Colorado Adoption/Twin Study of Lifespan behavioral development & cognitive aging (CATSLife2)

科罗拉多州收养/双胞胎终身行为发展研究

• 批准号: 10432073
• 负责人: CHANDRA A REYNOLDS
• 金额: $ 235.72万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10432073
• 关键词: Accounting; Address; Adolescence; Adolescent; Adoption; Adult; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Behavioral; Biological Markers; Blood; Body mass index; Buffers; Child; Cognition; Cognitive; Cognitive aging; Colorado; DNA Methylation; Data; Data Collection; Dementia; Development; Disadvantaged; England; Environment; Environmental Risk Factor; Epigenetic Process; Etiology; Exposure to; Follow-Up Studies; Foundations; Genes; Genetic; Genetic Risk; Genotype; Health; Health Services; Health behavior; Health education; Heritability; Human Herpesvirus 4; Immune; Individual; Individual Differences; Inflammatory; Life; Life Style; Light; Longevity; Maintenance; Measures; Mediating; Mediator of activation protein; Methylation; Modeling; Neighborhoods; Neurotransmitters; Participant; Pathway interactions; Pattern; Performance; Positioning Attribute; Predictive Factor; Prevention; Risk; Risk Factors; Siblings; Signal Transduction; Site; Sleep; Speed; Stress; Testing; Twin Multiple Birth; Twin Studies; Wales; Work; apolipoprotein E-4; cognitive ability; cognitive change; cognitive development; cognitive function; cognitive performance; cognitive reserve; contextual factors; cytokine; design; follow-up; genome-wide; improved; indexing; infancy; microbial; middle age; neurofilament; physical conditioning; predictive marker; proband; prospective; protective factors; resilience; sociodemographics; substance use; transcriptome; walkability; young adult

Emerging evidence suggests that individual differences in cognitive aging unfold across a lifetime; however, relatively little is known as to how early life versus proximal influences accumulate to impact cognitive functioning across midlife. The Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife) seeks a greater understanding of the environmental and genetic factors that drive increasing divergence in cognitive maintenance. CATSLife comprises the prospective Colorado Adoption Project (CAP) and parallel Longitudinal Twin Study (LTS), now tested at ages 28-45 years (CATSLife1). We propose a 5-year follow-up of 1400 adoptive and nonadoptive probands, siblings, and twins as they navigate the transition to midlife at ages 33-50 years (CATSLife2). Whereas CATSLife1 established baseline performance as participants prepare for transitions to midlife, CATSLife2 proposes to evaluate stability and change across the midlife transition. Further, we propose to integrate the prospective Twins Early Development Study (TEDS) with a new assessment of 5000 twins at age 28 years, allowing us to build on over 20 years of prior data collection, including genome-wide genotyping, to explore similar predictors of cognitive maintenance. As participants transition to midlife, we will leverage powerful design features and a wealth of prospective data collected from infancy through adulthood, including a full adoption design, to examine causal implications of early environmental risk and protective factors, and a twin design to examine environmental factors that may have causal influence on cognition, controlling for familial confounds. As we leverage data from prior assessments with CATSLife1, the opportunity to investigate the transition across midlife with CATSLife2 is ideal. We will use our twin/adoption design with polygenic score data (PGS), detailed cognitive batteries, physical health, proposed biomarkers of accelerated aging that may participate in immune- inflammatory and neurotransmitter pathways, and neighborhood features to shed light on risk-resilience factors that account for midlife cognitive stability and change. This integrated follow-up study of CATSLife and TEDS aims to: 1) Evaluate individual differences in stability and change of cognitive abilities in midlife, considering cognitive reserve pathways vis-a-vis genetic and genetically mediated environmental influences; 2) Evaluate genetic factors with lifestyle and health behaviors that predict cognitive stability and change, considering early life reserve and genetic moderation; 3) Evaluate biomarkers of accelerated aging as predictors and mediators of cognitive stability and change, uniquely characterizing biomarker patterns and change at the midlife transition; and 4) Evaluate stressful and buffering contextual factors that predict cognitive stability and change, addressing individual socio-demographics and neighborhood features, accounting for active (rGE) selection. The findings from this proposed CATSLife/TEDS follow-up study could substantially increase our understanding of the genetic and environmental etiologies of individual differences in cognitive aging.

新出现的证据表明，认知老化的个体差异贯穿一生;然而， 对于早期生活与近端影响如何积累以影响认知能力， 在中年时期发挥作用科罗拉多收养/双生子终生行为发展研究 认知老化（CATSLife）寻求更好地了解环境和遗传因素， 认知维持的差异越来越大。CATSLife包括预期的科罗拉多收养 项目（CAP）和平行的纵向双胞胎研究（LTS），现在在28-45岁（CATSLife 1）进行测试。我们 建议对1400名收养和非收养先证者、兄弟姐妹和双胞胎进行为期5年的随访， 33-50岁的中年过渡（CATSLife 2）。CATSLife 1建立了基线， 作为参与者准备过渡到中年的表现，CATSLife 2建议评估稳定性， 在中年过渡期的变化。此外，我们建议尽早整合未来的双胞胎 发展研究（TEDS），对5000对28岁的双胞胎进行了新的评估，使我们能够建立在 20年的既往数据收集，包括全基因组基因分型，以探索认知功能障碍的相似预测因素。 上维护随着参与者过渡到中年，我们将利用强大的设计功能和丰富的 从婴儿期到成年期收集的前瞻性数据，包括完整的收养设计，以检查因果关系， 早期环境风险和保护因素的影响，以及一个双胞胎设计，以检查环境 可能对认知有因果影响的因素，控制家族性混淆。当我们利用数据 从以前的评估与CATSLife 1，有机会调查过渡到中年与 CatsLife 2是理想的。我们将使用我们的双胞胎/收养设计与多基因评分数据（PGS），详细的认知 电池，身体健康，提出的加速老化的生物标志物，可能参与免疫- 炎症和神经递质通路，以及揭示风险弹性因素的邻近特征 中年认知稳定和变化的原因CATSLife和TEDS的综合随访研究 目的：1）评估中年认知能力的稳定性和变化的个体差异，考虑 认知储备途径与遗传和遗传介导的环境影响; 2）评估 遗传因素与生活方式和健康行为，预测认知稳定性和变化，考虑早期 生命储备和遗传调节; 3）评估加速老化的生物标志物作为预测因子和介质 认知稳定性和变化，独特地表征生物标志物模式和中年变化 过渡;以及4）评估预测认知稳定性和变化的压力和缓冲背景因素， 解决个人社会人口统计和邻里特征，占主动（rGE）选择。 这项拟议的CATSLife/TEDS后续研究的结果可能会大大增加我们的 了解认知老化中个体差异的遗传和环境病因。