The VETSA Longitudinal MRI Twin Study of Aging

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，但很少是脑衰老研究的重点。我们将对中年双胞胎进行纵向MRI研究，重点关注包括前额叶皮层（PFC）和相关皮层下结构以及海马体的分布式神经回路。这些区域显示出与年龄相关的显著变化，并与认知功能（执行功能、情景记忆）有关，这些功能在衰老过程中尤为重要。我们将进行全面的体积分析，强调PFC的分割和海马体亚区非常详细的分析。我们还将测量皮质厚度，白质高强度体积，生成脑血容量和海马亚区T2*加权图以索引静态神经元功能，并进行弥散张量成像以检查白质的微结构完整性。迄今为止的证据表明，后两种技术可以检测到与年龄相关的差异，或者即使在没有体积变化的情况下预测未来的损伤。这项拟议的研究建立在我们资助的“认知和人格纵向双胞胎研究”的基础上——一个由两笔拨款（AG 18386-012A1和A2）组成的单一综合项目——我们称之为越南时代双胞胎衰老研究（VETSA）。VETSA正在评估来自越南时代双胞胎登记处的720对中年双胞胎（一半在萨克拉门托，一半在波士顿）；51岁时360双+/-1 56岁时360双+/-1。该设计要求每5年随访一次。评估包括神经认知测试（工作记忆、认知抑制、处理速度、情景记忆）、人格/社会心理测试和健康/医疗测试（血压、踝-神经指数、肺功能、基因分型）。基于一个广泛的概念模型，目标是使用双胞胎方法来确定遗传因素、共享环境因素和独特环境因素对这些变量的影响程度，并使用双变量、多变量和纵向双胞胎分析方法来解释领域内部和领域之间相互关系的基础。关键的优势是在中年开始（在与年龄相关的实质性衰退之前），并且只有两个大的，狭窄的年龄队列，以最大限度地检测随时间推移的个人变化。拟议的研究将在VETSA第二年开始，将有300对VETSA双胞胎接受核磁共振成像。我们将在纵向和横断面分析中研究遗传和环境对中年MRI测量的影响，以及它们与关键VETSA测量的关联。我们还将创建一个规范的数据库——一个扫描库——这将为未来的研究人员提供一个独特而有价值的资源。

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.