Vascular Contributions to Cognitive Impairment after Adverse Pregnancy Outcomes: the nuMoM2b-Heart Health Study

血管对不良妊娠结果后认知障碍的影响：nuMoM2b-心脏健康研究

• 批准号: 10275504
• 负责人: Eliza C Miller
• 金额: $ 82.73万
• 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: 2021-07-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10275504
• 关键词: Academic Medical Centers; Adverse event; Affect; Age; Aging; Ancillary Study; Arteries; Back; Biological Markers; Brain; Brain imaging; Cardiac health; Cardiovascular system; Cerebral small vessel disease; Cerebrovascular Circulation; Cerebrovascular Disorders; Characteristics; Child; Clinical; Cognition; Collection; Conceptions; Data; Dementia; Development; Diagnosis; Discipline of obstetrics; Enrollment; Ethnic Origin; Fetal Growth Retardation; Funding; Future; Goals; Hypertension; Impaired cognition; Intervention; Investments; Lacunar Infarctions; Life; Longitudinal cohort study; Machine Learning; Magnetic Resonance Imaging; Maternal-fetal medicine; Measures; Mediating; Medical center; Monitor; Mothers; National Heart, Lung, and Blood Institute; National Institute of Child Health and Human Development; Neurocognitive; Nulliparity; Outcome Study; Participant; Persons; Phenotype; Placenta Diseases; Population; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Prevention strategy; Prospective cohort; Race; Risk; Risk Factors; Serum; Sex Differences; Site; Socioeconomic Status; Techniques; Time; United States National Institutes of Health; Universities; Uterus; Vascular Cognitive Impairment; Virulence Factors; Visit; Weight Gain; White Matter Hyperintensity; Woman; adjudicate; adverse pregnancy outcome; cardiovascular risk factor; cerebrovascular; cognitive performance; cohort; dementia risk; effective therapy; high risk; imaging biomarker; indexing; magnetic resonance imaging biomarker; predictive marker; predictive modeling; primary outcome; prospective; sex; vascular cognitive impairment and dementia; vascular risk factor; white matter

PROJECT SUMMARY/ABSTRACT Vascular contributions to cognitive impairment and dementia (VCID) are now recognized as a key pathogenic factor in dementia, and represent a promising target for intervention. Adverse pregnancy outcomes (APOs), such as preeclampsia, preterm delivery, and fetal growth restriction, are associated with future maternal cardiovascular and cerebrovascular risk. However, the impact of APOs on maternal VCID remains unexamined. Most existing women's cardiovascular and aging cohorts lack rigorously phenotyped, prospectively collected pregnancy data, and the impact of maternal factors that may predispose to both APOs and VCID is not well understood. From 2010-2013, the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be (nuMoM2b) study enrolled a diverse cohort of 10,037 healthy women at 8 US academic medical centers, who were followed from early in conception through the delivery of their first child. Several years later, the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be Heart Health Study (nuMoM2b-HHS) brought back 4,475 nuMoM2b women for a second study wave, to characterize subsequent pregnancy outcomes and accumulation of cardiovascular risk factors following pregnancy. A third study wave of in-person visits will begin in early 2022. In this ancillary study, we propose to conduct neurocognitive assessments on all nuMoM2b-HHS participants during this third study wave. We will perform brain magnetic resonance imaging (MRI) on a sub-cohort of 250 women followed at the Columbia University Irving Medical Center study site, including all who experienced APOs in the index pregnancy. The overall goal of the study is to capitalize on this unique obstetric cohort to determine the impact of APOs on long term maternal VCID, through the following specific aims: (1) Investigate the impact of APOs on maternal cognition 10-15 years after delivery by comparing global cognition scores between women who experienced APOs and women who did not; (2) Determine the impact of APOs on MRI biomarkers of maternal VCID, including white matter hyperintensity volume and additional markers of cerebral small vessel disease. We hypothesize that the association of APOs with VCID markers will be partially mediated by development of new hypertension after the index pregnancy. As an exploratory aim, we will use deep pregnancy phenotyping, including maternal characteristics, biomarkers of ischemic placental disease and APOs, to create a VCID prediction model. This will be the first US study to use prospectively collected pregnancy data to investigate the impact of APOs, a sex-specific vascular risk factor, on VCID in women. Understanding the effects of APOs on early markers of VCID could help us identify women early in life who are at higher risk of dementia, and develop preventive strategies to thwart the progression of cognitive decline in this population. In addition, the collection of neurocognitive assessments on the entire nuMoM2b-HHS cohort during this study wave is an important investment, which will provide baseline data for future studies as these women continue to age.

项目摘要/摘要 对认知障碍和痴呆（VCID）的血管贡献现在被认为是关键的致病性 痴呆症的因素，代表了有希望的干预目标。不良怀孕结果（APO）， 例如先兆子痫，早产和胎儿生长限制与未来的母亲有关 心血管和脑血管风险。但是，Apos对母亲VCID的影响仍然存在 未经检查。大多数现有的女性心血管和衰老人群都缺乏严格的表型， 前瞻性收集的妊娠数据，以及可能易于apos的产妇因素的影响 VCID并没有很好地理解。从2010年至2013年，无效的妊娠结局研究监测 准母亲（NUMOM2B）研究在美国8个学术医学中招募了10,037名健康女性的各种各样的队列 中心，从构思早期开始，通过分娩第一个孩子。几年后， 无效的怀孕结果研究：监测准母亲的心脏健康研究（NUMOM2B-HHS） 带回了4,475名Numom2b女性进行第二次研究浪潮，以表征随后的怀孕 怀孕后心血管危险因素的结果和积累。第三个研究浪潮 访问将于2022年初开始。在这项辅助研究中，我们建议对所有人进行神经认知评估 在第三个研究浪潮中的Numom2B-HHS参与者。我们将执行大脑磁共振成像 （MRI）在哥伦比亚大学欧文医学中心研究地点的250名妇女的亚军上， 包括所有在指数怀孕中经历过APO的人。该研究的总体目标是利用 这种独特的产科同伴通过 以下具体目的：（1）研究Apos在分娩后10 - 15年对孕产妇认知的影响 比较经历APO的女性与没有的女性之间的全球认知评分； （2） 确定APO对母体VCID的MRI生物标志物的影响，包括白质超强度 脑小血管疾病的体积和其他标记。我们假设Apos的关联 用VCID标记将部分通过指数妊娠后新高血压的发展进行部分介导。 作为探索目的，我们将使用深层怀孕表型，包括母体特征，生物标志物 缺血性胎盘疾病和APO，以创建VCID预测模型。这将是美国第一次学习 使用前瞻性收集的妊娠数据来研究APO的影响，APO是一种性别特异性的血管风险 因素，关于女性的VCID。了解APO对VCID早期标记的影响可以帮助我们识别 妇女在生活的早期痴呆症风险较高，并制定预防策略来阻止 该人群认知能力下降的进展。此外，收集了有关神经认知评估 在本研究浪潮期间的整个Numom2B-HHS队列是一项重要的投资，它将提供基线 随着这些妇女的年龄，未来研究的数据。