Stress Mental Disorders Accelerated Aging and Dementia a 35 year Cohort Study

压力性精神障碍加速衰老和痴呆症 35 年队列研究

基本信息

批准号：
9930377
负责人：
WILLIAM W EATON
金额：
$ 34.79万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9930377
关键词：
Address African American Age Factors Age-Years Aging Alzheimer&apos s Disease Alzheimer&apos s disease risk Alzheimer’s disease biomarker Anxiety Disorders Baltimore Biological Markers Blood C-reactive protein CDKN2A gene Candidate Disease Gene Cardiovascular Diseases Catchment Area Cell Aging Chronic Cognition Cognitive Cohort Studies Cross-Sectional Studies Data Data Collection Dementia Depressive disorder Detection Diabetes Mellitus Diagnosis Diagnostic Disease Elderly Epidemiology Epigenetic Process Event Exposure to Financial cost Follow-Up Studies Gene-Modified Genes Genetic Goals Growth Health Home environment Impaired cognition Inflammation Inflammatory Interleukin-6 Interview Knowledge Lead Length Life Link Longitudinal Studies Measures Mediating Mediator of activation protein Medical Mental Depression Mental disorders Meta-Analysis Methodology Methylation Modification Mood Disorders Morbidity - disease rate Neuropsychological Tests Older Population Outcome Participant Patient Self-Report Prospective Studies Psychological Stress Recording of previous events Research Risk Risk Factors Sampling Site Sleep Sleep disturbances Stress Stressful Event Structure Survivors TNF gene Telomere Shortening Testing Trauma Validity and Reliability Wrist actigraphy adjudicate age related aged aging population anxiety symptoms associated symptom base cohort depressive symptoms disability disability burden follow-up functional decline functional disability functional outcomes genome wide association study genome-wide life history middle age mild cognitive impairment modifiable risk novel outcome prediction population based prevent risk variant senescence sleep abnormalities sleep onset stressor telomere trauma exposure

项目摘要

Numerous studies demonstrate links between depressive symptoms or disorders and poor cognitive and functional outcomes. Anxiety symptoms and disorders, poor sleep, and stressful life events are common and correlated with depression, but little is known about their association with cognitive and functional decline, such as occurs in Alzheimer's disease (AD). These stress-related exposures are also associated with medical morbidity and disability, but the mechanisms linking them to poor health outcomes are unclear. Cross-sectional studies suggest that these exposures might lead to these outcomes by hastening cellular aging, measured by shortening of telomeres. Prospective studies in cohorts with well-characterized histories of stress-related exposures and repeated measures of cellular aging are needed to investigate this possibility. We propose to analyze these issues using data already collected in the Baltimore Epidemiologic Catchment Area (ECA) Followup Study cohort, adding another wave of data collection. The Baltimore ECA Study began collecting structured diagnostic interview data on depressive and anxiety disorders in 1981 in a representative sample of East Baltimore residents, and did so over three additional waves, most recently in 2004 (Wave 4). In addition to measures of anxiety and depressive symptoms and disorders, the diverse (35% African American) ECA cohort has completed repeated measures of poor sleep, life stressors, trauma exposure, cognition, and functional impairment. In 2004, when all participants were aged ≥40 years, they donated blood and buccal samples. All ECA subjects are now aged ≥50 (estimated mean = 68, range 52-96). We will locate and interview an estimated 601 participants from Wave 4, repeating structured diagnostic interview assessment of mental disorders, and measuring life stressors, trauma exposure, and poor sleep by both self-report and wrist actigraphy. Participants will complete neuropsychological tests and functional measures, and will again donate blood and buccal samples. This will enable us to determine the association of 35-year histories of stress- related exposures, from mid to later life, with cognitive and functional decline, adjudicated mild cognitive impairment and dementia diagnoses, including probable and possible AD, and biomarkers of cellular aging: shortening of telomeres and increases in p16ink4a levels from 2004 to 2016. We will also determine if these exposures are associated with epigenetic modification of genes in the ECA that we select based on novel genome-wide association and methylation analyses we will conduct in existing data from the Baltimore Longitudinal Study of Aging (BLSA) and the InCHIANTI cohorts. We will examine whether methylation of these candidate sites, and measures of inflammation (measured in blood in 2004 and 2016) in the ECA, mediate hypothesized predictive associations in the ECA cohort. Results will clarify the link between stress-related exposures from mid to later life and aging-related outcomes, advance knowledge of mechanisms linking these exposures to disease and disability, and provide clues to avenues for preventing these outcomes.

大量研究表明，抑郁症状或疾病与认知不良和功能结果。焦虑症状和疾病，睡眠不良和压力性生活事件很常见，并且与抑郁症相关，但对它们与认知和功能下降的关联知之甚少，如阿尔茨海默氏病（AD）所发生的。这些与压力有关的暴露也与医疗有关发病率和残疾，但是将它们与健康不良结局联系起来的机制尚不清楚。横截面研究表明，这些暴露可能通过加速细胞衰老，通过端粒缩短。与应力有关需要进行暴露和重复测量细胞衰老以研究这种可能性。我们建议使用在巴尔的摩流行病学流域（ECA）中收集的数据分析这些问题后续研究队列，增加了一波数据收集。巴尔的摩ECA研究开始收集 1981年在代表性样本中，有关抑郁和焦虑症的结构化诊断访谈数据东巴尔的摩居民，并在2004年的额外三波（第4波）中进行了三波。此外为了衡量焦虑和抑郁症状和疾病，潜水员（35％的非裔美国人）ECA 队列已经完成了睡眠不良，生活压力，创伤暴露，认知和功能障碍。 2004年，当所有参与者年龄≥40岁时，他们捐赠了血液和颊样品。所有ECA受试者现在年龄≥50岁（估计平均值= 68，范围52-96）。我们将找到和面试估计来自第4波的601名参与者，重复对心理的结构化诊断访谈评估自我报告和手腕的疾病，测量生活压力，创伤暴露和睡眠不佳摄影。参与者将完成神经心理学测试和功能测量，并将再次捐赠血液和颊样品。这将使我们能够确定应力的35年历史的关联从中期到以后的相关暴露，认知和功能下降，调整了轻度认知损伤和痴呆诊断，包括有问题和可能的AD，以及细胞衰老的生物标志物：从2004年到2016年缩短端粒和P16INK4A水平的增加。我们还将确定这些是否是否暴露与我们基于新颖的ECA中基因的表观遗传修饰有关全基因组的关联和甲基化分析我们将在巴尔的摩的现有数据中进行老化（BLSA）和Inchianti队列的纵向研究。我们将检查是否甲基化 ECA中的候选部位和炎症的测量（2004年和2016年的血液测量）介导 ECA队列中假设的预测关联。结果将阐明与压力相关的联系从中期到以后的生活和与衰老有关的结果的暴露，提前了解与这些联系的机制暴露于疾病和残疾，并为预防这些结果的途径提供线索。