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能力差和认知能力差之间存在联系。焦虑症状和障碍、睡眠不佳和生活压力事件很常见。与抑郁症相关，但人们对它们与认知和功能下降的关系知之甚少，例如正如阿尔茨海默病 (AD) 中所发生的那样，这些与压力相关的暴露也与医疗有关。发病率和残疾，但将它们与不良健康结果联系起来的机制尚不清楚。研究表明，这些暴露可能通过加速细胞衰老而导致这些结果，通过测量对具有明确的压力相关史的队列进行前瞻性研究。我们建议需要对细胞老化进行暴露和重复测量来研究这种可能性。使用巴尔的摩流行病学集水区 (ECA) 已收集的数据分析这些问题后续研究队列，增加了另一波数据收集，巴尔的摩 ECA 研究开始收集。 1981 年抑郁症和焦虑症的结构化诊断访谈数据，代表性样本为东巴尔的摩居民，并在另外三波中这样做了，最近一次是在 2004 年（第四波）。根据焦虑和抑郁症状及障碍的衡量标准，多样化的 ECA（35% 为非裔美国人）队列已完成对睡眠不佳、生活压力源、创伤暴露、认知和 2004年，当所有参与者年龄≥40岁时，他们捐献了血液和颊部。所有 ECA 受试者年龄均≥ 50 岁（估计平均值 = 68，范围 52-96）。第 4 波估计有 601 名参与者，重复对心理健康进行结构化诊断访谈评估疾病，并通过自我报告和手腕测量生活压力源、创伤暴露和睡眠质量差参与者将完成神经心理学测试和功能测量，并将再次捐赠。这将使我们能够确定 35 年压力史之间的关联。从中年到晚年的相关暴露，伴随认知和功能下降，判定为轻度认知损伤和痴呆症诊断，包括可能和可能的 AD，以及细胞衰老的生物标志物：从 2004 年到 2016 年，端粒缩短，p16ink4a 水平增加。我们还将确定这些是否暴露与 ECA 中基因的表观遗传修饰有关，我们根据新的选择我们将在巴尔的摩的现有数据中进行全基因组关联和甲基化分析我们将研究衰老纵向研究 (BLSA) 和 InCHIANTI 队列是否存在甲基化。 ECA 中的候选部位和炎症测量（2004 年和 2016 年在血液中测量）介导 ECA 队列中的集中预测关联结果将阐明压力相关之间的联系。从中年到晚年的暴露和与衰老相关的结果，加深了对将这些联系起来的机制的了解暴露于疾病和残疾的情况，并提供预防这些结果的途径的线索。