R01NS122815

Vascular Contributions to Cognitive Impairment After Adverse Pregnancy Outcomes: The NUMOM2B-Heart Health Study - 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 the 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.

The Trustees Of Columbia University In The City Of New York

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM, RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS, RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS, IMPROVED METHODS OF DISEASE PREVENTION, NEW METHODS OF DIAGNOSIS AND TREATMENT, DRUG DEVELOPMENT, DEVELOPMENT OF NEURAL DEVICES, CLINICAL TRIALS, AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH, SYNAPSE FORMATION, FUNCTION, AND PLASTICITY, LEARNING AND MEMORY, CHANNELS, TRANSPORTERS, AND PUMPS, CIRCUIT FORMATION AND MODULATION, BEHAVIORAL AND COGNITIVE NEUROSCIENCE, SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION, NEUROENDOCRINE SYSTEMS, SLEEP AND CIRCADIAN RHYTHMS, AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE, TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM, NEURODEGENERATIVE DISORDERS, MOVEMENT DISORDERS, BRAIN TUMORS, CONVULSIVE DISORDERS, INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS, DISORDERS RELATED TO SLEEP, AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE NEUROSCIENCE WORKFORCE DEVELOPMENT, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM, TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

National Institute on Aging (NIA) [HHS - NIH]

New York United States

State-Wide

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the End Date has been shortened from 06/30/26 to 02/28/25 and the total obligations have increased 1879% from $142,066 to $2,811,295.