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：
10064986
负责人：
Lydia Bazzano
金额：
$ 71.44万
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/10064986
关键词：
20 year old Address Adolescence Adolescent Adult Affect African American 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 Magnetic Resonance Imaging 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 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.

美国人口大于65岁以上的人口将从2014年的4600万增加到8800万 2050年，这种增长与阿尔茨海默氏病（AD）和其他的患病率显着增加晚年认知综合征。迄今为止，尚无有效的治疗方法来失速或扭转后期的认知衰退。因此，通过改变危险因素，预防是一个必不可少的策略。代谢功能障碍通常在2型糖尿病（T2DM）或T2DM的临床诊断中达到顶点高度普遍的一种可修改风险因素。但是，虽然代谢功能障碍本身是可修改，尚不清楚如何最佳防止代谢的不利和潜在持久影响大脑功能障碍。驱动这种不确定性的知识差距是对神经元损伤的外围和中心机制之间的复杂的双向关系具有代谢功能障碍。不利的健康行为（例如，饮食不良和体育锻炼不足）会引起不良周围变化（例如胰岛素抵抗，慢性高血糖）以及不良大脑的变化（例如，葡萄糖低代谢，淀粉样蛋白积累和脑血管功能障碍）。大脑变化最终导致不利的认知变化可能会促进不利的健康行为。它一直长期以来，早期的生活因素可能会带来持久的后果，但尚不清楚血糖状态是否在童年和青春期是认知变化几十年后的重要触发因素，以及这种情况是否如此认知变化是由淀粉样蛋白等广告相关的神经生物学底物驱动的。 Bogalusa心脏研究（BHS）是一个混血儿的唯一持续的生活课程（35％的非裔美国人/65％白人； 13％T2DM，35％ T2DM）美国人口，对早期的代谢状况进行了详细的，预期收集的评估童年通过中年，以及中年两个时间点的认知绩效数据（平均年龄为45岁年）在1,298名男女中。该项目将使用神经影像学和认知测试来探索长期术语认知结果（在600个BHS参与者中）与高正常的早期寿命相关血浆葡萄糖（MFPG）以及这些结果的与AD相关的神经生物学底物（250个子集 BHS参与者还将接受3T脑MRI和PET）。这项研究的结果可能会影响FPG 青少年的准则以及是否应开始血糖治疗避免长期不良大脑结果。该项目还将评估是否可以修改与广告相关的分子靶标的阻止对早期生命的大脑的影响高正常MFPG。