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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

基本信息

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
项目类别：
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&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease diagnosis Alzheimer&apos s disease pathology Alzheimer&apos 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

项目摘要

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.

项目总结