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

使用 7T 多模态成像检测轻度认知障碍和轻度阿尔茨海默病患者与光疗相关的大脑变化

• 批准号: 10539558
• 负责人: Priti Balchandani
• 金额: $ 25.35万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10539558
• 关键词: Affect; Agitation; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amygdaloid structure; Amyloid beta-Protein; Anatomy; Atrophic; Biological Clocks; Blood flow; Brain; Brain region; Chronobiology; Cognition; Cognitive; Custom; Dementia; Diffusion; Dimensions; Disease Progression; Elderly; Exposure to; Functional disorder; Hippocampus (Brain); Hypothalamic structure; Image; Intervention; Light; Lighting; Magnetic Resonance Imaging; Measurable; Measurement; Measures; Memory; Mental Depression; Methods; Monitor; Moods; Multimodal Imaging; Neurobiology; Neuronal Plasticity; Neuropsychology; Nursing Homes; Patients; Perfusion Weighted MRI; Persons; Photosensitivity; Phototherapy; Plant Roots; Positron-Emission Tomography; Protocols documentation; Quality of life; Resolution; Retina; Retinal Ganglion Cells; Risk; Short-Term Memory; Sleep; Sleep Deprivation; Structure; Techniques; Testing; Therapeutic Intervention; Ventral Tegmental Area; Work; Wrist; actigraphy; active control; behavioral outcome; cerebral atrophy; contrast imaging; design; graph theory; healthy aging; imaging study; improved; insight; locus ceruleus structure; long term memory; magnetic field; mild cognitive impairment; multidisciplinary; multimodality; nervous system disorder; neuroimaging; neurotransmission; pathological aging; poor sleep; quantitative imaging; sleep physiology; sleep quality; sleep quantity; suprachiasmatic nucleus; tool

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.

项目摘要/摘要 睡眠不佳与老年人的记忆功能降低有关，包括那些患有轻度认知的人 障碍（MCI）和阿尔茨海默氏病（AD）和相关痴呆症（ADRD），这会减少睡眠 在健康和病理衰老中对认知处理和记忆的关键贡献。我们的团队有 开发了有效的照明干预疗法（LIT），以改善睡眠和行为结果 居住在护士家中的ADRD患者，但在大脑中发挥作用的机制并不完全 了解点亮使这些患者受益的机制，一种敏感而精确的工具是 需要检测和衡量关键大脑区域的体积，连通性和功能的变化。 当前的申请建议使用高分辨率多模式7T成像来研究点亮对 MCI和轻度AD患者的睡眠生理和大脑结构，功能和连通性。这项技术 将使我们能够产生异常高分辨率的高对比度图像，这些图像揭示了微妙的结构和 低于常规MRI的可检测性阈值的功能异常。通过研究的2 目的，我们将测试以下假设：1）点亮将对大脑区域和电路产生可测量的影响 与AD病理相关； 2）点亮将改善睡眠数量和质量，认知，情绪和质量 与对照相比，生活； 3）这些改进将与定量差异测量相关；和 4）与对照相比，LIT将显示对大脑结构的影响减少。 AIM 1将完成纵向 跨界7T成像研究应用了25例MCI或轻度AD患者的主动和对照lits 以及优化的多模式7T成像协议，旨在捕获与AD有关的解剖结构 病理生理学和光暴露，衡量LIT对睡眠和认知的影响。 AIM 2将分析 活性和控制照明干预措施之间的相关性在定量方面存在差异 成像测量（区域体积，功能和扩散连接性以及图理论指标）和PET，PET 睡眠（行动学）和神经心理学措施。这是成像跟踪效果的第一个应用 在MCI和轻度广告中点亮。我们计划应用7T成像以提供高度敏感的窗口 点亮可以改善睡眠和认知，并可能延迟疾病的进展并提高质量 MCI和AD患者的寿命。