery; neuroimaging; neuronal excitability; neurophysiology; neuroregulation; new therapeutic target; placebo group; recruit; rehabilitation strategy; relating to nervous system; screening; skills; tool; translational research program; wireless sensor; young adult

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 manifestation 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 K99 phase research was 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 R00 Specific Aim will be completed: R00 Aim 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 markers (i.e., blood flow, blood oxygenation), 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 H1) 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.

我的职业目标是成为一名领先的学术科学家，研究重点是 神经生理学的平衡障碍在老龄化和年龄相关疾病。我将通过以下方式实现这一目标： 领导一个转化研究计划，旨在确定病理生理表现， 衰老和与年龄有关的疾病，减少了对行走和站立的控制， 对重要临床结局（如活动性）的影响。我也会努力翻译 将这些发现转化为未来的临床干预和实践， 这些人群的流动性和生活质量。 步态和姿势的控制依赖于认知，并与前额叶脑有关 在健康成年人中发挥作用。K99阶段研究旨在首次研究 增龄、2型糖尿病和阿尔茨海默病对前额叶脑的影响 在站立和行走时激活。DM和AD都夸大了与年龄相关的步态下降， 姿势，预计这至少部分是由共享脑血管引起的 并发症;也就是说，在治疗过程中充分激活前额叶皮层的能力降低。 这些活动是由于血流减少和血管阻力增加。与此 根据现有信息，建议的R00阶段研究将尝试增加 使用经颅直流电刺激（tDCS）激活前额脑， 改善这些患者的行走和站立。因此，以下R00具体目标将是 已完成： R00 Aim将使用10天的tDCS干预来确定：a）tDCS针对 前额叶皮层对步态和姿势控制以及大脑激活标记（即，血液 流量，血氧），和B）即时和长期（即，一个多月 随访）对DM或AD患者的这些结局的影响。那些表现出步态和姿势 基线时的控制困难将被随机分为真实的或假的（即，控制）tDCS 干预组。我们假设H1）真实的tDCS组将表现出步态的增加 步行时的速度和站立时姿势摆动速度的减少，以及大脑中 在这些任务期间立即和30天随访期间激活。 总之，这些发现将为步态的脑血管控制提供深入了解， 衰老和年龄相关疾病中的姿势控制;以及新的治疗靶点（即，血流 和血液氧合）用于平衡恢复。此外，它将确定tDCS是一个重要的 这是一个平衡研究的工具，可以转化为对这些弱势群体的新的低成本和安全的干预措施。

项目成果

Transcranial Direct Current Stimulation May Reduce Prefrontal Recruitment During Dual Task Walking in Functionally Limited Older Adults - A Pilot Study.

• DOI: 10.3389/fnagi.2022.843122
• 发表时间: 2022
• 期刊: Frontiers in aging neuroscience
• 影响因子: 4.8
• 作者: Jor'dan AJ;Bernad-Elazari H;Mirelman A;Gouskova NA;Lo OY;Hausdorff JM;Manor B
• 通讯作者: Manor B

Neuromuscular Attributes are Associated with Poor Mobility in Older Adults with Vascular Risk Conditions.

• DOI: 10.14283/jfa.2019.42
• 发表时间: 2020
• 期刊: The Journal of frailty & aging
• 作者: Jor'dan AJ;Jacob ME;Leritz E;Bean JF
• 通讯作者: Bean JF