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: 9516868
• 负责人: WILLIAM W EATON
• 金额: $ 55.25万
• 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/9516868
• 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; middle age; mild cognitive impairment; modifiable risk; novel; outcome prediction; population based; prevent; public health relevance; risk variant; senescence; sleep abnormalities; sleep onset; stressor; telomere; trauma exposure

 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.