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: 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
• 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' s Disease; Alzheimer' 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

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.

许多研究表明，抑郁症状或障碍与认知能力差和 功能性成果。焦虑症状和障碍，睡眠不好，以及紧张的生活事件是常见的， 与抑郁症有关，但对它们与认知和功能下降的关系知之甚少， 如阿尔茨海默病（AD）中发生的。这些与压力有关的暴露也与医疗有关。 这些疾病与健康状况不佳有关，但将其与健康状况不佳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而导致这些结果， 端粒缩短。在具有良好特征的应激相关病史的队列中进行的前瞻性研究 为了研究这种可能性，需要对细胞老化进行暴露和重复测量。我们建议 利用已经在巴尔的摩流行病学集水区（ECA）收集的数据分析这些问题 随访研究队列，增加另一波数据收集。巴尔的摩ECA研究开始收集 1981年，在一个有代表性的样本中， 东巴尔的摩居民，并在另外三波浪潮中这样做，最近一次是在2004年（第4波）。此外 焦虑和抑郁症状和障碍的措施，不同的（35%非洲裔美国人）ECA 队列完成了对睡眠不良、生活压力源、创伤暴露、认知和 功能障碍2004年，当所有参与者年龄≥40岁时，他们献血和颊粘膜， 样品所有ECA受试者的年龄均≥50岁（估计平均值= 68，范围52-96）。我们会找到并采访 来自第4波的估计601名参与者，重复结构化诊断访谈评估心理 疾病，并通过自我报告和腕关节测量生活压力源，创伤暴露和睡眠不良 活动记录仪参与者将完成神经心理学测试和功能测量，并将再次捐赠 血液和口腔样本我们就能确定35年的压力史- 从中年到晚年的相关暴露，伴认知和功能下降，判定为轻度认知 损伤和痴呆诊断，包括可能的和可能的AD，以及细胞衰老的生物标志物： 从2004年到2016年，端粒缩短和p16 ink 4a水平增加。我们还将确定这些 暴露与ECA中基因的表观遗传修饰有关，我们根据新的 我们将对来自巴尔的摩的现有数据进行全基因组关联和甲基化分析。 老龄化纵向研究（BLSA）和InChianti队列。我们将研究这些甲基化是否 候选位点，以及ECA中的炎症指标（2004年和2016年在血液中测量），介导 ECA队列中的假设预测关联。结果将阐明压力相关的 从中年到晚年的暴露和与衰老相关的结果，推进这些联系机制的知识 暴露于疾病和残疾，并提供线索的途径，以防止这些结果。