Cognitively engaging walking exercise and neuromodulation to enhance brain function in older adults

认知性步行锻炼和神经调节可增强老年人的大脑功能

• 批准号: 10635832
• 负责人: David J Clark
• 金额: $ 124.5万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10635832
• 关键词: Adjuvant; Aerobic; Affect; Age; Age-associated memory impairment; Alzheimer' s Disease; Alzheimer' s disease related dementia; Behavior Therapy; Behavioral; Brain; Brain region; Cathodes; Clinical; Cognition; Cognitive; Cognitive aging; Complex; Control Groups; Elderly; Electric Stimulation; Electrical Stimulation of the Brain; Enrollment; Esthesia; Exercise; Intervention; Knowledge; Magnetic Resonance Imaging; Measures; Mediation; Membrane Potentials; Modeling; Motor; Neuronal Plasticity; Neurons; Outcome; Participant; Patient Self-Report; Performance; Persons; Pilot Projects; Prefrontal Cortex; Procedures; Randomized; Research; Research Infrastructure; Risk Factors; Role; Safety; Site; Surface; Targeted Research; Testing; Therapeutic; United States National Institutes of Health; Walking; behavioral outcome; cognitive function; cognitive task; cohort; combinatorial; density; design; dosage; efficacy evaluation; executive function; experience; falls; frontal lobe; functional near infrared spectroscopy; functional restoration; improved; machine learning algorithm; multi-component intervention; neuroregulation; phase 1 study; phase 2 study; placebo group; preservation; prevent; recruit; response; supervised learning; transcranial direct current stimulation; treatment group; walking program; walking speed

Declines in cognitive function and walking function are highly intertwined in older adults. For instance, lower executive function exacerbates conversion to Alzheimer’s disease and is also associated with slow walking speed, instability, and falling. In turn, low levels of walking activity are a risk factor for age-related cognitive decline including Alzheimer’s disease. Combinatorial interventions that target both cognition and walking function may break this vicious cycle. Prefrontal networks are a crucial intervention target due to their role in executive function, which underlies performance of both complex cognitive tasks and complex walking tasks. Our research targets prefrontal neuroplasticity using a potent behavioral intervention of complex (cognitively engaging) aerobic walking exercise combined with frontal lobe transcranial direct current stimulation (tDCS). tDCS is a mild form of electrical brain stimulation which may be an effective adjuvant for enhancing the effects of behavioral interventions on cognitive and motor function. The overarching hypothesis of our research is that tDCS delivered over prefrontal regions during complex walking exercise can improve both executive function and walking function. We have previously conducted a successful Phase 1 study that demonstrated feasibility, safety, and positive behavioral outcomes from this intervention in older adults. Now we are proposing a Phase 2 study that is designed to establish initial efficacy, investigate mechanisms of intervention response, and to develop a multi-site research infrastructure. We will enroll 104 older adult participants who have age-related cognitive decline. All participants will undergo the same 18-session high intensity aerobic walking program, which will emphasize the use of complex walking tasks that engage prefrontal cortex, such as obstacle negotiation and walking on compliant surfaces. Participants will be randomly assigned to a tDCS treatment group or sham control group. The treatment group will receive 20 minutes of 2mA tDCS over prefrontal regions F3/F4. The sham control group will receive just 30 seconds of 2mA tDCS at F3/F4 at the beginning of the session, which is known to be an effective sham procedure. A wearable stimulator will be used, so participants can receive stimulation while simultaneously performing the complex walking exercise. Specific Aim 1 will establish efficacy of prefrontal tDCS as an adjuvant to complex walking exercise for enhancing executive function and walking function. Specific Aim 2 will investigate mechanisms of response, including task-based prefrontal activity (with functional near infrared spectroscopy), MRI modeling of person-specific tDCS dosage, and their association with behavioral outcomes. The deliverable for this line of research will be a clinically- feasible multi-modal intervention for preserving function and independence in older adults.

老年人的认知功能和步行功能的下降是紧密相关的。 执行功能会恶化阿尔茨海默氏病的转化，并且还与缓慢行走有关 反过来，低水平的步行活动是与年龄相关的认知的危险因素。 针对认知和步行的组合干预措施。 前额叶网络由于其在其中的作用而成为重要的干预目标。 执行功能，是执行复杂认知任务和复杂行走任务的基础。 我们的研究针对前额神经可塑性，使用复杂的有效行为干预（认知 参与）有氧步行运动结合额叶经颅直流电刺激（tDCS）。 tDCS 是一种温和的脑电刺激形式，可能是增强效果的有效佐剂 我们研究的总体假设是： 在复杂的步行锻炼过程中，在前额叶区域进行经颅直流电刺激 (tDCS) 可以改善执行功能 我们之前进行了一项成功的第一阶段研究，证明了可行性， 这种干预对老年人的安全性和积极的行为结果现在我们提出一个阶段。 2 研究旨在确定初步疗效、调查干预反应机制并 我们将招募 104 名与年龄相关的老年人参与者。 所有参与者都将接受相同的 18 节高强度有氧步行计划， 这将强调使用涉及前额皮质的复杂步行任务，例如障碍 参与者将被随机分配接受 tDCS 治疗。 治疗组或假对照组将在前额叶区域接受 20 分钟的 2mA tDCS。 F3/F4。假对照组将在 F3/F4 开始时仅接收 30 秒的 2mA tDCS。 会议，这被认为是一种有效的假手术，将使用可穿戴刺激器，因此参与者。 可以在进行复杂的步行练习的同时接受刺激。 确定前额叶 tDCS 作为复杂步行运动的辅助手段以增强执行力的功效 具体目标 2 将研究反应机制，包括基于任务的反应机制。 前额叶活动（具有功能性近红外光谱）、个人特定 tDCS 剂量的 MRI 模型、 以及它们与行为结果的关联。这一系列研究的成果将是临床- 可行的多模式干预，以保护老年人的功能和独立性。