The VETSA Longitudinal MRI Twin Study of Aging (VETSA MRI 4)

VETSA 纵向 MRI 双胞胎衰老研究 (VETSA MRI 4)

• 批准号: 10419498
• 负责人: WILLIAM S. KREMEN
• 金额: $ 187.27万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10419498
• 关键词: Adult; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid beta-Protein; Biological Markers; Brain; Brain Pathology; Brain region; Cerebrovascular Circulation; Cerebrovascular Disorders; Cognition; Cognitive; Consensus; Data; Data Collection; Dementia; Deposition; Development; Diabetes Mellitus; Diffusion Magnetic Resonance Imaging; Disease; Disease Marker; Disease Progression; Early identification; Education; Elderly; Etiology; Funding; Genetic; Genetic Variation; Genotype; Goals; Grant; Health; Hour; Hypertension; Impaired cognition; Individual; Knowledge; Link; Longevity; Magnetic Resonance Imaging; Measures; Mediating; Medical; Modality; Nerve Degeneration; Onset of illness; Outcome; Participant; Pathologic; Pathology; Pattern; Perfusion; Phase; Plasma; Population; Positioning Attribute; Process; Public Health; Quality Control; Quality of life; Resources; Risk; Risk Factors; Sampling; Savings; Signal Transduction; Site; Smoking; Source; Sum; Testing; Thick; Time; Twin Multiple Birth; Twin Studies; United States National Institutes of Health; Vietnam; White Matter Hyperintensity; Work; aging brain; apolipoprotein E-4; arterial spin labeling; base; cerebrovascular; cerebrovascular health; cerebrovascular pathology; cohort; cost; data acquisition; design; genome-wide; human old age (65+); hypoperfusion; improved; in vivo; indexing; interest; locus ceruleus structure; middle age; mild cognitive impairment; modifiable risk; multimodality; neuroimaging; novel; prevent; prodromal Alzheimer' s disease; protective factors; psychosocial; tau Proteins; tau-1; vascular risk factor; virtual

PROJECT SUMMARY/ABSTRACT Alzheimer’s disease (AD) is costly and burdensome. As the US population ages, AD’s public health impact continues to grow. NIH and Alzheimer’s Association consensus statements indicate that understanding early phases of disease progression—such as mild cognitive impairment (MCI)—beginning in middle age is key to slowing dementia onset. Identifying at-risk individuals early is also estimated to result in massive savings. Despite the protracted progression of AD brain pathology, little is known about its temporal course from middle to older age, particularly for neuroimaging indices. The Vietnam Era Twin Study of Aging (VETSA) focuses on early identification of risk for MCI/AD and AD-related brain changes beginning when subjects were in their 50s. The proposed VETSA MRI wave 4 project, with a mean age of 74 (67-78), occurs during a time of increased incident MCI/AD. That, in combination with our longitudinal data, allows for improved ability to determine neuroimaging correlates, trajectories, and their predictors. Continued data collection will allow us to examine the transition period from pre- to post-disease onset and expand on prediction from midlife for an increasing number of individuals. This project is linked to the funded general VETSA 4 grant (AG050595) which collects 10-12 hours per subject of cognitive, health/medical, psychosocial and biomarker data. In addition, we can elucidate genetic and environmental influences on these processes via combined twin and genome-wide genotyping/polygenic score data. We also capitalize on early (age 20) cognitive data, a unique feature enabling us to differentiate cognitive decline from longstanding differences. We request funds to cover MRI acquisition, processing, and analysis (n=500), leveraging associated ongoing work in the general VETSA 4 grant. Aims are: 1) Develop, validate, and characterize novel early brain indicators of risk for MCI/AD. We will develop and validate a novel AD brain signature based on diffusion MRI and show that this brain signature of adults who are only in their 50s improves prediction of progression to MCI. We also hypothesize that integrity of the locus coeruleus—the earliest brain site of tau deposition—will be another early, sensitive risk indicator. 2) Examine cerebrovascular risk factors and their relationship with cognition and AD biomarkers. Cerebrovascular disease (CVD) is the most common pathology concomitant with AD and may contribute to disease progression or be an independent source of brain and cognitive decline. We particularly focus on CVD markers of white matter hyperintensities and arterial spin labeling (ASL) perfusion. 3) Quantify the magnitude of neurodegeneration from midlife to early old age and its underlying genetic and environmental influences. We will examine genetic influences on longitudinal change in macro- and micro-structural brain measures. Our approach includes identifying mediating/moderating effects of risk factors across the lifespan and leveraging our twin and genome-wide genotype data. Covering ~18 years, this project will be a resource for advancing knowledge about early identification of risk for MCI/AD, with potential for a profound public health impact.

项目概要/摘要 阿尔茨海默病 (AD) 代价高昂且负担重，随着美国人口老龄化，AD 对公共健康造成影响。 美国国立卫生研究院 (NIH) 和阿尔茨海默病协会的共识声明表明，尽早了解。 中年开始的疾病进展阶段（例如轻度认知障碍 (MCI)）是关键 据估计，尽早识别高危人群也能减缓痴呆症的发病率，从而节省大量资金。 尽管 AD 脑部病理学进展缓慢，但对其从中年开始的时间进程知之甚少。 越南时代双胞胎衰老研究 (VETSA) 的重点是老年。 从受试者 50 多岁开始，尽早识别 MCI/AD 和 AD 相关大脑变化的风险。 拟议的 VETSA MRI 第 4 波项目的平均年龄为 74 岁（67-78 岁），发生在人口增加的时期 结合我们的纵向数据，可以提高确定事件 MCI/AD 的能力。 神经影像相关性、轨迹及其预测因子将使我们能够进行检查。 从疾病发生前到疾病发生后的过渡期，并扩大中年的预测，以增加 该项目与资助的一般 VETSA 4 赠款 (AG050595) 相关，该赠款收集 每个受试者 10-12 小时的认知、健康/医学、心理社会和生物标志物数据。 通过结合双胞胎和全基因组阐明遗传和环境对这些过程的影响 我们还利用早期（20 岁）认知数据，这是一个独特的功能。 使我们能够区分认知能力下降和长期存在的差异。我们请求资金来支付 MRI 费用。 采集、处理和分析 (n=500)，利用通用 VETSA 4 中相关的正在进行的工作 目标是： 1) 开发、验​​证和描述 MCI/AD 风险的新型早期大脑指标。 开发并验证一种基于扩散 MRI 的新型 AD 大脑特征，并表明该大脑特征 50 多岁的成年人可以提高对 MCI 进展的预测。我们还竞争这种完整性。 蓝斑（tau 蛋白沉积最早的大脑部位）的变化将是另一个早期、敏感的风险指标。 2) 检查脑血管危险因素及其与认知和 AD 生物标志物的关系。 脑血管疾病 (CVD) 是 AD 最常见的伴随病理，可能导致 疾病进展或成为大脑和认知能力下降的独立原因。我们特别关注心血管疾病。 白质高信号标记和动脉自旋标记 (ASL) 灌注 3) 量化幅度。 从中年到老年早期的神经退行性疾病及其潜在的遗传和环境影响。 我们将研究遗传对大脑宏观和微观结构测量纵向变化的影响。 方法包括识别风险因素在整个生命周期中的中介/调节作用并利用 我们的双胞胎和全基因组基因型数据涵盖约 18 年，将成为推动进步的资源。 有关早期识别 MCI/AD 风险的知识，可能对公共卫生产生深远影响。