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 ...