Building an unbiased pooled cohort for the study of lifecourse social and vascular determinants of Alzheimer's Disease and Related Disorders

建立一个无偏见的队列研究阿尔茨海默病和相关疾病的生命周期社会和血管决定因素

• 批准号: 10426258
• 负责人: Medellena Maria Glymour
• 金额: $ 78.56万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-15 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10426258
• 关键词: Address; Adolescent; Adopted; Adult; Affect; African American population; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Attenuated; Birth; Black American; Black Populations; Black race; Blood Vessels; Body Weight decreased; Child; Childhood; Cohort Studies; Coronary artery; Data; Data Collection; Data Set; Data Sources; Dementia; Development; Diagnosis; Disease; Elderly; Enrollment; Etiology; Evaluation; Face; Genetic Risk; Goals; Health; Health and Retirement Study; Heart; Impaired cognition; Individual; Intervention; Lead; Life; Longitudinal Studies; Mendelian randomization; Methodology; Methods; Modeling; National Health and Nutrition Examination Survey; National Longitudinal Survey of Youth; Obesity; Pattern; Phase; Positioning Attribute; Prevention; Process; Public Health; Research; Risk; Risk Factors; Role; Sampling; Socioeconomic Factors; Stroke; Structure; Time; Walking; Woman; base; biological sex; caucasian American; cohort; cost; dementia risk; emerging adult; geographic disparity; high risk; improved; men; middle age; multiple data sources; nutrition; prevent; protective factors; racial disparity; research study; social; social factors; socioeconomic disadvantage; tool; vascular factor; vascular risk factor; young adult

Abstract Critical social and vascular risk factors for Alzheimer’s disease and related dementias (ADRD) occur in childhood, early adulthood, or midlife, decades before ADRD is typically diagnosed. Most cohorts dedicated to the study of aging are initiated in mid to late life, and are therefore not ideal for evaluating the effects of early life risk factors. Synthetic cohorts, which pool multiple data sources that in combination span early to late life, provide an unparalleled opportunity to rigorously evaluate lifecourse mechanisms of ADRD. Lifecourse research, especially when based on synthetic cohorts, faces several methodological challenges related to survival, enrollment and attrition that are differential across the pooled studies, and reverse causation from incipient dementia. The long-term goal of our research is to pinpoint how and when we can intervene to prevent or delay the onset of ADRD. Yet, the differential selection forces in a synthetic cohort can make it impossible to identify protective factors, can spuriously make harmful factors appear innocuous, and can provide incorrect guidance on prevention priorities. In this study, we propose to pool eight data sources comprising children, young, middle-aged, and older adults to create a SYNthetic Birth cohort for research on ADRD (SynBAD), correcting for differential survival, enrollment or attrition, and reverse causation, allowing us to rigorously evaluate the effects of lifecourse social and vascular risk factors. SynBAD will include the Bogalusa Heart Study, the Muscatine study, the National Longitudinal Survey of Youth 1979, The National Longitudinal Study of Adolescent to Adult Health, the Coronary Artery Risk in Development in Young Adults, the Health and Retirement Study, the REasons for Geographic And Racial Disparities in Stroke, and the National Health and Nutrition Examination Studies. SynBAD will be large (N=304,171) and exceptionally diverse, facilitating research on the drivers of ADRD among women (56%) and Black individuals (25%). Specifically, we propose to (Aim 1) create a diverse synthetic birth cohort (age 0 to 90) for the study of social and vascular risk factors for ADRD, incorporating corrections for differential survival, enrollment, and attrition; (Aim 2), evaluate and correct for reverse causation -- in which incipient dementia induces changes in risk factors -- by using a reverse Mendelian Randomization approach based on identifying the age-specific effects of a genetic risk score for ADRD on risk factors; (Aim 3), rigorously estimate the causal effects of social and vascular factors on ADRD risk using the synthetic cohort corrected for selection and reverse causation biases; and (Aim 4), quantify reduction in lifetime ADRD cases and ADRD racial disparities that could be achieved with a variety of hypothetical interventions on social or vascular risk factors at different ages. Given the role of biological sex with social and vascular risk factors and dementia risk, we will allow for distinct risk models for men and women. This study will improve the validity of lifecourse research using synthetic cohorts and provide more valid and public health relevant estimates of the effects of social and vascular determinants of ADRD.

抽象的 阿尔茨海默氏病和相关痴呆症（ADRD）的关键社会和血管危险因素发生在 通常诊断出ADRD之前的几十年，童年，成年或中年。大多数人群致力于 对衰老的研究是在中期至后期开始的，因此并不理想评估早期的影响 生活风险因素。合成队列，汇总组合早期至后期的多个数据源， 提供无与伦比的机会来严格评估ADRD的生命力机制。生命 研究，尤其是基于合成队列的研究，面临着与 在合并研究中有差异的生存，入学和属性，并从 初期痴呆。我们研究的长期目标是指出如何以及何时干预 预防或延迟ADRD的发作。然而，合成队列中的差分选择力可以使它成为 无法识别受保护的因素，可能使有害因素显得无害，并且可以 提供有关预防优先级的不正确指导。在这项研究中，我们建议汇总八个数据源 建立儿童，年轻，中年和老年人，以创建一个合成的出生队列 ADRD（Synbad），纠正差异生存，入学或流失和反向原因，使我们允许我们 严格评估生命性的社会和血管危险因素的影响。 Synbad将包括 Bogalusa心脏研究，马斯喀汀研究，《国家青年纵向调查》，1979年，国家 青少年对成人健康的纵向研究，年轻人的发展风险， 健康和退休研究，中风中的地理和种族差异的原因以及 国家健康和营养考试研究。 Synbad将很大（n = 304,171），并且异常 潜水员，支持女性（56％）和黑人（25％）的ADRD驱动因素的研究。 特别是，我们建议（AIM 1）创建潜水员合成出生队列（0至90岁）进行社会研究 以及ADRD的血管危险因素，并结合差异生存，入学和损耗的校正； （AIM 2），评估并正确以逆转原因 - 初期痴呆会影响风险变化 因素 - 通过使用反向孟德尔随机方法来识别特定年龄的效果 风险因素的ADRD遗传风险评分； （AIM 3），严格估计社会的因果影响 使用合成队列进行校正以选择和反向病毒偏见的合成队列的ADRD风险的血管因素； （AIM 4），量化终生案例的减少和ADRD种族分布可以实现 在不同年龄段的社会或血管危险因素上进行了多种假设干预措施。鉴于 具有社会和血管危险因素以及痴呆症风险的生物性行为，我们将为不同的风险模型 男女。这项研究将提高使用合成队列的生命力研究的有效性，并提供 对ADRD的社会和血管决定者的影响的更有效和公共卫生的相关估计。