Effects of Resonance-Frequency Breathing on Preclinical Alzheimer’s Disease Biomarkers and Cognition

共振频率呼吸对临床前阿尔茨海默病生物标志物和认知的影响

• 批准号: 10591329
• 负责人: MARA MATHER
• 金额: $ 78.85万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-15 至 2028-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10591329
• 关键词: Abeta synthesis; Acceleration; Adrenergic Agents; Adult; Affect; African American; African American population; Age; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease diagnosis; Alzheimer' s disease pathology; Alzheimer' s disease risk; Alzheimer’s disease biomarker; American; Amyloid; Amyloid beta-42; Amyloid beta-Protein; Amyloid deposition; Amyloidosis; Baroreflex; Biofeedback; Biological Markers; Blood; Blood Vessels; Brain; Brain Injuries; Breathing; Clinical Trials; Cognition; Cognitive; Discrimination; Disease; Double-Blind Method; Drug Targeting; Early Intervention; Elderly; Ethnic Origin; European; Foundations; Frequencies; Future; Genetic Transcription; Heart Rate; Hippocampus; Impaired cognition; Impairment; Influentials; Intervention; Learning; Measures; Mediating; Modeling; Neocortex; Neurobiology; Outcome; Participant; Pathologic; Pathologic Processes; Pathway interactions; Patients; Perception; Performance; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Plasma; Play; Production; Protein Fragment; Proteins; Randomized; Reporting; Research; Risk; Signal Transduction; Synaptic plasticity; System; Testing; Training; Vagus nerve structure; active control; active control group; aged; arm; cerebrospinal fluid flow; cognitive task; cohort; ethnic difference; glymphatic clearance; glymphatic system; heart rate variability; improved; innovation; intervention cost; intervention effect; middle age; neocortical; noradrenergic; personalized strategies; post intervention; pre-clinical; prevent; randomized trial; recruit; sex; side effect; success; tau Proteins; wasting; young adult

PROJECT SUMMARY The cascade of pathological changes involved in Alzheimer’s disease (AD) starts many years before AD diagnosis, suggesting that intervening with still-healthy adults will be most successful. According to the influential amyloid hypothesis, an imbalance between β-amyloid (Αβ) production and clearance initiates changes that lead to AD. This hypothesis suggests that early intervention targeting Αβ levels should be particularly effective in preventing AD, but the field has yet to test this core prediction of the hypothesis. A major obstacle is the lack of safe and low-cost interventions that reduce Αβ. Initial findings (N = 108) from our recently completed heart rate variability (HRV) biofeedback clinical trial indicate that daily sessions attempting to increase (via resonance-frequency breathing) vs. decrease (via personalized strategies) heart rate oscillations have significant opposing outcomes on plasma Αβ levels. Resonance-frequency breathing reduced overall plasma Αβ levels in both younger and older adults, and, among adults aged 55-70, increased Αβ42/Αβ40 ratios, a biomarker of reduced amyloid deposition in the brain. In this stage II double-blinded randomized trial, we aim to test hypotheses regarding the mechanisms behind this result as well as cognitive outcomes in African-American and European-American adults aged 50-70. Participants will complete ten weeks of daily paced breathing sessions, randomized to either a resonance-frequency breathing or a random- paced breathing condition. We hypothesize that resonance-frequency breathing reduces plasma biomarkers of AD risk via two synergistic pathways: 1) afferent vagus nerve activity suppresses noradrenergic activity that stimulates Aβ production; and 2) heart rate oscillations increase cerebrospinal fluid (CSF) flow, increasing brain clearance of Aβ42 in adults in their 50’s and 60’s in whom glymphatic clearance is declining. We will model how pre/post intervention change in plasma AD biomarkers relates to biomarkers associated with each of these hypothesized pathways. Compared with European Americans, African Americans have higher AD risk and higher noradrenergic/sympathetic system activity. They therefore may particularly benefit from resonance- frequency breathing. Across ethnicities, reduced levels of Αβ should especially benefit adults in their 50’s and 60’s, in whom amyloid is starting to aggregate in the brain as glymphatic clearance becomes less effective. The initial aggregative Αβ form (oligomeric Αβ) interferes with synaptic plasticity, so we will assess how much participants in the two conditions improve their performance on cognitive tasks they practice daily for 10 weeks. This innovative project will serve as a foundation for future long-term clinical trials to test the potential of resonance-frequency breathing to slow cognitive decline and prevent AD by reducing Αβ.

项目摘要 阿尔茨海默氏病（AD）涉及的一系列病理变化（AD）开始了多年 诊断，表明与仍然健康的成年人进行干预是最成功的。根据 有影响力的淀粉样假说，β-淀粉样蛋白（αβ）的产生与清除率的失衡 导致广告的变化。该假设表明，针对αβ水平的早期干预应为 在防止AD方面特别有效，但该领域尚未检验该假设的核心预测。一个 主要障碍是缺乏减少αβ的安全和低成本干预措施。我们的初始发现（n = 108） 最近完成的心率变异性（HRV）生物反馈临床试验指标 增加（通过共振频率呼吸）与（通过个性化策略）心率下降 振荡在等离子体αβ水平上具有显着的相反结果。共振频率呼吸减少 年轻人和老年人的总体血浆αβ水平，在55-70岁的成年人中， Aβ42/Aβ40比，这是大脑中淀粉样蛋白沉积减少的生物标志物。在这个阶段II双盲 随机试验，我们旨在检验有关该结果背后机制和认知机制的假设 50-70岁的非裔美国人和欧美成年人的成果。参与者将完成十个 每天的几周节奏呼吸，随机分配给共振频率呼吸或随机 - 节奏的呼吸条件。我们假设共振频率呼吸减少了血浆生物标志物 通过两种协同途径的AD风险：1）传入迷走神经活动抑制甲肾上腺素能活性 刺激Aβ产生； 2）心率振荡会增加脑脊液（CSF）的流量，增加 在50年代和60年代成年人的大脑清除，在他们的50年代和60年代的大脑清除率正在下降。我们将 模拟与每种相关的生物标志物相关的血浆AD生物标志物的干预前/后干预变化 这些假设的途径。与欧洲人相比，非裔美国人的广告风险更高 以及更高的去甲肾上腺素能/交感神经系统活性。因此，它们可能特别受益于共鸣 - 呼吸频率。在整个种族中，Aβ水平的降低应特别受益于成年人的50年代，并且 60年代，由于淀粉样蛋白的效果降低，淀粉样蛋白开始在大脑中聚集。 初始聚集αβ形式（寡聚αβ）干扰了合成可塑性，因此我们将评估多少 在这两个条件下的参与者提高了他们每天练习10的认知任务的表现 几周。这个创新的项目将成为未来长期临床试验的基础，以测试潜力 共振 - 频率呼吸以减慢认知能力下降并通过减少Aβ来防止AD。