White matter microstructure and executive functions in congenital heart disease from childhood to adulthood: A pooled case–control study

ABSTRACT

Congenital heart disease (CHD) patients are at risk for alterations in the cerebral white matter microstructure (WMM) throughout development. It is unclear whether the extent of WMM alterations changes with age, especially during adolescence when the WMM undergoes rapid maturation. We investigated differences in WMM between patients with CHD and healthy controls from childhood until early adulthood in a pooled sample of children, adolescents, and young adults. The association between WMM and EF was assessed. Patients with CHD (N=78) and controls (N=137) between 9 and 32 years of age underwent diffusion tensor imaging and an executive function test-battery. Mean fractional anisotropy (FA) was calculated for each white matter tract. Linear regression tested age and group effects (CHD vs control) and their interaction on FA. Relative Variable Importance (RI) estimated the independent contribution of tract FA, presence of CHD, CHD complexity, and parental education to the variability in EF. Mean FA was lower in patients compared to controls in almost all tracts (p between 0.057 and <0.001). WMM alterations in patients were not different depending on age (all interaction effects p>0.074). Predictors of EF were CHD group (RI=43%), parental education (RI=23%), CHD complexity (RI=10%), FA of the hippocampal cingulum (RI=6%) and FA of the corticospinal tract (RI=6%). The lack of group-FA-interactions indicates that the extent of altered FA remains similar across age. Altered FA is associated with EF impairments. CHD is a chronic disease with cerebral and neurocognitive impairments persisting into adulthood and, thus, long-term follow-up programs may improve overall outcome for this population.

KEYWORDS:

• Congenital heart disease
• executive functions
• neurodevelopment
• white matter microstructure
• diffusion tensor imaging

Acknowledgment

We thank all participants and their families, Lasse Bartels for his assistance with Relative Variable Importance, and Thorsten Weirauch and the whole team of MRI technicians for their valuable support in acquiring the MRI scans.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed at https://doi.org/10.1080/09297049.2022.2144633.

Additional information

Funding

This work was supported by the Swiss Heart Foundation, the Mäxi Foundation, the Olga-Mayenfisch Foundation, and the Swiss National Science Foundation (Project Number: 32003B_172914). The sponsors had no influence on study design, the collection, analysis, and interpretation of data, manuscript writing, or the decision to submit the paper for publication.