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，但很少成为大脑衰老研究的焦点。我们将对中年双胞胎进行纵向 MRI 研究，重点关注包括前额皮质 (PFC) 和相关皮质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着变化，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其重要。我们将进行全面的体积分析，重点是 PFC 的分割和海马分区的高度详细分析。我们还将测量皮质厚度、白质高信号体积、生成脑血容量和海马分区的 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观结构完整性。迄今为止的证据表明，后两种技术即使在没有体积变化的情况下也可以检测与年龄相关的差异或预测未来的损伤。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，该项目是一个由两项资助（AG 18386-012A1 和 A2）组成的单一综合项目，我们将其称为越南时代双胞胎老龄化研究（VETSA）。 VETSA 正在评估越南时代双胞胎登记处的 720 对中年双胞胎（萨克拉门托 1/2，波士顿 1/2）； 51 /-1 岁时有 360 对，56 /-1 岁时有 360 对。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、情景记忆）、个性/社会心理测量和健康/医疗测量（血压、踝关节指数、肺功能、基因分型）。基于广泛的概念模型，目标是使用孪生方法来确定影响这些变量的遗传因素、共享环境因素和独特环境因素的程度，并使用双变量、多变量和纵向孪生分析方法阐明领域内和领域之间相互关系的基础。主要优势是从中年开始（在与年龄相关的大幅衰退之前），并且只有两个大而窄的年龄组，以最大限度地提高检测人体内随时间变化的能力。拟议的研究将于 VETSA 第 2 年开始，将对 300 对 VETSA 双胞胎进行 MRI 检查。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数据库（扫描库），为未来的研究人员提供独特且有价值的资源。

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.