White matter microstructure and executive functions in congenital heart disease from childhood to adulthood: A pooled
Melanie Ehrler1,2,3, Peter Brugger4,5, Matthias Greutmann6
1Child Development Center, University Children's Hospital Zurich, Zurich, Switzerland.
Insights
Congenital heart disease (CHD) patients show altered white matter microstructure (WMM) across all ages. These WMM changes are linked to executive function (EF) impairments, persisting into adulthood.
Area of Science:
- Neuroscience
- Developmental Biology
- Cardiology
Background:
- Congenital heart disease (CHD) is linked to cerebral white matter microstructure (WMM) alterations.
- The developmental trajectory of WMM changes in CHD patients, particularly during adolescence, remains unclear.
- Understanding these alterations is crucial for long-term patient outcomes.
Purpose of the Study:
- To investigate age-related differences in WMM between CHD patients and healthy controls from childhood to early adulthood.
- To assess the association between WMM integrity and executive function (EF) in this population.
- To identify predictors of EF variability in CHD patients.
Main Methods:
- Diffusion tensor imaging (DTI) was used to assess WMM in 78 CHD patients and 137 controls (ages 9-32).
- Mean fractional anisotropy (FA) was calculated for white matter tracts.
- Linear regression and Relative Variable Importance (RI) analysis were employed to examine group, age, and predictor effects on WMM and EF.
Main Results:
- Mean FA was significantly lower in CHD patients compared to controls across most white matter tracts.
- WMM alterations in CHD patients did not differ significantly with age, indicating a consistent effect across development.
- Key predictors of EF included the presence of CHD (RI=43%), parental education (RI=23%), CHD complexity (RI=10%), and FA in specific tracts (hippocampal cingulum and corticospinal tract, RI=6% each).
Conclusions:
- The extent of white matter microstructure alterations in CHD patients remains consistent across development and is associated with executive function impairments.
- These neurocognitive deficits persist into adulthood, highlighting the need for long-term follow-up programs for CHD patients.
- Early and ongoing neurodevelopmental monitoring is essential for improving the overall health outcomes of individuals with CHD.
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.
