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(申请人提供)：风险因素的早期识别和治疗的进展很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，就像它们对心血管疾病和癌症一样。对于AD，研究人员直到最近才得出结论，治疗无效的一个可能原因是疾病过程在痴呆症发作前几十年就开始了。AD从1990年的第32位上升到2010年的第9位(是所有疾病中增幅最大的)，残疾患者从第17位上升到第12位，这与心血管疾病或癌症的显著改善形成对比，后者强调早期识别和治疗风险因素。有了这些令人震惊的趋势，难怪现在有越来越强烈的推动，要求更早地识别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的先兆。在痴呆症之前几十年就开始的疾病过程也需要关注中年和从中年到早年的过渡。然而，对这一年龄段的研究仍然明显不足。我们建议在越南时代的双胞胎老龄化研究(VETSA)中收集第三波数据。Vetsa有一个狭窄的10岁年龄组来评估人与人之间的差异。来自平均年龄55岁和61岁的数据，加上67岁时的第3波数据，将为早期识别MCI提供12年的随访。目标1是使用最先进的方法构建一个最有效的MCI定义，该方法基于纵向一致性、转换为MCI和恢复正常的人的比例以及与生物标志物的关联。我们将包括3类具有筛查大量人群潜力的生物标志物：基于血液的(Aü、外体p-tau、Clusterin、APOE、NT-proBNP、CRP、游离睾酮)；外部验证的AD和认知障碍的多基因风险评分；以及生理的(瞳孔测量、光反射、勃起功能障碍、代谢综合征)。前两个类别是本提案中的新类别。利用Vetsa 1储存的血浆，我们将检测Vetsa 1和Vetsa 3的血液生物标记物。目标2是开发第一个专门针对MCI的风险指数，基于生物标记物和传统危险因素的组合，最大限度地提高敏感性和特异性。目的3是阐明持续测量的认知功能和认知变化的异质性，并确定预测因素和相关因素。在这样做的过程中，我们将确定变化的不同子组 模式，以及认知变化对特定环境背景的不同敏感性取决于遗传因素。目标4是确定认知韧性的预测因素(多基因或基于血液的风险因素较高，但没有认知障碍)，以便我们能够对成功的认知老化和衰退提供信息。我们将有1261对双胞胎和第3波数据。完成后，我们将公开这些数据供研究使用。我们独特的功能组合使Vetsa走在了曲线的前面，因为它有能力获得关于早期识别和可修改的风险因素的知识，这些因素可能会对公共健康产生深远的影响。