Previously lethal, critical congenital heart disease (CHD) can now be treated effectively with surgical, catheter, and medical interventions. The resulting dramatic improvement in life expectancy has brought a major demographic shift, so that adult patients with CHD now outnumber children with CHD, even for complex conditions. Adult survivors are at increased risk of anxiety, depression, social difficulties, lower educational attainment, and underemployment. These psychosocial morbidities may be associated with deficits in executive functions (EFs) and other neurocognitive abilities that are prevalent in children and adolescents with CHD. Deficits in EFs, represented by measures of inhibitory control, working memory, cognitive flexibility, and decision-making, are highly dependent on the integrity of cortical and subcortical neural networks that continue to develop into early adulthood and can have a major adverse impact on self-regulation and management. The goal of our proposal is to bridge the gap in knowledge between known executive function deficits in childhood CHD and adult well-being. We propose to accomplish our goal by studying subjects, now age 24-28 years, who were enrolled as infants in the Boston Circulatory Arrest Study and then studied with respect to neurolopsychological and developmental function at ages 1, 2.5, 4, 8, and 16 years, as well as with brain MRI at 16 years.
In Aim 1, we will explore the relationship of EFs to major dimensions of adult well-being. We hypothesize that lower performance on EFs will be related to poorer overall well-being. The outcomes measured to determine well-being will be quality of life, neuropsychological function (e.g. social cognition, memory skills), mental health diagnosis and function (e.g. anxiety, depression), social relatedness, academic achievement, and adult independence (e.g. employment status, medical follow up).
In Aim 2, we will determine the relationship of EFs to MRI-derived measures of brain structure, function, and connectivity. We hypothesize that lower performance on EFs will be associated with lower global efficiency (integration) and higher modularity (segregation). We will measure the brain MRI outcomes using global white matter connectivity, regional cortical gray matter thickness, gray matter connectivity measured from interregional correlation in cortical thickness, and functional connectivity as defined by resting state functional magnetic resonance imaging.
In Aim 3, we will use longitudinal models to analyze the association of adult well-being with earlier measures of EFs and other neurocognitive and mental health variables, as well as with earlier clinical variables and adolescent neuroimaging. We will analyze associations of adult well-being dimensions with childhood and adolescent EFs, other measures of mental health and cognitive function, adolescent brain MRI findings, and clinical variables. Our ultimate goal is to identify early, modifiable risk factors for adult performance to guide the design of targeted treatment strategies that optimize educational achievement, employability, and quality of life in the burgeoning population of adults with CHD.

Public Health Relevance

In the landmark Boston Circulatory Arrest Study, neurologic and developmental status was measured following infant heart surgery and then prospectively at ages 1, 2.5, 4, 8, and 16 years, with findings of significant neurocognitive deficits and brain MRI abnormalities regardless of operative management. To date, no study has evaluated the neuropsychological and neuroimaging antecedents and correlates of well-being in adults with congenital heart disease, a population now >1 million and projected to grow at 5% per year. We propose to study the Boston cohort at ages 24-28 years to assess the associations of adult well-being with childhood and adolescent executive function, other measures of mental health and cognitive function, adolescent brain MRI findings, and clinical variables; findings will guide the design of interventions in childhood to optimize outcomes in adults with congenital heart disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL135061-02
Application #
9418107
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Burns, Kristin
Project Start
2017-02-01
Project End
2021-01-31
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Boston Children's Hospital
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115