Personalized Synchronization of Cortical Rhythms to Improve Memory in Alzheimer's Disease

皮质节律的个性化同步可改善阿尔茨海默氏病的记忆力

基本信息

批准号：
10709218
负责人：
Robert Reinhart
金额：
$ 41.25万
依托单位：
BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
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：
2023-09-01 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10709218
关键词：
Activities of Daily Living Affect Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease patient Alzheimer&apos s disease related dementia Area Behavioral Brain Brain Diseases Cephalic Code Cognition Cognitive Cognitive deficits Cortical Synchronization Coupled Coupling Data Data Collection Dementia Deterioration Development Disease Double-Blind Method Economics Electroencephalography Electrophysiology (science)Ensure Frequencies Functional disorder Future Goals Health Care Costs Human Impairment Individual Individual Differences Intervention Investigation Knowledge Maintenance Measurement Measures Mediating Memory Memory impairment Methods Nature Network-based Neurosciences Pattern Performance Periodicity Persons Phase Physiological Population Prefrontal Cortex Procedures Protocols documentation Public Health Quality of life Randomized Reproducibility of Results Research Research Personnel Sample Size Scheme Short-Term Memory Social Functioning Source Specificity Syndrome System Techniques Temporal Lobe Testing Therapeutic Therapeutic Intervention Validity of Results cognitive function cost cost estimate density disability drug development executive function experimental study flexibility functional disability improved indexing interest long term memory mild cognitive impairment neural neuromechanism neurophysiology neuroregulation novel novel therapeutics pathological aging power analysis programs reconstruction segregation social statistics support network theories tool translational neuroscience translational progress

项目摘要

PROJECT SUMMARY/ABSTRACT Alzheimer’s disease is a severely debilitating disorder. It affects over 50 million people worldwide and its associated costs are estimated to exceed $305 billion annually. By mid-century, 153 million people are expected to be living with Alzheimer’s disease and costs are projected to surpass $1 trillion, as the global population rapidly ages. Impaired working memory is a central feature of the cognitive deterioration in Alzheimer’s disease and a primary driver of disability, placing sharp limits on social functioning, activities of daily living, and quality of life. Working memory refers to our ability to hold behaviorally useful information in mind over a period of seconds and is a fundamental building block of human cognition and the gateway to long-term memory. Neuroscience investigations have demonstrated that working memory function is subserved by oscillatory mechanisms in the healthy brain, and that specific patterns of synchronous oscillatory dynamics may be important for understanding the disease mechanisms of Alzheimer’s disease, consistent with the longstanding hypothesis of Alzheimer’s disease as a disconnection syndrome. Here, we examine the mechanisms of working memory impairment in Alzheimer’s disease from a physiologically inspired perspective centered on large-scale brain networks and how they interact through synchronized electrophysiological oscillations. We focus on established neural coding schemes (i.e., cross-frequency coupling and phase synchronization) hypothesized to index flexible large-scale circuits that integrate information across multiple temporal and spatial scales during cognition. We combine high-density electroencephalographic measurements of synchronized oscillations with personalized high-definition transcranial alternating-current stimulation to determine whether it is possible to modify components of frontotemporal networks and cause rapid improvements in working memory function. Our preliminary data are highly encouraging and indicate that we can causally modulate the synchronization of long-range low-frequency oscillations, increase local phase- amplitude coupling, and improve working memory capacity in people with Alzheimer’s disease to levels equivalent to that of demographically matched healthy controls. The goals of the research program are to use novel neuroscience tools and analytic procedures to gain a deeper understanding of the pathophysiology of memory impairment in Alzheimer’s disease, and achieve concrete translational progress toward the development of personalized, non-pharmacological interventions for improving memory and cognition in Alzheimer’s disease and related dementias.

项目摘要/摘要阿尔茨海默氏病是一种严重的使人衰弱的疾病。它影响了全球超过5000万人及其相关费用估计每年超过300亿美元。到本世纪中叶，有1.53亿人已经预计将患有阿尔茨海默氏病，费用预计将超过1万亿美元，因为全球人口迅速年龄。工作记忆受损是认知定义的核心特征阿尔茨海默氏病和残疾的主要驱动力，对社会功能施加了急剧的限制，日常生活和生活质量。工作记忆是指我们在行为上有用信息的能力在几秒钟内的思想，是人类认知的基本组成部分，也是通往的门户长期记忆。神经科学的调查表明，工作记忆功能是通过健康大脑中的振荡机制以及同步振荡的特定模式提供的费用动力学对于理解阿尔茨海默氏病的疾病机制可能很重要，与长期以来，阿尔茨海默氏病是断裂综合征。在这里，我们检查了从身体启发的角度来看，阿尔茨海默氏病的工作记忆障碍机制集中在大型大脑网络以及它们如何通过同步电生理学相互作用振荡。我们专注于既定的神经编码方案（即跨频耦合和相位同步）假设索引索引柔性大规模电路，这些电路将信息整合到多个认知过程中的临时和空间尺度。我们结合了高密度脑电图用个性化的高清经颅替代流对同步振荡的测量刺激以确定是否可以修改额颞网络的组件并导致快速改善工作记忆功能。我们的初步数据令人鼓舞，并表明我们可以为远距离低频振荡的同步来调节，增加局部相 - 振幅耦合，并将阿尔茨海默氏病患者的工作记忆能力提高到水平相当于人口统计学匹配的健康对照。研究计划的目标是使用新颖的神经科学工具和分析程序，以更深入地了解阿尔茨海默氏病的记忆障碍，并取得了具体的转化进度开发个性化的非药理学干预措施，以改善记忆和认知阿尔茨海默氏病和相关痴呆症。