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，我们建议对基线为中年(50多岁)的大样本进行5-6年的随访。认知老化的纵向研究采用了队列序贯设计，采用了年龄不同的样本，这些样本通常倾向于年龄较大的受试者。有确凿的证据表明，从中年到老年早期会发生变化，但由于平均变化往往是温和的，因此提高审视个体差异的能力是关键。虽然没有单一的设计可以提供所有的答案，但我们新颖的设计确实增强了研究个体内部变化模式差异的能力。通过专注于中年，我们的设计也增加了识别认知衰退的早期预测因素的可能性。此外，我们纳入了认知努力分配的客观衡量标准，这将是一个重要的指标，即使在没有业绩变化的情况下也是如此。我们将在收集基线神经认知、生物医学和心理社会数据后5-6年对720对中年双胞胎(1440人)进行跟踪调查。在我们的Vetsa 2随访中，平均年龄为60岁(57-66岁)。来自2名首席调查员的申请(克莱曼，加州大学洛杉矶分校；里昂，波士顿大学)包括一个单一的综合项目。我们的重点是表征遗传和环境对早期年龄相关认知努力和表现变化的影响(目标1、2)，并检查调节或缓和这些变化的主要因素：载脂蛋白E[目标3]；其他生物医学风险[目标4]；生活方式/心理社会因素[目标5])。目标是：1)描述遗传和环境对认知随时间变化的影响(以及驱动变化的特定组成部分过程)；2)调查认知效率(即，成绩与努力资源分配的比率[基于任务诱发的瞳孔反应])，作为一个关键的认知衰老过程；3)研究APOE基因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风险因素，并找出最能预测认知衰老的特定健康风险因素(使用以前未使用的多元遗传模型)；5)研究与认知衰老相关的生活方式和心理社会因素。我们将获得多个领域的综合评估，利用一种新的方法，将孪生方法与分析认知成分过程的实验/神经科学方法相结合，并使用一种经济有效的心理生理学方法(瞳孔测量法)来测量认知努力。

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.