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

项目总结/摘要 血管对认知障碍和痴呆（VCID）的贡献现在被认为是一个关键的致病因素， 痴呆症的因素，并代表了一个有希望的干预目标。不良妊娠结局（APO）， 例如先兆子痫、早产和胎儿生长受限，与未来母亲 心血管和脑血管风险。然而，APO对母体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队列缺乏严格的表型， 前瞻性收集妊娠数据，以及可能导致两种APO的母体因素的影响 并且VCID没有被很好地理解。2010-2013年未产妊娠结局研究监测 准妈妈（nuMoM 2b）研究在美国8个学术医学中心招募了10，037名健康女性的多样化队列 这些研究人员从怀孕早期到第一个孩子的出生都进行了跟踪。几年后， 未产妊娠结局研究：监测准妈妈心脏健康研究（nuMoM 2b-HHS） 在第二次研究中，4,475名nuMoM 2b妇女被带回，以描述随后怀孕的特征。 妊娠后心血管危险因素的累积和结局。第三波面对面学习 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。 nuMoM 2b-HHS参与者在这第三个研究波。我们将进行脑部磁共振成像 (MRI)在哥伦比亚大学欧文医学中心的研究地点， 包括所有在首次妊娠中发生APO的患者。这项研究的总体目标是利用 这一独特的产科队列，以确定APO对长期孕产妇VCID的影响，通过 以下具体目标：（1）调查APO对分娩后10-15年母亲认知的影响， 比较经历过APO的女性和没有经历过APO的女性之间的整体认知得分;（2） 确定APO对母体VCID MRI生物标志物的影响，包括白色高信号 脑小血管疾病的体积和其他标志物。我们假设载脂蛋白结合 与VCID标志物的结合将部分由指数妊娠后新的高血压的发展介导。 作为一个探索性的目标，我们将使用深妊娠表型，包括母体特征，生物标志物 缺血性胎盘疾病和APO的关系，以建立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研究APO的影响，APO是一种性别特异性血管风险 因素，对女性的VCID。了解载脂蛋白对VCID早期标志物的影响可以帮助我们识别 老年痴呆症风险较高的妇女，并制定预防战略， 认知能力下降的进展。此外，收集神经认知评估， 在本研究波期间，整个nuMoM 2b-HHS队列是一项重要的投资，它将提供基线 随着这些女性年龄的增长，未来的研究数据。

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.