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.

在老年人中，认知功能和步行功能的下降高度交织在一起。例如，较低 执行功能加剧了转换为阿尔茨海默氏病，也与步行缓慢有关 速度，不稳定和下降。反过来，步行水平较低是与年龄相关的认知的危险因素 包括阿尔茨海默氏病在内的下降。针对认知和步行的组合干预措施 功能可能会打破这个恶性循环。前额叶网络是至关重要的干预目标，因为它们在 执行功能，这是复杂的认知任务和复杂步行任务的绩效的基础。 我们的研究使用复杂的潜在行为干预（认知上 参与）有氧步行锻炼与额叶trancranial直流刺激（TDCS）结合使用。 TDC是一种轻度的电脑刺激形式，可能是有效的调整以增强效果 对认知和运动功能的行为干预措施。我们研究的总体假设是 复杂步行练习期间，在前额叶区域交付的TDC可以改善两种执行功能 和步行功能。我们以前已经进行了一项成功的1期研究，该研究证明了可行性， 这项干预措施的安全性和阳性行为结果。现在我们提出了一个阶段 2研究旨在建立初始效率，研究干预响应的机制以及 开发多站点的研究基础架构。我们将注册104名与年龄相关的老年人 认知能力下降。所有参与者将接受相同的18条经验高强度有氧步行计划， 这将强调使用具有前额叶皮层的复杂行走任务，例如障碍物 谈判和在合规表面上行走。参与者将被随机分配到TDCS治疗 组或假对照组。该治疗组将在前额叶区域接收20分钟的2MA TDC F3/F4。假对照组将在F3/f4开始时仅获得30秒的2MA TDC 会议，这是一个有效的假程序。将使用可穿戴刺激器，因此参与者 可以同时进行复杂的步行练习，同时接受刺激。具体目标1将 建立前额叶TDC的有效性，以调节复杂的步行练习，以增强执行官 功能和步行功能。具体目标2将研究响应的机制，包括基于任务 前额叶活性（具有功能性近红外光谱法），人为特异性TDC剂量的MRI模型， 以及他们与行为结果的联系。这项研究方面的交付将是临床上的 可行的多模式干预措施，以保存老年人的功能和独立性。