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一个宝贵的基线，但很少是大脑老化研究的重点。我们将对中年双胞胎进行纵向MRI研究，重点关注分布的神经回路，包括前额叶皮质(PFC)和相关的皮质下结构，以及海马体。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，而认知功能在衰老过程中尤为重要。我们将进行全面的体积分析，重点是PFC的分割和对海马亚区的高度详细的分析。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亚区T2*加权图以指示静态神经元功能，并进行扩散张量成像以检查白质的微结构完整性。到目前为止的证据表明，即使在没有音量变化的情况下，后两种技术也可以检测与年龄相关的差异或预测未来的损害。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--一个单一的综合项目，包括两笔赠款(AG 18386-012A1和A2)--我们称之为越南时代的双胞胎衰老研究(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)；360对51岁/1岁和360对56岁/1岁。该设计要求每5年进行一次跟踪。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/心理社会测量以及健康/医学测量(血压、踝关节指数、肺功能、基因分型)。基于一个广泛的概念模型，目标是使用孪生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、多变量和纵向孪生分析方法来阐明域内和域间相互关系的基础。关键的优势是从中年开始(在与年龄相关的大幅下降之前)，并且只有两个大的、狭窄的年龄段队列，可以最大限度地检测随着时间的推移个人内部的变化。这项拟议的研究将在Vetsa的第二年开始，并将让300对Vetsa双胞胎接受核磁共振检查。我们将在纵向和横断面分析中检查遗传和环境对中年MRI测量的影响，以及它们与关键的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--它将为未来的研究人员提供独特而宝贵的资源。

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.