Congenital heart disease is associated with reduced cortical and hippocampal volume in patients with 22q11.2 deletion syndrome

Abstract

Objective: There is increasing evidence that congenital heart disease (CHD) affects brain structure, but little is known about the long-term trajectory of brain maturation and its impact on the cognitive development of patients with CHD. We proposed to address this question in a longitudinally-followed cohort of individuals with 22q11.2 deletion syndrome (22q11DS), the most common microdeletion syndrome in humans.

Methods: A total of 80 participants were included in this longitudinal analysis. The volumes of thirty-four cortical regions and eight hippocampal regions were measured in each hemisphere with FreeSurfer software. This paper utilized linear mixed modelling to investigate cerebral morphometry and age-related maturational changes of all regions. The effect of CHD was assessed for intercept and slope significance.

Results: We observed significant (p < .05/34) volumetric reductions in patients with CHD compared to patients without in fifteen out of the sixty-eight cortical sub-regions. Similarly, global hippocampal volumes and twelve of the hippocampal sub-regions were significantly smaller (p < .05/8). The results demonstrate significant absolute volumetric differences, but did not show any significant differences in the way the cortical or hippocampal regions developed over time. There was limited evidence of any effect of the presence of CHD on key cognitive measures.

Conclusions: We propose that cerebral hypoperfusion, due to the presence of CHD or its surgery, impairs early cortical and particularly hippocampal growth, potentially due to the damaging effects of stress, but not subsequent maturational processes in children and adolescents.

Keywords: Brain morphometry; Cardiac defects; Neurodevelopmental disorders; Velo-cardio-facial syndrome; Volumetric MRI.