Feasibility of Improving Glycemia to Prevent Alzheimer's Disease

改善血糖预防阿尔茨海默病的可行性

• 批准号: 10633688
• 负责人: Paige C Geiger
• 金额: $ 47.76万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10633688
• 关键词: Affect; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid; Bioenergetics; Biological Markers; Blood; Blood Glucose; Blood Pressure; Blood Vessels; Body mass index; Brain; Centers for Disease Control and Prevention (U.S.); Cerebrovascular Circulation; Cerebrum; Clinical; Clinical Trials; Cognitive; Continuous Glucose Monitor; Diabetes Mellitus; Diagnosis; Disease; Elderly; Endocytic Vesicle; Energy Metabolism; Etiology; Fibromyalgia; Glucose; Glycosylated Hemoglobin; Glycosylated hemoglobin A; Heat shock proteins; Human; Impairment; Individual; Inflammation; Insulin Resistance; Interleukin-10; Interleukin-6; Intervention; Link; Liquid substance; Magnetic Resonance Imaging; Maintenance; Measures; Metabolic; Metabolism; Mitochondria; Molecular Chaperones; Nerve Degeneration; Neurodegenerative Disorders; Neurofibrillary Tangles; Non-Insulin-Dependent Diabetes Mellitus; Organ; Outcome; Outcome Measure; Oxygen; Plasma; Populations at Risk; Positioning Attribute; Prediabetes syndrome; Quality Control; Rest; Risk; Risk Marker; Senile Plaques; Standardization; System; TNF gene; Testing; Therapeutic heat application; Time; Tissues; Translating; blood glucose regulation; brain health; experience; fasting glucose; fluorodeoxyglucose; glucose metabolism; glycemic control; human old age (65+); improved; indexing; insulin sensitivity; neuroimaging marker; neuropathology; novel therapeutics; post intervention; prevent; primary outcome; proteostasis; response; tau Proteins; uptake; vascular risk factor

Project Summary The impaired glycemic control associated with pre-diabetes increases risk for type 2 diabetes, which is a known risk factor for Alzheimer’s Disease (AD). Mechanisms such as impaired energy metabolism, cellular bioenergetic function, reduced intracellular protein homeostasis (proteostasis), and inflammation are all potential contributors to AD etiology. Therefore, a novel therapy that simultaneously improves glycemic control and cellular chaperone systems (i.e. Heat Shock Proteins, HSPs) may prove particularly effective in preventing and treating AD. Heat therapy has been independently shown to improve blood glucose regulation, insulin resistance, and inflammation. Importantly, heat therapy also activates inter-organ crosstalk via endocytic vesicles and increases HSPs to improve both mitochondrial function and proteostasis in a variety of tissues. Given the potential contribution of these factors to brain health, heat therapy could offer immense clinical benefit to individuals at risk for AD. Here, we will determine if heat therapy can improve blood (Aim 1) and brain (Aim 2) glucose metabolism in cognitively healthy older adults (65+) who are at risk for AD. We will also examine the degree to which changes in blood and brain glucose metabolism track together and explore several additional potential mechanisms that are critical to understanding the brain benefits of heat therapy (Aim 3). These aims will provide a comprehensive understanding of the impact of heat therapy on glucose homeostasis and brain health.

项目摘要 与糖尿病前期相关的血糖控制受损增加了2型糖尿病的风险，这是一种 阿尔茨海默病（AD）的已知危险因素。机制如能量代谢受损，细胞 生物能量功能、降低的细胞内蛋白质稳态（蛋白质稳态）和炎症都是 AD病因学的潜在贡献者。因此，一种同时改善血糖控制的新疗法 和细胞伴侣系统（即热休克蛋白，HSPs）可以证明在预防 以及治疗AD。热疗法已被独立证明可以改善血糖调节，胰岛素 抵抗和炎症。重要的是，热疗法还通过内吞作用激活器官间串扰。 囊泡和增加热休克蛋白，以改善线粒体功能和各种组织中的蛋白质稳定。 考虑到这些因素对大脑健康的潜在贡献，热疗法可以提供巨大的临床价值。 对有AD风险的个体有益。在这里，我们将确定热疗法是否可以改善血液（目标1）和大脑 (Aim 2）认知健康老年人（65岁以上）中有AD风险的葡萄糖代谢。我们还将 检查血液和大脑葡萄糖代谢变化的程度，并探索 几个额外的潜在机制，这是至关重要的理解热疗法的大脑效益 (Aim（3）第三章。这些目标将提供一个全面的了解热疗法对葡萄糖的影响 体内平衡和大脑健康。