The VETSA Longitudinal MRI Twin Study of Aging

描述（由申请人提供）：目前大多数基于神经影像学研究的关于人类大脑衰老的知识只是从横断面数据推断出来的。尽管有几项研究表明中年是大脑衰老的关键拐点，但纵向成像研究很少，对中年的关注也相对较少。在纵向设计中，基因和环境对大脑衰老的影响程度就更少了。拟议的研究将通过VETSA纵向MRI孪生衰老研究（VMRI）的第一个5年随访来填补这些关键的知识空白。（VETSA是越南时代双胞胎衰老研究的缩写。）我们招募了607对双胞胎，并在基线VMRI中获得了515（85%）可分析的扫描，包括全面的结构和扩散张量成像。我们建议在第一次随访研究中替换部分受试者并获得600次扫描。在基线评估时，双胞胎的年龄为51-60岁，在拟议的VMRI随访中将为56-65岁。由于样本大，年龄范围窄，我们将有最大的力量来研究在这个关键的过渡时期的个人内部变化和变化的个体差异。具体目标是：1)在我们独特的规范数据库中添加纵向成像组件；2)确定基因和环境对大脑结构随时间变化的影响；3)研究APOE基因型与脑结构随时间变化的关系；4)阐明与大脑结构随时间变化相关的生物医学和其他危险因素，并检查它们共同的遗传和环境基础；5)提供白质随年龄变化的详细特征；6)通过研究区域灌注（通过动脉自旋标记）和默认网络（通过功能性MRI）来检查脑功能和区域脑活动的整合。潜在的风险/保护因素可在母体项目中收集的广泛的认知、生物医学和社会心理表型中获得。根据双因素模型，我们提出正常衰老主要影响额纹状体系统，而阿尔茨海默病对内侧颞叶系统的影响更大。白质完整性被假设为功能连接的基础，但只存在横截面证据。我们假设，基线白质完整性和白质完整性随时间的变化将预测默认网络主要组成部分之间活动相关性的强度。基于我们目前的发现，我们还预测APOE-54携带者前额叶区域的皮质变薄程度更高。该项目在确定成功或病理性脑衰老的早期预测因素并描述其相对潜在的遗传和环境影响方面具有独特的地位。相关性：该项目为理解中年（一个未被充分研究的时期）开始的大脑衰老过程创造了宝贵的资源。此外，在中年而不是在晚年确定预测因素的可能性，在干预或预防方面具有重要的公共卫生意义。该项目为了解中年（一个未被充分研究的时期）开始的大脑衰老过程创造了宝贵的资源。此外，在中年而不是晚年确定大脑衰老的预测因素的可能性，在干预或预防方面具有重要的公共卫生意义。

DESCRIPTION (provided by applicant): Most of what is currently known about human brain aging based on neuroimaging studies is only inferred from cross-sectional data. There have been very few longitudinal imaging studies and relatively little focus on middle age, despite the fact that several studies suggest that midlife is a key inflection point for brain aging. Even less is known about the extent of genetic and environmental influences on brain aging within a longitudinal design. The proposed study will fill these critical knowledge gaps with the first 5-year follow-up of The VETSA Longitudinal MRI Twin Study of Aging (VMRI). (VETSA is an acronym for Vietnam Era Twin Study of Aging.) We enrolled 607 twins and obtained 515 (85 percent) analyzable scans in the baseline VMRI with comprehensive structural and diffusion tensor imaging. We propose to replace some subjects and acquire 600 scans in this first follow-up study. Twins were 51-60 years old at the baseline assessment and will be 56-65 in the proposed VMRI follow-up. Given the large sample and narrow age range, we will have maximal power to examine within-person change and individual differences in change during this key transition period. Specific aims are to: 1) add a longitudinal imaging component to our unique normative database; 2) determine genetic and environmental influences on brain structure changes over time; 3) examine the relationship of APOE genotype to changes in brain structure over time; 4) elucidate biomedical and other risk factors related to changes in brain structure over time, and examine their shared genetic and environmental underpinnings; 5) provide detailed characterization of white matter changes with age; and 6) examine brain function and integration of regional brain activity by studying regional perfusion (via arterial spin labeling) and the default network (via functional MRI). Potential risk/protective factors are available in the extensive cognitive, biomedical, and psychosocial phenotypes collected in the parent project. In keeping with a 2-factor model, we propose that normal aging primarily affects frontal-striatal systems whereas the medial temporal system is more strongly affected in Alzheimer's disease. White matter integrity is hypothesized to underlie functional connectivity, but there exists only cross-sectional evidence. We hypothesize that baseline white matter integrity and change in white matter integrity over time will predict the strength of activity correlations between major components of the default network. Based on our current findings, we also predict greater cortical thinning in prefrontal regions in APOE-54 carrier. The proposed project is in a unique position to identify early predictors of successful or pathological brain aging and delineate their relative underlying genetic and environmental influences. Relevance: This project creates an invaluable resource for understanding the course of brain aging beginning in midlife (an understudied period). Moreover, the possibility of identifying predictors in midlife, rather than in later life, has important public health implications with regard to intervention or prevention. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE This project creates an invaluable resource for understanding the course of brain aging beginning in midlife (an understudied period). Moreover, the possibility of identifying predictors of brain aging in midlife, rather than in later life, has important public health implications with regard to intervention or prevention.