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

• 批准号: 9344528
• 负责人: WILLIAM W EATON
• 金额: $ 80.74万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 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/9344528
• 关键词: Address; African American; Age Factors; Age-Years; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; 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; 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; functional decline; functional disability; functional outcomes; genome wide association study; genome-wide; life history; mild cognitive impairment; modifiable risk; novel; outcome prediction; population based; prevent; public health relevance; risk variant; senescence; sleep abnormalities; sleep onset; stressor; telomere

 DESCRIPTION (provided by applicant): 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 cognitie 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.

 描述（由申请人提供）：大量研究表明抑郁症状或障碍与认知和功能不良之间存在联系。焦虑症状和障碍、睡眠不佳以及生活压力事件很常见，并且与抑郁症相关，但人们对它们与抑郁症的关系知之甚少。认知和功能下降，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发病率和残疾有关，但将它们与不良健康结果联系起来的机制尚不清楚，这些暴露可能会加速导致这些结果。细胞衰老，通过端粒缩短来测量，需要对具有明确的压力相关暴露史的队列进行前瞻性研究，并重复测量细胞衰老，以研究这种可能性。巴尔的摩流行病学流域 (ECA) 随访研究队列，增加了另一波数据收集 巴尔的摩 ECA 研究于 1981 年开始在东巴尔的摩居民的代表性样本中收集有关抑郁症和焦虑症的结构化诊断访谈数据，并在另外三个项目中进行了收集。波，最近一次是在 2004 年（第 4 波） 除了对焦虑和抑郁症状和障碍的测量外，多样化的（35% 非洲裔美国人）ECA 队列还完成了对睡眠不良、生活质量的重复测量。 2004 年，当所有参与者年龄≥40 岁时，所有 ECA 受试者现在年龄≥50 岁（估计平均值 = 68，范围 52-96）。我们将找到并采访第 4 波中的约 601 名参与者，重复对精神障碍进行结构化诊断访谈评估，并通过自我报告和腕带测量生活压力源、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，并再次捐献血液和口腔样本，这将使我们能够确定从中年到晚年的 35 年压力相关暴露史与认知和功能衰退之间的关系。 ，裁定轻度认知障碍和痴呆症诊断，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，端粒缩短和 p16ink4a 水平增加。我们还将确定这些暴露是否与 ECA 中基因的表观遗传修饰相关，我们将根据巴尔的摩纵向衰老研究 (BLSA) 和 InCHIANTI 队列的现有数据进行新的全基因组关联和甲基化分析。我们将检查 ECA 中这些候选位点的甲基化和炎症测量（2004 年和 2016 年在血液中测量）是否介导了 ECA 结果中渴望的预测关联。将阐明从中年到晚年与压力相关的暴露与衰老相关结果之间的联系，增进对这些暴露与疾病和残疾之间联系的机制的了解，并为预防这些结果的途径提供线索。