The VETSA Longitudinal MRI Twin Study of Aging

描述(由申请人提供)：目前已知的大多数基于神经成像研究的人脑老化只从横断面数据中推断出来。尽管有几项研究表明中年是大脑老化的关键拐点，但很少有纵向成像研究，也相对较少关注中年。在纵向设计中，遗传和环境对大脑老化的影响程度更是鲜为人知。这项拟议的研究将通过Vetsa纵向MRI衰老双胞胎研究(VMRI)的第一个5年随访来填补这些关键知识空白。(Vetsa是越南时代双胞胎老龄化研究的首字母缩写。)我们招募了607名双胞胎，在基线VMRI中获得了515(85%)个可分析的扫描，并进行了全面的结构和扩散张量成像。在第一次后续研究中，我们建议替换一些受试者并获得600次扫描。双胞胎在基线评估时年龄在51-60岁之间，在拟议的VMRI后续行动中将在56-65岁之间。考虑到大样本和狭窄的年龄范围，在这个关键的过渡期，我们将拥有最大的权力来检查个人内部的变化和个人变化的差异。具体目标是：1)向我们独特的规范数据库添加纵向成像组件；2)确定遗传和环境对脑结构随时间变化的影响；3)检查APOE基因与脑结构随时间变化的关系；4)阐明与脑结构随时间变化相关的生物医学和其他风险因素，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；以及6)通过研究区域灌注(通过动脉旋转标记)和默认网络(通过功能磁共振)来检查脑功能和区域脑活动的整合。在母项目中收集的广泛的认知、生物医学和心理社会表型中存在潜在的风险/保护因素。与双因素模型一致，我们认为正常衰老主要影响额叶-纹状体系统，而内侧颞叶系统在阿尔茨海默病中受到更严重的影响。白质完整性被认为是功能连接的基础，但只存在横断面证据。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。根据我们目前的发现，我们还预测在APOE-54携带者的前额叶区域会有更大的皮质变薄。拟议的项目处于独特的位置，可以识别成功或病理性脑老化的早期预测因素，并描绘出它们相对潜在的遗传和环境影响。相关性：这个项目为理解从中年(一个研究不足的时期)开始的大脑老化过程创造了一个宝贵的资源。此外，在中年而不是在晚年确定预测因素的可能性，对干预或预防具有重要的公共卫生影响。公共卫生相关性：项目描述这个项目为理解从中年(一个研究不足的时期)开始的大脑老化过程创造了一个宝贵的资源。此外，确定中年而不是晚年大脑老化的预测因素的可能性，对于干预或预防具有重要的公共健康影响。

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.