Altered white matter microstructure is related to cognition in adults with congenital heart disease

Abstract

Adults with congenital heart disease are at risk for persisting executive function deficits, which are known to affect academic achievement and quality of life. Alterations in white -matter microstructure are associated with cognitive impairments in adolescents with congenital heart disease. This study aimed to identify microstructural alterations potentially associated with executive function deficits in adults with congenital heart disease. Diffusion tensor imaging and tract-based spatial statistics were conducted in 45 patients (18 females) and 54 healthy controls (26 females) aged 18–32 years. Fractional anisotropy of white matter diffusion was compared between groups and correlated with an executive function score, derived from an extensive neuropsychological test battery. Patients showed widespread bilateral reduction in fractional anisotropy (P < 0.05, multiple comparison corrected) compared to controls. Lower fractional anisotropy was driven by patients with moderate and severe defect complexity (compared to controls: P < 0.001). Executive function scores were lower in patients (P < 0.05) and associated with lower fractional anisotropy in the left superior corona radiata and the corticospinal tract (corrected P < 0.05). Our findings confirm alterations of white matter microstructure in adults with congenital heart disease, mainly in those patients of moderate to severe complexity. These alterations are associated with impairments in executive functioning. A better understanding of the neurocognitive deficits may help counselling and care of patients with congenital heart disease across their lifespan and have the potential to improve their outcome and quality of life.

Microstructural alterations of the corticospinal tract are associated with poor motor function in patients with severe congenital heart disease

“…Thus, lower FA in CHD patients may provide evidence for alterations in the white matter microstructure but not for specific properties underlying these alterations. Previous studies have demonstrated that altered white matter microstructure in CHD is not restricted to the CST but is a rather global trait evident across the whole brain ( Brewster et al, 2015 , Ehrler et al, 2021 , Ehrler et al, 2020 , Rollins et al, 2014 , Watson et al, 2018 ), which can already be detected postnatally and is associated with decreased oxygen delivery ( Karmacharya et al, 2018 , Kelly et al, 2019 ). Of note is that two previously conducted studies in adolescents with CHD did not find any significant difference in FA of the CST compared to controls, while there was significantly lower FA in other major tracts ( Easson et al, 2020 , Watson et al, 2018 ).…”

“…Sample 2 includes adult patients with different types of CHD, who were treated at the outpatient clinic of the University Hospital Zurich, Switzerland (for details see ( Ehrler et al, 2021 )). Sixty-six patients agreed to participate in the study, of whom 46 patients underwent an MRI scan.…”

“…The distribution of residuals was examined to evaluate normality. FA was considered as the primary DTI measure of interest as previous DTI studies have used this measure to investigate microstructural alterations in CHD patients and their neurodevelopmental correlates ( Brewster et al, 2015 , Ehrler et al, 2021 , Ehrler et al, 2020 , Rollins et al, 2014 , Watson et al, 2018 ). However, post hoc, the above-described analyses were performed for secondary DTI measures, namely MD and RD.…”

“…A study in CHD neonates, who underwent brain MRI with diffusion tensor imaging (DTI) and continuous EEG-monitoring, showed that patients with delayed microstructural development had significantly stronger high-frequency connectivity and significantly weaker low-frequency connectivity, suggesting that delayed microstructural brain development has immediate functional consequences in CHD patients ( Birca et al, 2016 ). Studies in adolescents and young adults with CHD revealed that altered white matter microstructure, measured by means of lower fractional anisotropy (FA), was associated with a range of cognitive impairments ( Brewster et al, 2015 , Ehrler et al, 2021 , Ehrler et al, 2020 , Rollins et al, 2014 , Watson et al, 2018 ). However, while these neuroimaging studies have helped to elucidate the relationship between brain microstructural alterations and cognitive function in the CHD population, relatively little is known about the neuroanatomical correlates of persistent motor deficits, and there is a need for further investigation to better predict neurodevelopmental outcomes in CHD patients ( Peyvandi et al, 2019 ).…”

Neurodevelopmental and Mental Health Outcomes in Patients With Fontan Circulation: A State-of-the-Art Review

“…As the population with Fontan circulation ages, further research is needed to assess the translation of neurodevelopmental and behavioral findings in childhood and adolescence into neurocognitive function in adulthood. Recent studies show that adults with CHD are at risk for persisting neurocognitive deficits, particularly in the domain of executive functions ( 69 ), which may alter their professional and personal achievement and quality of life. These deficits seem correlated to alterations of white matter microstructure in subjects with severe CHD, suggesting long-lasting neurological effects of critical CHD for some adults.…”