Earlier-Life Predictors of Midlife Risk Factors for Dementia: A 35-Year Follow-up

中年痴呆症风险因素的早期预测因素：35 年随访

• 批准号: 10596295
• 负责人: GEORGE W. REBOK
• 金额: $ 130.25万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10596295
• 关键词: Academic achievement; Address; Adult; Affect; African American; African American population; Age; Aging; Alcohols; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Attention; Baltimore; Behavior; Biological; Biological Markers; C-reactive protein; CDKN2A gene; Child; Childhood; Chronic stress; Cognition; Cognitive; Communities; Crime; Cyclin-Dependent Kinase Inhibitor; Data; Dementia; Diabetes Mellitus; Diagnosis; Drug usage; Early identification; Education; Elderly; Epigenetic Process; Exposure to; Future; Genetic; Genetic Materials; Health; Health protection; Home; Hyperlipidemia; Hypertension; Impaired cognition; Imprisonment; Individual; Inequity; Inflammation; Inflammatory; Interleukin-6; Intervention; Intervention Studies; Interview; Length; Life; Life Cycle Stages; Link; Measures; Mental disorders; Methylation; Modification; Not Hispanic or Latino; Obesity; Occupational; Outcome; Outcome Study; Participant; Pathway interactions; Physiological; Police; Poverty; Prevention; Prevention trial; Psychopathology; Public Health; Race; Risk; Risk Estimate; Risk Factors; Risk Marker; Role; Sampling; Sleep; Sleep disturbances; Social support; Stress; Subgroup; Symptoms; TNF gene; Trauma; Wrist; achievement test; actigraphy; cognitive performance; cohort; community violence; conduct problem; dementia risk; disorder risk; early life stress; first grade; follow-up; health disparity; inflammatory marker; middle age; modifiable risk; poor sleep; prevent; preventive intervention; prospective; protective factors; racial discrimination; racial disparity; risk variant; second grade; sex; stressor; substance use; telomere; traumatic event; universal prevention; young adult

Alzheimer’s disease (AD) and related dementias (AD/ADRD) are a public health crisis in the US marked by growing racial disparities, with African Americans (AAs) two to three times more likely to be diagnosed than non-Hispanic Whites. Efforts to identify modifiable earlier-life risk and protective factors for known midlife risk factors for poor cognitive outcomes in later life are needed to protect the health of middle-aged and older AAs. We propose to prospectively examine trajectories of stress exposures from childhood to early midlife as predictors of known midlife risk factors for subsequent AD/ADRD in two primarily (~66%) AA cohorts that are now ages 41-45 and have been followed repeatedly from age 6 to age 32 (2009-2011) by the Johns Hopkins Prevention Intervention Research Center (PIRC). Relevant individual- and community- level stress exposures that occur from early life to middle adulthood include: 1) adverse life circumstances (i.e., extreme poverty, residential instability, crime, incarceration, racial discrimination, traumatic events); 2) mental disorders and their symptoms; and 3) poor sleep (e.g., abnormal duration, fragmentation). Additionally, these stress exposures have been linked to other risk factors for AD/ADRD, including obesity, hypertension, and diabetes, by which AAs are disproportionately affected. We aim to determine the extent to which ~35-year trajectories of stress exposures are associated with estimated midlife risk for later-life AD/ADRD, physiological aging (telomere length, p16, methylation age), epigenetic modification, and inflammation, and cognitive performance—all measured in early midlife—and if these associations are moderated by sex, race, and AD/ADRD risk genes. We will also explore how the timing of exposures in the life-course affects these associations, and if other potential moderators (e.g., childhood academic achievement, educational/occupational attainment, alcohol/drug use, conduct problems, social support, perceived control) affect these associations. We will further explore effects of two early-life (ages 6-8) PIRC interventions on midlife study outcomes. To accomplish this, 1,150 PIRC participants will complete two in- home interviews including a cognitive battery and actigraphic sleep assessments, and we will collect biospecimens for genetic and epigenetic material and physiological aging measures. This study is a rare opportunity to clarify links of earlier-life stress exposures with estimated midlife dementia risk, identify vulnerable subgroups for targeted AD/ADRD prevention, elucidate the role of social inequities in determining racial disparities in AD dementia, and establish a midlife cognitive baseline for future follow-up of these unusually well-characterized longitudinal, primarily AA cohorts.

阿尔茨海默氏病（AD）和相关痴呆症（AD/ADRD）是美国的公共卫生危机 赛车分布正在不断发展，非洲裔美国人（AAS）被诊断的可能性是 非西班牙裔白人。努力确定已知中年的可修改的早期寿命风险和受保护因素 为了保护中年的健康和 年龄较大的AAS。我们建议前瞻性检查从童年到早期的压力暴露的轨迹 中年是已知的中年危险因素的预测因素 现在年龄在41-45岁的同伙，从6岁到32岁（2009- 2011年）反复遵循 约翰·霍普金斯预防干预研究中心（PIRC）。相关的个人和社区 - 从早期到成年中期发生的水平压力暴露包括：1）不利生活环境 （即极端贫困，居民的不稳定，犯罪，事件，种族歧视，创伤事件）； 2） 精神障碍及其症状； 3）睡眠不佳（例如，持续时间异常，碎片化）。 此外，这些压力暴露与AD/ADRD的其他风险因素有关，包括肥胖， 高血压和糖尿病，AA受到不成比例的影响。我们旨在确定程度 〜35年的压力暴露轨迹与估计的后期生活风险有关 AD/ADRD，身体衰老（端粒长度，p16，甲基化年龄），表观遗传修饰和 炎症和认知表现（都在中年早期测量），如果这些关联是 由性别，种族和AD/ADRD风险基因主持。我们还将探讨如何在 生命课会影响这些关联，以及其他潜在的主持人（例如，儿童学术 成就，教育/职业尝试，饮酒/毒品使用，进行问题，社会支持， 感知控制）影响这些关联。我们将进一步探索两个早期生命（6-8岁）PIRC的影响 中年研究结果的干预措施。为此，1,150名PIRC参与者将完成两个In- 家庭访谈在内 遗传和表观遗传材料以及物理衰老测量的生物测量。这项研究是罕见的 有机会阐明早期生活压力暴露与估计中年痴呆症风险的联系，确定 针对有针对性的AD/ADRD预防的脆弱亚组，阐明了社会询问在 确定AD痴呆症中的种族分布，并建立中年认知基线以供将来的随访 在这些异常良好的纵向，主要AA队列中。