Early life glycemic status and Alzheimer's disease neuroimaging markers in middle age: the Bogalusa Heart Study

早期血糖状况和中年阿尔茨海默病神经影像学标志物：Bogalusa 心脏研究

基本信息

批准号：
10318574
负责人：
Lydia Bazzano
金额：
$ 69.47万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-02-15 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10318574
关键词：
20 year old Address Adolescence Adolescent Adult Affect African American African American population Age Age-Years Alzheimer&apos s Disease Amyloid Attenuated Automobile Driving Biological Blood Glucose Brain Cerebrovascular Circulation Cerebrovascular Disorders Cerebrum Child Childhood Chronic Clinical Code Cognition Disorders Cognitive Complex Data Digit structure Elderly Functional Magnetic Resonance Imaging Glucose Growth Guidelines Health behavior Heart Hyperglycemia Impaired cognition Impaired fasting glycaemia Individual Insulin Resistance Knowledge Lead Life Life Cycle Stages Life Style Memory Metabolic Metabolic dysfunction Minority Modification Molecular Molecular Target Neurobiology Neurocognitive Neuronal Injury Non-Insulin-Dependent Diabetes Mellitus Normal Range Obesity Outcome Overweight Participant Peripheral Physical activity Population Positron-Emission Tomography Prevalence Prevention Protocols documentation Race Risk Risk Factors Standardization Structure Testing Time Uncertainty Unhealthy Diet White Matter Hyperintensity Woman biracial brain magnetic resonance imaging clinical diagnosis cognitive change cognitive performance cognitive testing early childhood effective therapy executive function fasting plasma glucose fluorodeoxyglucose positron emission tomography functional outcomes gray matter improved men middle age modifiable risk neuroimaging neuroimaging marker prevent prospective sex young adult

项目摘要

The U.S. population greater than 65 years of age is estimated to grow from 46 million in 2014 to 88 million in 2050, and that growth has paralleled dramatic increases in prevalence of Alzheimer's disease (AD) and other late life cognitive syndromes. To date, there is no effective treatment to stall or reverse late life cognitive decline. Therefore, prevention, through modification of risk factors, is an essential strategy. Metabolic dysfunction, which often culminates in a clinical diagnosis of type 2 diabetes mellitus (T2DM) or pre-T2DM, is one such modifiable risk factor that is highly prevalent. However, while metabolic dysfunction itself is modifiable, it is not clear how to optimally prevent adverse and potentially long-lasting effects of metabolic dysfunction on the brain. The knowledge gap driving this uncertainty is incomplete understanding of the complex, bi-directional relationships between peripheral and central mechanisms of neuronal injury associated with metabolic dysfunction. Adverse health behaviors (e.g., poor diet and inadequate physical activity) induce adverse peripheral changes (e.g., insulin resistance, chronic hyperglycemia) as well as adverse brain changes (e.g., glucose hypometabolism, amyloid accumulation, and cerebrovascular dysfunction). Brain changes culminate in adverse cognitive changes that in turn may promote the adverse health behaviors. It has been long recognized that early life factors can have lasting consequences, yet it is unknown whether glycemic status in childhood and adolescence is an important trigger of cognitive changes decades later, and whether such cognitive changes are driven by AD-related neurobiological substrates like amyloid. The Bogalusa Heart Study (BHS) is the only on-going, life-course study of a biracial (35% African American/65% white; 13% T2DM, 35% pre-T2DM) U.S. population, with detailed, prospectively-collected assessments of metabolic status from early childhood through mid-life, and cognitive performance data at two time points in midlife (average age of 45 years) among 1,298 men and women. This project will use neuroimaging and cognitive testing to explore long- term cognitive outcomes (among 600 BHS participants) associated with high-normal early-life mean Fasting Plasma Glucose (mFPG), as well as AD-related neurobiological substrates for these outcomes (a subset of 250 BHS participants will also undergo 3T brain MRI and PET). The results of this study could impact FPG guidelines among adolescents and whether glycemic treatment should to be initiated avoid long-term adverse brain outcomes. The project will also assess whether AD-related molecular targets may be modified to block the impact on the brain of early life high-normal mFPG.

美国 65 岁以上人口预计将从 2014 年的 4600 万增加到 2014 年的 8800 万。到 2050 年，这种增长与阿尔茨海默氏病 (AD) 和其他疾病的患病率急剧增加同时发生。晚年认知综合症。迄今为止，还没有有效的治疗方法可以阻止或逆转晚年认知能力衰退。因此，通过改变危险因素进行预防是一项重要策略。代谢功能障碍，通常最终导致 2 型糖尿病 (T2DM) 或 T2DM 前期的临床诊断一种非常普遍的可改变的风险因素。然而，虽然代谢功能障碍本身可以修改，目前尚不清楚如何最佳地预防代谢的不利和潜在的长期影响大脑功能障碍。造成这种不确定性的知识差距是对神经元损伤相关的外周和中枢机制之间复杂的双向关系伴有代谢功能障碍。不良的健康行为（例如不良饮食和身体活动不足）会导致不良的外周变化（例如胰岛素抵抗、慢性高血糖）以及不良的大脑变化（例如，葡萄糖代谢低下、淀粉样蛋白积累和脑血管功能障碍）。大脑变化最终导致不良的认知变化，进而可能促进不良的健康行为。它一直长期以来人们认识到早期生活因素可能会产生持久的后果，但尚不清楚血糖状况是否会产生持久的影响。童年和青少年时期的认知变化是几十年后认知变化的重要触发因素，而这种变化是否认知变化是由淀粉样蛋白等 AD 相关神经生物学底物驱动的。博加卢萨心脏研究 (BHS) 是唯一一项针对混血儿（35% 非裔美国人/65% 白人；13% T2DM，35% T2DM 之前）美国人群，从早期就详细、前瞻性地收集代谢状态评估童年到中年，以及中年两个时间点的认知表现数据（平均年龄 45 岁）年），共 1,298 名男性和女性。该项目将使用神经影像学和认知测试来探索长期与高正常早期平均禁食相关的长期认知结果（600 名 BHS 参与者）血浆葡萄糖 (mFPG) 以及这些结果的 AD 相关神经生物学底物（250 个子集） BHS 参与者还将接受 3T 脑部 MRI 和 PET）。这项研究的结果可能会影响 FPG 青少年指南以及是否应该开始血糖治疗以避免长期不良反应大脑结果。该项目还将评估 AD 相关分子靶点是否可以被修改以阻止生命早期高正常 mFPG 对大脑的影响。