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.

项目总结/摘要 睡眠不好与老年人记忆功能下降有关，包括那些轻度认知障碍的人。 睡眠障碍（MCI）和阿尔茨海默病（AD）及相关痴呆（ADRD）， 对健康和病理老化中的认知处理和记忆有重要贡献。我们的团队已被 开发了一种有效的照明干预疗法（LIT），用于改善睡眠和行为结果， 生活在疗养院的ADRD患者，但LIT在大脑中工作的机制并不完全 明白为了了解LIT使这些患者受益的机制，一个敏感而精确的工具是 需要检测和测量关键大脑区域的体积，连接和功能的变化。的 当前申请提出使用高分辨率多模态7 T成像来研究LIT对 MCI和轻度AD患者的睡眠生理学和脑结构、功能和连通性。这种技术 将使我们能够产生非常高的分辨率，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。通过研究，2 为了达到这一目的，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病理学相关; 2）LIT将改善睡眠数量和质量，认知，情绪和睡眠质量。 3）这些改善将与定量差异测量相关;以及 4)与对照组相比，LIT对大脑结构的影响降低。目标1将包括纵向 对一组25例MCI或轻度AD患者应用活性和对照LIT的交叉7 T成像研究 沿着优化的多模式7 T成像方案，旨在捕获AD涉及的解剖结构 病理生理学和光暴露，测量LIT对睡眠和认知的影响。目标2将分析 前和后主动和控制照明干预的定量差异之间的相关性 成像测量（区域体积、功能和扩散连接性以及图论度量）和PET， 睡眠（活动记录）和神经心理学测量。这是第一次应用成像技术来追踪 LIT在MCI和轻度AD中的作用。我们计划应用7 T成像来提供一个高度敏感的窗口， LIT可以改善睡眠和认知，并可能延缓疾病进展和改善质量 对于MCI和AD患者来说，