The VETSA Longitudinal Twin Study of Cognition and Aging (VETSA 4)

VETSA 认知与衰老纵向孪生研究 (VETSA 4)

• 批准号: 10163109
• 负责人: CAROL Elaine FRANZ
• 金额: $ 383.29万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10163109
• 关键词: Accounting; Address; Adult; Age; Age-Years; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein; Anxiety; Binding; Biological Assay; Biological Markers; Biometry; Blood; Cardiovascular Diseases; Classification; Cognition; Cognitive; Communities; Consensus; Data; Dementia; Detection; Diagnosis; Digit structure; Disease; Disease Progression; Early identification; Elderly; Environment; Episodic memory; Etiology; Family; Funding; Genetic; Genetic Crosses; Genotype; Growth; Health; Heritability; Hour; Impaired cognition; Individual; Individual Differences; Knowledge; Lead; Light; Malignant Neoplasms; Measures; Mediator of activation protein; Medical; Medical History; Memory; Mendelian randomization; Meta-Analysis; Modeling; Mydriasis; Nerve Degeneration; Participant; Pathologic; Pattern; Phase; Plasma; Positioning Attribute; Process; Public Health; Pupil; Quality of life; Questionnaires; Research; Resources; Risk; Risk Factors; Sampling; Savings; Short-Term Memory; Staging; System; Telephone; Testing; Time; Twin Multiple Birth; Twin Studies; United States National Institutes of Health; Update; Vietnam; Visit; Visual; Work; age related; base; causal model; cognitive ability; cognitive change; cognitive function; cognitive performance; cognitive process; cognitive reserve; cognitive testing; cost; design; executive function; familial Alzheimer disease; genome-wide; improved; indexing; memory recall; middle age; mild cognitive impairment; neurofilament; non-demented; novel; polygenic risk score; pre-clinical; predictive marker; prevent; protective factors; psychosocial; response; tau Proteins; virtual

PROJECT SUMMARY/ABSTRACT Alzheimer's disease (AD) is the most costly and burdensome disease in the U.S. Its public health impact will only grow with the increase of 65-75 year olds in the next decade. The AD process begins 2 or more decades before dementia onset. Identifying individuals during early stages (e.g., mild cognitive impairment ([MCI]) is estimated to result in massive savings. Thus, NIH and Alzheimer's Association consensus statements emphasize early identification. Like cardiovascular disease, focusing on middle age is crucial for earlier identification of risk for cognitive decline, preclinical AD, and MCI. Despite this protracted progression of AD pathology, little is known about its temporal course and relation to cognition in middle age. To address this critical knowledge gap, we propose to collect a fourth wave of data in the Vietnam Era Twin Study of Aging (VETSA). VETSA provides detailed characterization of change throughout midlife. With wave 4, VETSA will cover an 18-year period in our community-dwelling sample. VETSA began with virtually all subjects in their 50s, so we can track shifts from normal cognition to MCI/AD and normal to abnormal biomarker status. We focus on 4 sets of indicators that improve the ability to identify at-risk individuals earlier than in most studies: 1) extensive cognitive testing; 2) plasma AD biomarkers for beta-amyloid (Aβ), tau, and neurofilament light (NfL); 3) polygenic risk scores; and 4) novel assessments of cognitive processes. Almost all subjects will have been Aβ- at VETSA 1. Average age at VETSA 4 will be 74, and a meta-analysis indicates that >30% of non- demented adults at age 75 are Aβ+. Thus, leveraging data from previous waves, the timing is ideal to capture the transition to disease states. We utilize the amyloid-tau-neurodegeneration (ATN) biomarker classification system and examine the proposed A→T→N staging of the AD continuum. Naturally, most research focuses on ATN biomarkers as predictors, but it would be highly advantageous to identify people at risk before reaching pathological Aβ levels. Thus, Aim1 will examine plasma ATN biomarker trajectories as well as predictors of ATN biomarker accumulation and abnormality. We have biomarker data from VETSA 1 and 3, and will perform assays on VETSA 4 data. Aim 2 models risk and protective factors for cognitive decline, biomarker trajectories, and progression to MCI using genetically-informative analyses that can test causality. With 4 time points, we will use our combination of twin and polygenic risk score data and our extensive health/medical and psychosocial data to elucidate factors accounting for accelerated cognitive decline. In Aim 3, we evaluate 2 novel early risk indicators by: a) extending our work on pupil dilation as a measure of cognitive effort before cognitive performance declines; and b) assessing visual short-term memory binding, an early indicator tested primarily in familial AD families. To increase detection of decline, Aim 4 adds telephone/mailed assessments partway in the funding period. Wave 4 will have N=1000. VETSA's unique features make it a most promising resource for advancing knowledge about early identification, with potential for a profound public health impact.

项目总结/摘要 阿尔茨海默病（AD）是美国最昂贵和负担最重的疾病。 在未来十年中，只会随着65-75奥尔兹的增加而增长。AD过程开始于20年或更长时间 在痴呆症发作之前。在早期阶段识别个体（例如，轻度认知障碍（MCI）是 估计可以节省大量费用。因此，NIH和阿尔茨海默氏症协会的共识声明 强调早期识别。就像心血管疾病一样，关注中年对早期预防至关重要。 识别认知能力下降、临床前AD和MCI的风险。尽管AD进展缓慢， 病理学，很少有人知道它的时间过程和关系，在中年认知。为了解决这个 关键的知识差距，我们建议收集第四波数据在越南时代双胞胎研究老化 （VETSA）. VETSA提供了整个中年变化的详细描述。第四波，VETSA将 在我们的社区住宅样本中覆盖了18年的时间。VETSA从几乎所有的科目开始， 50秒，因此我们可以跟踪从正常认知到MCI/AD以及从正常到异常生物标志物状态的变化。我们 重点关注4组指标，这些指标提高了比大多数研究更早识别风险个体的能力： 1)广泛的认知测试; 2）β-淀粉样蛋白（Aβ）、tau和神经丝光的血浆AD生物标志物 (NfL)3）多基因风险评分; 4）认知过程的新评估。几乎所有的科目都有 在VETSA 1中为Aβ-。VETSA 4的平均年龄为74岁，荟萃分析表明，>30%的非 75岁的痴呆成年人为Aβ+。因此，利用前几波的数据， 向疾病状态的转变。我们利用淀粉样蛋白-tau-神经变性（ATN）生物标志物分类 系统，并检查提出的AD连续体的A→T→N分期。当然，大多数研究都集中在 ATN生物标志物作为预测因子，但在达到之前确定处于风险中的人是非常有利的。 病理性Aβ水平。因此，Aim 1将检查血浆ATN生物标志物轨迹以及 ATN生物标志物积累和异常。我们有来自VETSA 1和3的生物标志物数据， VETSA 4数据的分析。目标2模型认知能力下降的风险和保护因素，生物标志物 轨迹，并使用遗传信息分析，可以测试因果关系进展到MCI。4时间 点，我们将使用我们的双胞胎和多基因风险评分数据和我们广泛的健康/医疗和 社会心理数据，以阐明加速认知衰退的因素。在目标3中，我们评估2 新的早期风险指标：a）扩展我们对瞳孔扩张的工作，作为之前认知努力的衡量标准 认知能力下降;和B）评估视觉短期记忆结合，这是测试的早期指标 主要是家族性AD。为了增加对下降的检测，Aim 4增加了电话/邮件评估 在融资期的中途。第4波将具有N=1000。VETSA的独特功能使其成为最有前途的 这是一个促进早期识别知识的资源，有可能产生深远的公共卫生影响。