Neurobiological mechanisms of sleep and exercise effects on memory in older adults at risk for Alzheimer's disease

项目总结 阿尔茨海默病是一种进行性痴呆症，没有有效的治疗方法。情景记忆缺陷 是阿尔茨海默病的一个明显的认知症状，这可能与内侧颞叶的变化有关 叶数(MTL)。MTL促进情景记忆功能，特别容易患阿尔茨海默病 病理学。睡眠和锻炼都与情景记忆功能有关，包括模式分离 运营依赖于MTL。年轻人的证据表明，睡眠和锻炼都是独立的。 与记忆力辨别(模式分离的行为关联)有关，但尚不清楚它们是否 互动来做到这一点，以及通过什么机制。这些关系在高危老年人中是否发生了变化 对于阿尔茨海默氏症也是未知的。为了填补这一知识空白，拟议中的研究将记录高密度 夜间睡眠中的脑电(HdEEG)以测量特定的地形图(即局部) 表现为非快速眼动睡眠慢波活动(SWA)和快速睡眠纺锤体活动，给药 评估睡眠前后记忆辨别力以测量睡眠依赖性的记忆任务 巩固记忆，并从56名老年人收集评估锻炼频率和持续时间的问卷数据 阿尔茨海默病风险升高的成年人。高分辨率静息功能磁共振 之前从同一参与者队列中收集的成像(hr-rsfMRI)数据将被分析以测量 休眠状态网络模块化。该项目将解决三个具体目标：(1)确定当地 SWA的表达和快速纺锤波活动与老年人睡眠依赖记忆巩固相关 成年人，(2)确定网络模块化是否与睡眠依赖的记忆巩固和 老年人的局部睡眠表达，以及(3)确定运动是否与局部表达 SWA和快速磁盘轴活动以及网络模块化。该项目将为申请者提供全面的 接受记忆理论、高级统计建模和尖端分析方法方面的培训 HdEEG数据。这项研究和培训计划将为申请人进行独立的学术研究做好准备。 职业生涯，并将提供支持之间关系的神经生物学机制的新见解 阿尔茨海默病高危老年人的睡眠、锻炼和记忆巩固。由此得出的结论 该项目可以指导前瞻性锻炼和基于睡眠的干预研究，以改善记忆功能和 通过强调以下内容的重要性来告知降低阿尔茨海默病风险的公共卫生建议 睡吧。

PROJECT SUMMARY Alzheimer’s disease is a progressive form of dementia with no effective treatments. Episodic memory deficits are a defining cognitive symptom of Alzheimer’s disease, which may be related to changes in the medial temporal lobes (MTL). The MTL facilitates episodic memory function and is particularly vulnerable to Alzheimer’s disease pathology. Both sleep and exercise are linked to episodic memory function, including pattern separation operations reliant on the MTL. Evidence in young adults suggests that sleep and exercise are each independently linked to mnemonic discrimination (behavioral correlate of pattern separation), but it is unclear whether they interact to do so, and through what mechanisms. Whether these relationships are altered in older adults at-risk for Alzheimer’s disease is also unknown. To fill this knowledge gap, the proposed study will record high-density electroencephalography (hdEEG) during overnight sleep to measure the topographically specific (i.e., local) expression of non-rapid eye movement sleep slow-wave activity (SWA) and fast sleep spindle activity, administer a memory task assessing mnemonic discrimination prior to and following sleep to measure sleep-dependent memory consolidation, and collect questionnaire data assessing exercise frequency and duration from 56 older adults with heightened Alzheimer’s disease risk. High-resolution resting-state functional magnetic resonance imaging (hr-rsfMRI) data previously collected from this same participant cohort will be analyzed to measure resting-state network modularity. The project will address three specific aims: (1) determine whether local expression of SWA and fast spindle activity are associated with sleep-dependent memory consolidation in older adults, (2) determine whether network modularity is associated with sleep-dependent memory consolidation and local sleep expression in older adults, and (3) determine whether exercise is associated with local expression of SWA and fast spindle activity and network modularity. This project will provide the applicant with comprehensive training in memory theory, advanced statistical modelling, and cutting-edge analytical methods for hr-rsfMRI and hdEEG data. This research and training plan will prepare the applicant for an independent academic research career and will provide novel insights into the neurobiological mechanisms supporting the relationships among sleep, exercise, and memory consolidation in older adults at-risk for Alzheimer’s disease. Findings from this project could guide prospective exercise and sleep-based interventional studies to improve memory function and inform public health recommendations to reduce Alzheimer’s disease risk by underscoring the importance of sleep.