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)

• 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
• 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' 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

 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（由适用提供）：早期识别和治疗危险因素的进展可能是反对阿尔茨海默氏病（AD）和与年龄相关的认知能力下降的主要武器，就像是用于心血管疾病和癌症一样。对于AD而言，直到最近，研究人员得出的结论是，治疗无效的可能原因是该疾病过程在痴呆发作前发生。 AD从1990年的第32级疾病中跃升至2010年的第9位（任何疾病的增长最大），从17日到12日，与疾病的生活相比，与心血管疾病或癌症的显着改善相比，强调了危险因素的早期识别和治疗。有了这些令人震惊的趋势，也就不足为奇了，现在有更强大的推动AD和认知障碍。因此，我们的重点是轻度认知障碍（MCI），这可能是AD的先驱。在痴呆症之前几十年开始的疾病过程还要求关注中年和从中年到老年的过渡。但是，这个时期仍然值得注意。我们建议在越南时代的衰老研究（VETSA）中收集第三波数据。 Vetsa的10岁年龄群狭窄，可以评估人身内部差异。来自55岁和61岁的平均年龄3个年龄3个数据的数据将为早期识别MCI提供12年的随访。目的1是使用基于纵向一致性的最新方法，转换为MCI的人比例恢复正常的最大有效MCI定义，以及与生物标志物的关联。我们将包括3种具有筛查大量人群的生物标志物：血液基（Aß，外泌体P-TAU，簇，ApoE，NT-Probnp，crp，crp，免费睾丸激素）； AD和认知障碍的外部验证多基因风险评分；和物理（瞳孔测定，光反射，勃起功能障碍，代谢综合征）。前两个类别是该提案的新事物。利用Vetsa 1存储的等离子体，我们将检查Vetsa 1和3的血液生物标志物。AIM 2是基于生物标志物和传统风险因素的组合，专门针对MCI开发第一个风险指数，以最大程度地提高敏感性和特异性。目的3是阐明连续测量的认知功能和认知变化的异质性，并识别预测因素和相关性。在这样做的过程中，我们将确定不同的变化子组 模式以及认知变化对特定环境环境的差异敏感性，具体取决于遗传因素。目标4是确定认知弹性的预测因素（对多基因或血液的危险因素高，但没有认知障碍），以便我们可以了解成功的认知衰老和下降。我们将有1261个带有波3数据的双胞胎。完成后，我们将使数据公开可供研究。我们独特的功能组合使Vetsa在曲线方面取得了有关早期识别和可修改风险因素的知识的能力，这些因素可能会产生深远的公共健康影响。