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: 10559052
• 负责人: Eliza C Miller
• 金额: $ 6.43万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-02 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10559052
• 关键词: Academic Medical Centers; Adverse event; Age; Aging; Ancillary Study; Back; Biological Markers; Brain imaging; Cardiac health; Cardiovascular system; Cerebral small vessel disease; Characteristics; Child; Cognition; Collection; Conceptions; Data; Dementia; Development; Discipline of obstetrics; Enrollment; Fetal Growth Retardation; Future; Goals; Hypertension; Impaired cognition; Intervention; Investments; Life; Mediating; Medical center; Monitor; Mothers; Neurocognitive; Nulliparity; Outcome Study; Participant; Persons; Phenotype; Placenta Diseases; Population; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Premature Birth; Prevention strategy; Prospective cohort; Risk; Site; Universities; Vascular Cognitive Impairment; Virulence Factors; Visit; White Matter Hyperintensity; Woman; adverse pregnancy outcome; brain magnetic resonance imaging; cardiovascular risk factor; cerebrovascular; cohort; dementia risk; high risk; indexing; magnetic resonance imaging biomarker; predictive modeling; prospective; sex; vascular cognitive impairment and dementia; vascular risk factor

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.

项目概要/摘要 血管对认知障碍和痴呆 (VCID) 的影响现已被认为是一个关键致病因素 痴呆症的一个因素，并代表了一个有希望的干预目标。不良妊娠结局（APO）， 如先兆子痫、早产和胎儿生长受限，这些都与未来的母亲有关。 心脑血管风险。然而，APO 对母亲 VCID 的影响仍然存在 未经审查。大多数现有女性心血管和衰老队列缺乏严格的表型， 前瞻性收集的妊娠数据，以及可能诱发两种 APO 的母体因素的影响 而VCID不太好理解。 2010-2013年未产妇妊娠结局研究监测 准妈妈 (nuMoM2b) 研究在 8 个美国学术医学中心招募了 10,037 名健康女性的不同队列 中心对她们从受孕早期到第一个孩子的分娩进行跟踪。几年后， 未产妊娠结局研究：监测准妈妈心脏健康研究 (nuMoM2b-HHS) 带回 4,475 名 nuMoM2b 女性进行第二轮研究，以描述随后怀孕的特征 妊娠后心血管危险因素的结果和积累。第三波面对面研究 访问将于 2022 年初开始。在这项辅助研究中，我们建议对所有 第三轮研究期间的 nuMoM2b-HHS 参与者。我们将进行脑部磁共振成像 (MRI) 对哥伦比亚大学欧文医学中心研究中心的 250 名女性小组进行了跟踪研究， 包括所有在初次妊娠期间经历过 APO 的人。该研究的总体目标是利用 这个独特的产科队列旨在确定 APO 对长期母亲 VCID 的影响，通过 具体目标如下： (1) 研究 APO 对产后 10-15 年产妇认知的影响 比较经历过 APO 的女性和没有经历过 APO 的女性的整体认知得分； (2) 确定 APO 对母体 VCID 的 MRI 生物标志物（包括白质高信号）的影响 体积和脑小血管疾病的其他标志物。我们假设 APO 的关联 VCID 标记物的发生将部分由妊娠后新发高血压的发生介导。 作为探索性目标，我们将使用深度妊娠表型分析，包括母体特征、生物标志物 缺血性胎盘疾病和 APO，创建 VCID 预测模型。这将是美国第一项研究 使用前瞻性收集的妊娠数据来研究 APO（一种性别特异性血管风险）的影响 影响女性 VCID 的因素。了解 APO 对 VCID 早期标志物的影响可以帮助我们识别 年轻时患痴呆症的风险较高，并制定预防策略来阻止这种情况的发生 该人群认知能力下降的进展。此外，收集神经认知评估 本次研究浪潮中的整个 nuMoM2b-HHS 队列是一项重要投资，它将提供基线 随着这些女性继续老龄化，为未来的研究提供数据。