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; 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（由适用提供）：大量研究表明，抑郁症状或疾病与认知和功能效果差之间的联系。焦虑症状和疾病，睡眠不佳和压力性生活事件很常见，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。这些与压力相关的暴露也与医疗发病率和残疾有关，但是将它们与不良健康结果联系起来的机制尚不清楚。横断面研究表明，这些暴露可能通过缩短端粒来衡量的细胞衰老，从而导致这些结果。我们建议使用已经在巴尔的摩流行病学流域（ECA）后续研究同位研究中收集到的数据来分析这些问题的人群中的前瞻性研究，并重复进行了与压力相关的暴露和重复测量细胞衰老的测量。巴尔的摩ECA的研究开始在1981年在东巴尔的摩居民的代表性样本中收集有关抑郁和焦虑症的结构化诊断访谈数据，并在2004年的额外三波（第4波）中进行了三波。除了焦虑和抑郁症状和疾病的措施外，潜水员（35％的非裔美国人）ECA队列还完成了睡眠不良，生命压力，创伤，认知和功能障碍的重复测量。 2004年，当所有参与者均年龄≥40岁时，他们捐赠了血液和颊样本。所有ECA受试者现在年龄≥50岁（估计平均值= 68，范围52-96）。我们将在第4波中找到和访谈估计有601名参与者，重复对精神障碍的结构化诊断访谈评估，并通过自我报告和手腕行为摄影来测量生活压力，创伤和睡眠不佳。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本。这将使我们能够确定与压力相关的暴露历史的关联，从中期到以后的生活，以及认知和功能下降，调整了轻度的认知障碍和痴呆诊断，包括有问题的和可能的AD，包括细胞老化的生物标志物，以及在2004年的p16ink4a exportion shipertive and eccient in 2004 tecig necig necig night of 2004 deL the If the If the 2016。我们根据新型基因组关联和甲基化分析选择的ECA中的基因将在巴尔的摩衰老纵向研究（BLSA）和Inchianti同类群中进行的现有数据中进行。我们将检查这些候选部位的甲基化以及ECA中的炎症测量（在2004年和2016年的血液中测量），培养基在ECA队列中假设了预测性的相关性。结果将阐明与压力相关的暴露之间的联系，从中期到以后的生活与与衰老有关的结果，提高有关将这些暴露与疾病和残疾联系起来的机制的知识，并为防止这些结果提供了线索。