The VETSA Longitudinal MRI Twin Study of Aging

VETSA 纵向 MRI 双胞胎衰老研究

• 批准号: 6942612
• 负责人: WILLIAM S. KREMEN
• 金额: $ 108.15万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6942612
• 关键词: aging; behavioral /social science research tag; behavioral genetics; clinical research; cognition; gene expression; hippocampus; human middle age (35-64); human subject; longitudinal human study; magnetic resonance imaging; male; neuroanatomy; neuropsychological tests; neuropsychology; prefrontal lobe /cortex; twin /multiplet

DESCRIPTION: (provided by applicant) Midlife provides an invaluable baseline for changes associated with aging, but is rarely a focus of brain aging studies. We will perform a longitudinal MRI study of middle-aged twins focusing on distributed neural circuits comprising prefrontal cortex (PFC) and associated subcortical structures, and the hippocampus. These regions show significant age-related change and are linked to cognitive functions (executive functions, episodic memory) that are particularly important in aging. We will conduct comprehensive volumetric analyses, emphasizing parcellation of PFC and highly detailed analysis of hippocampal subregions. We will also measure cortical thickness, white matter hyperintensity volumes, generate cerebral blood volume and T2*-weighted maps of hippocampal subregions to index static neuronal function, and perform diffusion tensor imaging to examine the microstructural integrity of white matter. Evidence to date suggests that the latter 2 techniques may detect age related differences or predict future impairment even in the absence of volume changes. The proposed study builds on our funded "Longitudinal Twin Study of Cognition and Personality"-a single integrated project comprising 2 grants (AG 18386-012A1 & A2)-which we refer as the Vietnam Era Twin Study of Aging (VETSA). The VETSA is assessing 720 middle aged twin pairs from the Vietnam Era Twin Registry (1/2 in Sacramento, 1/2 in Boston); 360 pairs at age 51+/-1 and 360 pairs at age 56+/-1. The design calls for follow-up every 5 years. Assessments include a neurocognitive battery (working memory, cognitive inhibition, processing speed, episodic memory), personality/psychosocial measures, and health/medical measures (BP, ankle-ann index, pulmonary function, genotyping). Based on a broad conceptual model, the goals are to use the twin method to determine the extent of genetic factors, shared environmental factors, and unique environmental factors influencing these variables, and to explicate the bases of inter-relationships within and among domains using bivariate, multivariate, and longitudinal twin analytic approaches. Key advantages are beginning in midlife (before substantial age-related declines), and having only 2 large, narrow age cohorts to maximize power to detect within-person change over time. The proposed study will begin in VETSA year 2 and will have 300 of the VETSA twin pairs undergo MRIs. We will examine genetic and environmental influences on our MRI measures in midlife as well as their association with key VETSA measures in both longitudinal and cross-sectional analyses. We will also create a normative database-a library of scans-that will provide a unique and valuable resource for future researchers.

描述：（由申请人提供）中年为与衰老相关的变化提供了宝贵的基线，但很少是大脑衰老研究的重点。我们将对专注于包含前额叶皮层（PFC）和相关皮层结构和海马的分布式神经回路的中年双胞胎进行纵向MRI研究。这些区域显示出与年龄相关的显着变化，并与在衰老中尤为重要的认知功能（执行功能，情节记忆）相关。我们将进行全面的体积分析，强调对PFC的分析以及海马子区域的高度详细分析。我们还将测量皮层厚度，白质高强度体积，产生脑血容量和海马子区域的T2*加权图，以构成静态神经元功能，并执行扩散量张量成像以检查白质的微观结构完整性。迄今为止的证据表明，即使在没有体积变化的情况下，后两种技术也可能检测到与年龄相关的差异或预测未来的损害。拟议的研究基于我们资助的“认知和人格纵向双胞胎研究” - 一个综合项目，其中包括2个赠款（AG 18386-012A1＆A2） - 我们将其称为越南时代的衰老研究（VETSA）。 VETSA评估了越南双子登记处的720个中年双胞胎对（萨克拉曼多的1/2，波士顿的1/2）； 51岁+/- 1和360对的360对，年龄56 +/- 1。该设计要求每5年进行一次跟进。评估包括神经认知电池（工作记忆，认知抑制，处理速度，情节记忆），人格/社会心理措施以及健康/医疗措施（BP，脚踝ANN指数，肺功能，肺功能，基因型）。基于一个广泛的概念模型，目标是使用双重方法来确定遗传因素的程度，共享的环境因素以及影响这些变量的独特环境因素，并使用双方，多变量和纵向双胞胎分析方法来解释域内和域内之间相互关系的基础。关键优势是在中年开始的（在与年龄相关的大幅下降之前），并且只有2个大，年龄狭窄的人群可以最大程度地发挥能力来检测随着时间的变化。拟议的研究将从Vetsa 2年开始，并将有300对Vetsa双子对接受MRI。我们将检查中年MRI测量的遗传和环境影响，以及它们与纵向和横截面分析中的关键VETSA措施的关联。我们还将创建一个规范性数据库-A扫描库 - 将为未来的研究人员提供独特而宝贵的资源。