The VETSA Longitudinal Twin Study of Cognition and Aging (VETSA 3)

VETSA 认知与衰老纵向孪生研究 (VETSA 3)

基本信息

批准号：
9283301
负责人：
WILLIAM S. KREMEN
金额：
$ 215.33万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9283301
关键词：
Address Age Age-Years Age-associated memory impairment Aging Alzheimer&apos s Disease Amyloid beta-Protein Archives Biological Assay Biological Markers Biometry Blood Blood Pressure Cardiovascular Diseases Categories Classification Clinical Cognition Cognitive Cognitive aging Consensus Data Dementia Detection Diagnosis Disease Early Diagnosis Early identification Early treatment Education Environment Erectile dysfunction Genes Genetic Genotype Growth Heterogeneity Hypertension Impaired cognition Impairment Individual Individual Differences Knowledge Light Malignant Neoplasms Measures Metabolic syndrome Modeling Obesity Outcome Pathologic Pattern Persons Phase Phenotype Physical activity Physiological Plasma Population Positioning Attribute Prevention Process Psyche structure Psychosocial Factor Public Health Quality of life Reflex action Research Research Personnel Resources Risk Risk Factors Sampling Sensitivity and Specificity Stress Subgroup Sum Techniques Testing Testosterone Twin Multiple Birth Twin Studies Variant Vietnam aging population base biomarker identification blood-based biomarker cognitive change cognitive function cognitive reserve cohort design follow-up gene environment interaction genome wide association study hypercholesterolemia improved indexing ineffective therapies insight middle age mild cognitive impairment modifiable risk pro-brain natriuretic peptide (1-76)psychosocial public health relevance public health research resilience screening sulfated glycoprotein 2 tau Proteins trend virtual weapons years lived with disability years of life lost

项目摘要

DESCRIPTION (provided by applicant): Advances in early identification and treatment of risk factors are likely to be major weapons in the battle against Alzheimer's disease (AD) and age-related cognitive decline, just as they are for cardiovascular disease and cancer. For AD, it is only relatively recently that researchers concluded that a likely reason for treatment ineffectiveness is the fact that the disease process unfolds decades before dementia onset. AD jumped from the 32nd ranked disease for years of life lost in 1990 to 9th in 2010 (largest increase of any disease), and from 17th to 12th for years lived with disability, in contrast to substantial improvements in cardiovascular disease or cancer where early identification and treatment of risk factors are emphasized. With these alarming trends, it is no wonder that there is now an ever stronger push for earlier identification of AD and cognitive impairment. Therefore, our focus is on mild cognitive impairment (MCI), which can be a precursor to AD. A disease process beginning decades before dementia also calls for a focus on midlife and the transition from middle age to early old age. However, this age period remains notably understudied. We propose to collect a third wave of data in the Vietnam Era Twin Study of Aging (VETSA). VETSA has a narrow 10-year age cohort for assessing within-person differences. Data from mean ages 55 and 61 plus wave 3 data at age 67 will provide a 12-year follow-up for early identification of MCI. Aim 1 is to construct a maximally valid MCI definition using a state-of-the-art approach based on longitudinal consistency, proportion of people converting to MCI and reverting to normal, and associations with biomarkers. We will include 3 categories of biomarkers with potential for screening large populations: blood-based (Aß, exosomal p-tau, clusterin, APOE, NT-proBNP, CRP, free testosterone); externally-validated polygenic risk scores for AD and cognitive impairment; and physiological (pupillometry, light reflex, erectile dysfunction, metabolic syndrome). The first 2 categories are new to this proposal. Capitalizing on plasma stored from VETSA 1, we will examine blood-based biomarkers from VETSA 1 and 3. Aim 2 is to develop the first risk index specifically for MCI based on the combination of biomarkers and traditional risk factors that maximizes sensitivity and specificity. Aim 3 is to elucidate the heterogeneity of continuously measured cognitive function and cognitive change, and identify predictors and correlates. In doing so, we will identify different subgroups of change patterns, and differential sensitivity of cognitive change to particular environmental contexts depending on genetic factors. Aim 4 is to determine predictors of cognitive resilience (being high on polygenic or blood-based risk factors but having no cognitive impairment), so that we can be informative about successful cognitive aging as well as decline. We will have 1261 twins with wave 3 data. After completion, we will make the data publicly available for research. Our unique combination of features puts VETSA ahead of curve with respect to its ability to gain knowledge about early identification and modifiable risk factors that can have a profound public health impact.

描述（由申请人提供）：危险因素的早期识别和治疗方面的进步可能成为对抗阿尔茨海默病（AD）和与年龄相关的认知能力下降的主要武器，就像对抗心血管疾病和癌症一样。直到最近，研究人员才得出结论，治疗无效的一个可能原因是，AD 发病早于 1990 年，AD 从 1990 年排名第 32 位的疾病跃升至第 9 位。 2010 年（所有疾病中增幅最大），残疾年数从第 17 位增加到第 12 位，而心血管疾病或癌症的显着改善则强调早期识别和治疗危险因素，这些令人担忧的趋势也就不足为奇了。现在人们越来越强烈地推动早期识别 AD 和认知障碍，因此，我们的重点是轻度认知障碍 (MCI)，它可能是 AD 的先兆，也是一种早于痴呆症数十年就开始的疾病过程，也需要重点关注。关于中年和然而，我们建议在越南时代双胞胎老龄化研究 (VETSA) 中收集第三波数据以进行评估。平均年龄 55 岁和 61 岁的数据加上 67 岁的第 3 波数据将为 MCI 的早期识别提供 12 年的随访，目标 1 是构建最有效的 MCI 定义。使用基于纵向一致性、转为 MCI 并恢复正常的人数比例以及与生物标记物的关联的最先进方法，我们将包括 3 类具有筛查大量人群潜力的生物标记物：基于血液的 (Aß)。、外泌体 p-tau、簇蛋白、APOE、NT-proBNP、CRP、游离睾酮）；经过外部验证的 AD 和认知障碍多基因风险评分（瞳孔测量、光反射、前 2 类是该提案中的新类别，我们将利用 VETSA 1 储存的血浆检查 VETSA 1 和 3 中的血液生物标志物。目标 2 是专门针对 MCI 开发第一个风险指数。基于生物标志物和传统风险因素的结合，最大化敏感性和特异性，目标 3 是阐明连续测量的认知功能和认知变化的异质性，并确定预测因子和相关性。因此，我们将确定不同的变革子组目标 4 是确定认知弹性的预测因素（多基因或基于血液的风险因素较高，但没有认知障碍），以便我们能够提供信息。完成后，我们将公开这些数据以供研究，从而使 VETSA 在获取知识的能力方面处于领先地位。关于早期识别和可对公共卫生产生深远影响的可改变的风险因素。