Continuation of the NuMoM2b Heart Health Study

项目摘要/摘要 妊娠相关因素可能在血管发育中发挥重要而未被认识的作用 对女性认知障碍和痴呆(VCID)的贡献。VCID现在被认为是一个密钥 阿尔茨海默病和相关痴呆的致病因素(ADRD)，是治疗阿尔茨海默病和相关痴呆的一个有希望的靶点 干预。先兆子痫和其他不良妊娠结局(APO)，如妊娠高血压， 早产和胎儿生长受限影响多达五分之一的孕妇，并与未来相关 产妇心脑血管风险。然而，载脂蛋白对母体VCID的影响仍然存在 未经审查。大多数现有的老年女性队列缺乏严格的表型，缺乏前瞻性的收集 妊娠数据，以及可能易患APOS和VCID的母亲因素的影响不是很好 明白了。2010-2013年间，未分娩妊娠结局研究：监测准妈妈 (NuMoM2B)在8个美国学术医疗中心招募了10,038名健康女性的不同队列，他们 从受孕初期到第一个孩子的出生都是如此。几年后， NuMoM2B心脏健康研究(nuMoM2B-HHS)将4508名nuMoM2B参与者带回进行第二项研究 波，以表征随后的妊娠结局和心血管危险因素的累积 在怀孕之后。第三次面对面访问的学习浪潮将于2022年初开始。使用此管理程序 作为补充，我们建议进行神经认知评估和脑磁共振 20例先兆子痫患者和20例正常对照的磁共振成像研究 APOS作为对照，在两个nuMoM2B-HHS临床点。本附录的目的是调查其影响 在这一独特的产科队列中，通过以下具体目标，研究先兆子痫对母亲VCID的影响：(1) 确定nuMoM2B-HHS中经历过先兆子痫的妇女是否有 与没有APOS的妇女相比，分娩后8-11年脑部MRI上VCID的早期标志物增加 对于指数或后续怀孕；以及(2)使用NIH工具箱认知电池评估 NuMoM2B-HHS患者的神经认知功能及其与脑MRI表现的相关性 经历过先兆子痫的孕妇和没有APOS的妇女。我们假设女性 先兆子痫患者在妊娠指标中会有较高的白质高信号体积和较低的白质高信号体积 与没有APO的女性相比，全球认知得分。通过利用这一异常良好的机会- 中年女性的表型队列，这种补充剂将使nuMoM2B-HHS调查人员获得罕见的 有机会使用前瞻性收集的怀孕数据来调查先兆子痫的影响，性行为- 特定的血管危险因素，对VCID和ADRD风险的影响。了解先兆子痫对早期妊娠的影响 VCID的标志物可以帮助我们在生命早期识别出患有ADRD风险较高的女性并发展为 预防策略，以阻止这一群体中认知能力下降的进展。

PROJECT SUMMARY/ABSTRACT Pregnancy-related factors may play an important and underrecognized role in the development of vascular contributions to cognitive impairment and dementia (VCID) in women. VCID is now recognized as a key pathogenic factor in Alzheimer's disease and related dementias (ADRD) and represents a promising target for intervention. Preeclampsia and other adverse pregnancy outcomes (APOs) such as gestational hypertension, preterm delivery, and fetal growth restriction affect up to one in five pregnancies and are associated with future maternal cardiovascular and cerebrovascular risk. However, the impact of APOs on maternal VCID remains unexamined. Most existing women's 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) enrolled a diverse cohort of 10,038 healthy women at eight U.S. academic medical centers, who were followed from early in conception through the delivery of their first child. Several years later, the nuMoM2b Heart Health Study (nuMoM2b-HHS) brought back 4,508 nuMoM2b participants 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. With this administrative supplement, we propose to conduct neurocognitive assessments and perform brain magnetic resonance imaging (MRI) on 20 women who had preeclampsia in the index pregnancy, along with 20 women with no APOs as controls, at two nuMoM2b-HHS clinical sites. The goal of this supplement is to investigate the impact of preeclampsia on maternal VCID in this unique obstetric cohort, through the following specific aims: (1) Determine if women in the nuMoM2b-HHS who experienced preeclampsia in the index pregnancy have increased early markers of VCID on brain MRI 8-11 years after delivery, compared with women with no APOs for either the index or subsequent pregnancies; and (2) Use the NIH Toolbox Cognition Battery to evaluate neurocognitive function, and correlate cognition with brain MRI findings, in women in the nuMoM2b-HHS who experienced preeclampsia in their index pregnancies and women without APOs. We hypothesize that women who had preeclampsia in the index pregnancy will have higher white matter hyperintensity volume and lower global cognition scores compared to women with no APOs. By capitalizing on this exceptionally well- phenotyped cohort of middle-aged women, this supplement will allow the nuMoM2b-HHS investigators a rare opportunity to use prospectively collected pregnancy data to investigate the impact of preeclampsia, a sex- specific vascular risk factor, on VCID and ADRD risk. Understanding the effects of preeclampsia on early markers of VCID could help us identify women early in life who are at higher risk of ADRD and develop preventive strategies to thwart the progression of cognitive decline in this population.