Brain health in individuals with congenital heart disease: similarities and differences related to sex - an overview across the lifespan

As survival in congenital heart disease (CHD) continues to improve, there is an increasing focus and growing body of literature on the implications for neurological and mental health across the life course in individuals with CHD. One important aspect that remains underexplored, however, is how sex may impact the relationship between brain health and CHD. In this narrative review, we present the known sex-related differences with respect to neurodevelopment, cognition, stroke risk, dementia, and mental health in individuals with CHD from birth through old age. Notably, boys with CHD appear more vulnerable to early neurodevelopmental delays and neurological injury, while girls with CHD show a distinct pattern of mental health challenges, including higher rates of anxiety and depression. Risks for stroke become more pronounced with age in this population, particularly in women with CHD who become pregnant. Brain health in the elderly with CHD remains an emerging area of research, and recent studies suggest earlier dementia onset in men with CHD. Overall, there is a growing need for sex-specific healthcare strategies to optimize outcomes for this growing, vulnerable population. Personalized approaches to clinical care, preventative strategies, and treatment across the life course will be facilitated through longitudinal research in CHD that both incorporate dedicated sex-related analyses and advances mechanistic understanding of the biological and psychosocial pathways for neurodevelopment, brain injury, and neurodegeneration in CHD.