The VETSA longitudinal twin study of cognition and aging

描述（由申请人提供）：越南时代双胞胎衰老研究（VETSA）研究提供了一个独特的机会来研究遗传和环境对早期认知变化和相关风险因素的影响。在VETSA 2中，我们建议对基线时为中年（50岁）的大型年龄同质样本进行5-6年的随访。认知衰老的纵向研究采用了年龄异质性样本的队列序列设计，通常倾向于老年受试者。有确凿的证据表明中年到老年早期会发生变化，但由于平均变化确实趋向于适度，因此提高检查个体差异的能力是关键。虽然没有一个单一的设计可以提供所有的答案，但我们的新设计确实增强了研究个体内部变化模式差异的能力。通过关注中年，我们的设计也增加了识别认知衰退早期预测因素的潜力。此外，我们还包括了一个客观的认知努力分配指标，这将是一个重要的指标，即使在没有表现变化的情况下。我们将在收集基线神经认知、生物医学和社会心理数据后对720对中年双胞胎（1440人）进行5-6年的随访。VETSA 2随访时的平均年龄为60岁（57-66岁）。2位主要研究者（clemen， UCSD; Lyons, Boston university）的申请组成了一个单一的综合项目。我们的重点是描述遗传和环境对早期认知努力和表现变化的影响（目标1,2），并研究介导或调节这些变化的主要因素：APOE[目标3]；其他生物医学风险[目标4]；生活方式/社会心理因素[目标5])。目标是：1)描述基因和环境对认知变化随时间变化的影响（以及驱动变化的特定组成过程）；2)研究认知效率（即绩效与努力资源分配的比率[基于任务诱发瞳孔反应]）作为关键的认知老化过程；3)检测APOE基因型与认知功能随时间变化的关系；4)阐明与认知相关的生物医学危险因素，确定最能预测认知衰老的特定健康危险因素（使用以前未使用的多变量遗传模型）；5)研究与认知衰老相关的生活方式和社会心理因素。我们将在多个领域获得全面的评估，利用一种将双胞胎方法与分析认知成分过程的实验/神经科学方法相结合的新方法，并使用一种具有成本效益的心理生理学方法（瞳孔测量法）来测量认知努力。公共卫生相关性：VETSA 2建立在VETSA 1的独特资源的基础上，为研究从中年（一个研究不足的领域）到早期老年的变化，以及理解生物和环境因素的相互作用，这些因素是衰老或成功衰老的关键早期预测因素，创造了宝贵的资源。VETSA 2项目建立在VETSA 1的独特资源的基础上，为研究中年（一个研究不足的领域）和理解生物和环境因素之间的相互作用创造了宝贵的资源，这些因素是成功衰老的关键决定因素。

DESCRIPTION (provided by applicant): The Vietnam Era Twin Study of Aging (VETSA) study provides a unique opportunity to examine genetic and environmental influences on early cognitive change and associated risk factors. In VETSA 2, we propose our first 5-6 year follow-up of a large, age-homogenous sample that was middle-aged (50s) at baseline. Longitudinal studies of cognitive aging have employed cohort-sequential designs with age-heterogeneous samples that are usually weighted toward older subjects. There is solid evidence of change in midlife to early old age, but because mean change does tend to be modest, increased ability to examine individual differences is key. While no single design can provide all the answers, our novel design does enhance the ability to study differences in within-individual change patterns. By focusing on midlife, our design also has increased potential to identify early predictors of cognitive decline. Moreover, we are including an objective measure of allocation of cognitive effort that will be an important indicator, even in the absence of performance changes. We will follow 720 middle-aged twin pairs (1440 individuals) 5-6 years after collection of baseline neurocognitive, biomedical, and psychosocial data. Mean age at our VETSA 2 follow-up will be 60 (57-66). Applications from 2 Principal Investigators (Kremen, UCSD; Lyons, Boston Univ.) comprise a single integrated project. Our focus is to characterize genetic and environmental influences on early age-related changes in cognitive effort and performance (Aims 1, 2), and to examine major factors that mediate or moderate those changes: APOE [Aim 3]; other biomedical risks [Aim 4]; lifestyle/psychosocial factors [Aim 5]). Aims are: 1) Characterize genetic and environmental influences on cognitive change over time (and specific component processes driving change); 2) Investigate cognitive efficiency (i.e., ratio of performance to effortful resource allocation [based on task-evoked pupillary responses]) as a key cognitive aging process; 3) Examine the relationship of APOE genotype to changes in cognitive function over time; 4) Elucidate biomedical risk factors related to cognition and identify specific health risk factors that best predict cognitive aging (with multivariate genetic models not previously used); 5) Examine lifestyle and psychosocial factors related to cognitive aging. We will obtain comprehensive assessments in multiple domains, utilize a novel approach that integrates the twin method with experimental/neuroscience approaches of parsing cognitive component processes, and use a cost-effective psychophysiological method (pupillometry) to measure cognitive effort. PUBLIC HEALTH RELEVANCE: VETSA 2 builds upon the unique resource of VETSA 1 and creates an invaluable resource for the study of change from midlife (an under-studied area) to early old age, and for understanding the interplay of biological and environmental factors that are key early predictors of declining or successful aging. The VETSA 2 project builds upon the unique resource of VETSA 1 and creates an invaluable resource for the study of midlife (an under-studied area) and for understanding the interplay of biological and environmental factors that are key determinants of successful aging.