Glucose homeostasis and the risk of Alzheimer's disease and Alzheimer's disease related dementias in the Multi-Ethnic Study of Atherosclerosis

动脉粥样硬化多种族研究中的血糖稳态以及阿尔茨海默病和阿尔茨海默病相关痴呆的风险

• 批准号: 10301850
• 负责人: Morgana Lee Mongraw-Chaffin
• 金额: $ 229.6万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10301850
• 关键词: Address; Adult; Affect; African American; Age; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amyloid beta-Protein; Ancillary Study; Area; Biological; Biological Markers; Blood Glucose; Brain; Caring; Cognition; Cognitive; Collection; Data; Dementia; Development; Diabetes Mellitus; Diurnal Rhythm; Enrollment; Ethnic Origin; Follow-Up Studies; Glucose; Glycosylated hemoglobin A; Goals; Gonadal Steroid Hormones; Health; Hispanics; Hypoglycemia; Impaired cognition; Individual; Insulin Resistance; Investigation; Knowledge; Link; Literature; Magnetic Resonance Imaging; Measurement; Measures; Metabolic; Multi-Ethnic Study of Atherosclerosis; Neurocognitive; Non-Insulin-Dependent Diabetes Mellitus; Normal Range; Obesity; Outcome; Participant; Pathology; Pathway interactions; Phenotype; Play; Population Heterogeneity; Positron-Emission Tomography; Prediabetes syndrome; Prevalence; Prevention; Prevention strategy; Primary Prevention; Public Health; Race; Research; Risk; Risk Factors; Role; Secondary Prevention; Structural defect; Thinness; Time; Vascular Diseases; Visceral fat; Visit; Weight; White Matter Disease; Woman; adjudication; aged; aging population; blood glucose regulation; cardiometabolic risk; cardiometabolism; cardiovascular risk factor; cerebrovascular; clinical care; clinical examination; cognitive function; cognitive testing; cohort; dementia risk; disorder control; disorder risk; fasting glucose; glucose monitor; glycemic control; high risk; men; mild cognitive impairment; multi-ethnic; neuroimaging; novel marker; prevent; sex; standard of care; wearable device; β-amyloid burden

PROJECT SUMMARY Alzheimer’s disease and Alzheimer’s disease related dementias pose an enormous public health challenge. In the absence of a cure, prevention or delay of pathology offers the most promising avenue to control the disease. Despite growing recognition that cardiometabolic risk factors are major contributors to cognitive decline, Alzheimer’s disease, and Alzheimer’s disease related dementias, many gaps remain in our understanding of the mechanisms and pathways between glucose homeostasis and cognitive function. While type 2 diabetes (T2D) is increasingly recognized as a major preventable risk factor for Alzheimer’s disease and related dementias, intensive glucose control in T2D has not been shown to prevent cognitive decline in trials. This finding and inconsistent results for the influence of glucose control (HbA1c) on cognitive decline pose the question: What aspects of dysglycemia, and its inverse glucose homeostasis, increase the risk of Alzheimer’s disease or related dementias? This study’s overall goal is to investigate the role of dysglycemia across the glucose spectrum on incident neurocognitive markers of Alzheimer’s disease and Alzheimer’s disease related dementias in a multi-ethnic cohort: The Multi-Ethnic Study of Atherosclerosis (MESA). MESA enrolled 6814 men and women beginning in 2000. MESA participants have been extensively studied with respect to cardiovascular risk factors and outcomes and MESA-MIND, a cognitive ancillary, adds comprehensive cognitive testing and neuroimaging including brain MRI and amyloid β PET scans. MESA has a 7th exam occurring between 2021-2023 that will be concordant with the second MESA-MIND visit. While fasting glucose was obtained at every exam, and HbA1C and HOMA-IR measured at some exams, continuous glucose has not been measured. Adding continuous glucose monitoring wearable technology to MESA Exam 7 and repeated two years later provides a unique and timely opportunity to answer challenging questions about the role of dysglycemia that continue to impede the development of successful prevention strategies for Alzheimer’s disease and Alzheimer’s disease related dementias. This study will also add new measurements of insulin resistance (HOMA-IR). This ancillary to MESA will 1) Investigate the antecedent determinants of glucose homeostasis (from continuous glucose monitors at Exam 7 (n=2000) and change over two years (n=1000), 2. Determine whether continuous glucose markers of glucose homeostasis, dysglycemia, and change over time are associated with incident neurocognitive indicators of Alzheimer’s disease or Alzheimer’s disease related dementias (n=2000), and 3. Investigate the contributions of dysglycemia to Alzheimer’s disease and related dementia pathologies by sex and race/ethnicity (n=2000). Findings from this research will identify new mechanisms for the development of Alzheimer’s disease and Alzheimer’s disease related dementias, discover new primary and secondary prevention targets, and have the potential to change clinical care.

项目摘要 阿尔茨海默氏病和阿尔茨海默氏病与痴呆症相关的痴呆症提出了巨大的公共卫生挑战。在 缺乏治愈，预防或病理延迟提供了控制最有前途的途径 疾病。尽管越来越认识到心脏代谢危险因素是认知的主要因素 衰落，阿尔茨海默氏病和阿尔茨海默氏病有关的痴呆症，我们 了解葡萄糖稳态和认知功能之间的机制和途径。尽管 2型糖尿病（T2D）越来越被认为是阿尔茨海默氏病和 相关痴呆症，T2D中的密集葡萄糖控制尚未证明可以防止试验的认知能力下降。 葡萄糖控制（HBA1C）对认知下降的影响的发现和不一致的结果构成 问题：血糖症的哪些方面及其相反的葡萄糖稳态，增加了患的风险 阿尔茨海默氏病还是相关的痴呆症？这项研究的总体目标是调查血糖的作用 整个阿尔茨海默氏病和阿尔茨海默氏病的神经认知标记的葡萄糖谱 多种族队列中与疾病相关的痴呆症：动脉粥样硬化的多种族研究（MESA）。台面 从2000年开始就注册了6814名男女。Mesa参与者与 尊重心血管危险因素和结果以及一种认知辅助的梅萨（Mesa） 全面的认知测试和神经影像学包括脑MRI和淀粉样蛋白βPET扫描。梅萨有 在2021 - 2023年之间进行的第七次考试将与第二次台面访问一致。尽管 每次考试都获得了禁食葡萄糖，在某些考试中测量了HBA1C和HOMA-IR，继续 葡萄糖尚未测量。将连续的葡萄糖监测可穿戴技术添加到MESA考试 7并在两年后重复提供了一个独特而及时的机会，以回答有关的挑战问题 降血糖的作用继续阻碍成功的预防策略 阿尔茨海默氏病和阿尔茨海默氏病有关的痴呆症。这项研究还将增加新的测量 胰岛素抵抗（HOMA-IR）。台面的辅助措施将1）调查 葡萄糖稳态（从考试7（n = 2000）进行连续葡萄糖监测器，并在两年内变化 （n = 1000），2。确定是否连续 随着时间的流逝，变化与阿尔茨海默氏病或​​阿尔茨海默氏病的事件神经认知指标有关 与疾病相关的痴呆症（n = 2000）和3。研究血糖症对阿尔茨海默氏症的贡献 性别和种族/种族的疾病和相关痴呆症病理学（n = 2000）。这项研究的结果将 确定有关阿尔茨海默氏病和阿尔茨海默氏病有关的新机制 痴呆症，发现新的原发性和次要预防目标，并有可能改变临床 关心。