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检查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）的大型年龄均匀样本进行首次5-6年随访。认知老化的纵向研究采用队列序贯设计，年龄异质性样本通常偏向老年受试者。有确凿的证据表明中年到老年早期的变化，但由于平均变化往往是适度的，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能力下降早期预测因子的潜力。此外，我们还包括一个客观的衡量认知努力分配的指标，这将是一个重要的指标，即使在没有性能变化的情况下。我们将在收集基线神经认知、生物医学和社会心理数据后5-6年随访720对中年双胞胎（1440人）。VETSA 2随访时的平均年龄为60岁（57-66岁）。来自2名主要研究者（Kremen，UCSD;里昂，波士顿大学）的申请是一个单一的综合项目。我们的重点是描述遗传和环境对认知努力和表现的早期年龄相关变化的影响（目标1，2），并检查介导或缓和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/心理社会因素[目标5]）。目标是：1）表征随时间推移对认知变化的遗传和环境影响（以及驱动变化的特定组成过程）; 2）调查认知效率（即，表现与努力资源分配的比率[基于任务诱发的瞳孔反应]）作为关键的认知老化过程; 3）检查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风险因素，并确定最能预测认知老化的特定健康风险因素（使用以前未使用的多变量遗传模型）; 5）检查与认知老化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，将双胞胎方法与解析认知组件过程的实验/神经科学方法相结合，并使用具有成本效益的心理生理学方法（瞳孔测量）来测量认知努力。公共卫生相关性：VETSA 2建立在VETSA 1的独特资源基础上，为研究从中年（研究不足的领域）到老年早期的变化，以及了解生物和环境因素的相互作用创造了宝贵的资源，这些因素是衰老或成功衰老的关键早期预测因素。VETSA 2项目建立在VETSA 1的独特资源基础上，为中年研究（一个研究不足的领域）和了解生物和环境因素的相互作用创造了宝贵的资源，这些因素是成功老龄化的关键决定因素。

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.