Use of 7T multimodal imaging to detect brain changes associated with light therapy in persons with mild cognitive impairment and mild Alzheimer's Disease

项目摘要/摘要 睡眠不佳与老年人的记忆功能下降有关，包括轻度认知障碍的老年人 损害(MCI)、阿尔茨海默病(AD)和相关痴呆症(ADRD)，这会减少睡眠 在健康和病理性衰老中对认知处理和记忆的关键贡献。我们队有 开发了一种有效的照明干预疗法(LIT)来改善睡眠和行为结果 ADRD患者住在疗养院，但LIT在大脑中工作的机制并不完全 明白了。要了解LIT使这些患者受益的机制，一个敏感而精确的工具是 需要检测和测量大脑关键区域的体积、连接性和功能的变化。这个 目前的应用建议使用高分辨率多模式7T成像来研究LIT对 轻度认知障碍和轻度阿尔茨海默病患者的睡眠生理和脑结构、功能和连接性。这项技术 将使我们能够产生异常高分辨率、高对比度的图像，揭示微妙的结构和 低于常规MRI可检测阈值的功能异常。通过这项研究的2 我们将检验以下假设：1)LIT将对大脑区域和回路产生可测量的影响 与AD病理有关；2)LIT将改善睡眠数量和质量、认知、情绪和睡眠质量 寿命与对照组相比；3)这些改进将与量化差异测量相关；以及 4)与对照组相比，LIT对大脑结构的影响较小。目标1将包括纵向的 活动和对照LITS在25例MCI或轻度AD患者中的交叉7T成像研究 以及优化的多模式7T成像协议，旨在捕获AD涉及的解剖结构 病理生理学和光照，测量LIT对睡眠和认知的影响。AIM 2将分析 照明干预前、后与对照照明干预数量差异的相关性 成像测量(区域体积、功能和扩散连通性以及图论指标)和PET， 睡眠(动图)和神经心理测量。这是第一次应用成像技术来跟踪效果 轻度阿尔茨海默病和轻度阿尔茨海默病。我们计划应用7T成像来提供一个高度敏感的窗口来了解 LIT可以改善睡眠和认知，潜在地延缓疾病进展和提高质量 MCI和AD患者的生活质量。

PROJECT SUMMARY/ABSTRACT Poor sleep is associated with decreased memory functioning in older adults, including those with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) and related dementias (ADRD), which diminishes sleep’s critical contribution to cognitive processing and memory in healthy and pathological aging. Our team has developed an effective lighting intervention therapy (LIT) for improving sleep and behavioral outcomes in ADRD patients living in nursing homes, but the mechanisms by which LIT works in the brain are not completely understood. To understand the mechanisms by which LIT benefits these patients, a sensitive and precise tool is required to detect and measure changes in the volumes, connectivity, and function of key brain regions. The current application proposes to use high-resolution multi-modal 7T imaging to investigate the impact of LIT on sleep physiology and brain structure, function, and connectivity in MCI and mild AD patients. This technique will enable us to produce exceptionally high-resolution, high-contrast images that reveal subtle structural and functional abnormalities that are below the detectability threshold of conventional MRI. Through the study’s 2 aims, we will test the following hypotheses: 1) LIT will induce measurable effects on brain regions and circuits associated with AD pathology; 2) LIT will improve sleep quantity and quality, cognition, mood, and quality of life compared to controls; 3) these improvements will correlate with quantitative difference measurements; and 4) LIT will show reduced effects on brain structures compared to control. Aim 1 will comprise a longitudinal crossover 7T imaging study applying the active and control LITs on a group of 25 patients with MCI or mild AD along with an optimized multi-modal 7T imaging protocol designed to capture the anatomy involved in AD pathophysiology and light exposure, measuring the LIT’s effect on sleep and cognition. Aim 2 will analyze correlations between the pre- and post-active and control lighting interventions’ differences in quantitative imaging measures (regional volumes, functional and diffusion connectivity, and graph theory metrics) and PET, sleep (actigraphy) and neuropsychological measures. This is the first application of imaging to track the effect of LIT in MCI and mild AD. We plan to apply 7T imaging to provide a highly sensitive window into the degree to which LIT may improve sleep and cognition and potentially delay disease progression and improve quality of life for patients with MCI and AD.