Abstract
Children and adolescents with congenital heart disease (CHD) are at risk for mild to moderate cognitive impairments. In particular, impaired working memory performance has been found in CHD patients of all ages. Working memory is an important domain of higher order cognitive function and is crucial for everyday activities, with emerging importance in adolescence. However, the underlying neural correlate of working memory impairments in CHD is not yet fully understood. Diffusion tensor imaging and tract based spatial statistics analyses were conducted in 47 adolescent survivors of childhood cardiopulmonary bypass surgery (24 females) and in 44 healthy controls (24 females) between 11 and 16 years of age (mean age=13.9, SD=1.6). Fractional anisotropy (FA) of white matter diffusion was compared between groups and was correlated with working memory performance, derived from the Wechsler Intelligence Scale for Children-IV. CHD patients had significantly poorer working memory compared to controls (p=0.001). Widespread bilateral reduction in FA was observed in CHD patients compared to healthy controls (threshold-free cluster enhancement (TFCE) corrected p < 0.05). This reduction in FA was present both in cyanotic and acyanotic CHD patients compared to healthy controls (both p < 0.001). The FA reduction in the frontal lobe, mainly in the forceps minor, was associated with poorer working memory performance in both patients with CHD and healthy controls (TFCE corrected p < 0.05). The current findings underline that in CHD patients, irrespective of disease severity, disrupted or delayed maturation of white matter may persist into adolescence and is associated with working memory impairments, particularly if present in the frontal lobe. Adolescence, which is a crucial period for prefrontal brain maturation, may offer a window of opportunity for intervention in order to support the maturation of frontal brain regions and therefore improve higher order cognitive function in patients with CHD.
Highlights
It is well recognized that patients with severe congenital heart disease (CHD) undergoing open-heart surgery are at risk for mild to moderate cognitive impairments (Latal, 2016)
The current study provides strong evidence that altered white matter microstructure measured as reduced fractional anisotropy (FA) in the bilateral frontal cortex is associated with impaired working memory
In adolescents with various types of CHD, who underwent cardiopulmonary bypass surgery during infancy and early childhood, widespread bilateral changes in white matter microstructure were observed compared to healthy controls
Summary
It is well recognized that patients with severe congenital heart disease (CHD) undergoing open-heart surgery are at risk for mild to moderate cognitive impairments (Latal, 2016). Previous studies have shown that working memory impairments occur more frequently in CHD patients than in the typically developing population during childhood (Calderon et al, 2010) and adolescence (Bellinger et al, 2015b; Schaefer et al, 2013), and may persist into adulthood (Ilardi et al, 2017; Murphy et al, 2015). These impairments manifest themselves in both the school and home settings and are of particular relevance (Cassidy et al, 2014; Sanz et al, 2017). In preterm-born adolescents, a population with a similar profile of cognitive deficits as in CHD patients (Easson et al, 2018), reduced anisotropy of white matter microstructure was observed compared to term-born children and was associated with working memory impairments (Vollmer et al, 2017)
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