Hippocampal volume and cognitive performance in children with congenital heart disease

Background: Congenital heart disease (CHD) is associated with an increased risk of brain abnormalities. Studies indicate a particular vulnerability of the hippocampus to hypoxia and inflammation. Yet, information regarding the hippocampus and its relation to cognitive function in school-age children with CHD remains scarce. Methods: Children who underwent cardiopulmonary bypass surgery for CHD (N = 17) and healthy controls (N = 14) at 10 years of age underwent neurodevelopmental assessment and cerebral magnetic resonance imaging to measure IQ, working memory performance and hippocampal volume. Results: IQ was significantly lower in children with CHD compared to controls (98 vs 112, P = 0.02). Children with CHD showed worse working memory performance with significantly lower scores in the letter-number sequencing test (P = 0.02). After adjusting for total brain volume, hippocampal volume was smaller in children with CHD compared to controls (P 0.1). Conclusion: This study suggests that the hippocampus may be particularly susceptible in children with CHD thereby contributing to cognitive impairments. Further research is necessary to understand the contribution of the hippocampus to cognitive impairments in children with CHD. Impact: IQ is significantly lower in school-age children with congenital heart disease compared to controls. Working memory performance seems to be worse in children with congenital heart disease. Smaller hippocampal volume is associated with lower IQ and seems to be associated with lower working memory performance. The study adds knowledge on the etiology of cognitive impairments in school-age children with congenital heart disease

Association of cerebellar volume with cognitive and motor function in adults with congenital heart disease

INTRODUCTION Patients with congenital heart disease (CHD) are at risk for cognitive and motor function impairments, brain injury, and smaller total brain volumes. The specific vulnerability of the cerebellum and its role in cognitive and motor functions in adults with congenital heart disease is not well defined. METHODS Forty-three patients with CHD and 53 controls between 18 and 32 years underwent brain magnetic resonance imaging and cognitive, executive (EF), and motor function assessment. Cerebellar volumes were obtained using EasyMeasure and SUIT Toolbox. Associations between cerebellar volumes and cognitive and motor function were calculated using linear models. RESULTS General cognitive and pure motor functions were lower in patients compared to controls (P 0.1), the posterior cerebellar lobe was smaller in patients with more complex CHD (P = 0.006). Smaller posterior cerebellar gray matter was not associated with cognitive functions. Smaller anterior cerebellar gray matter was not significantly related to motor functions (P > 0.1). CONCLUSION In adults with CHD, cerebellar volume was largely unimpaired. Patients with more complex CHD may be vulnerable to changes in the posterior cerebellar gray matter. We found no significant contribution of cerebellar gray matter to cognitive and motor impairments. More advanced imaging techniques are necessary to clarify the contribution of the cerebellum to cognitive and motor functions

Brain volumes in adults with congenital heart disease correlate with executive function abilities

Congenital heart disease is the most common birth defect, and patients are at risk for neurodevelopmental impairment and brain abnormalities. Yet, little is known about the link between brain volumes and cognitive function in adults with congenital heart disease. Forty-four patients and 53 controls between 18 and 32 years underwent brain magnetic resonance imaging and cognitive testing, assessed with an intelligence quotient and executive function global score. Associations between brain volumes and cognitive function were calculated using linear models. Cognitive function in patients was within the normal range (intelligence quotient: 97.74 (10.76)). Total brain volume was significantly smaller in patients compared to controls (1067.26 (113.53) vs 1113.04 (97.88) cm3, P 0.4). After adjusting for total brain volume, only corpus callosum volume remained significantly smaller (P = 0.03). Smaller total brain volume was associated with poorer overall executive functioning (P = 0.02) and inhibition (P < 0.01), in both patients and controls. The association between total brain volume and overall executive functioning was moderated by parental socioeconomic status (lower socioeconomic status was associated with a stronger association between brain volume and EF; interaction P = 0.03). In adults with congenital heart disease, despite normal intelligence quotient, brain volume alterations persist into adulthood and are related to executive functioning, in particular inhibitory control. Adults coming from low socioeconomic background and with altered brain volumes are especially vulnerable and should thus be followed-up during adulthood to ensure optimal social and educational support. Keywords: ACHD; Brain imaging; Brain volume; Congenital heart disease; Executive function

Stress Markers, Executive Functioning, and Resilience Among Early Adolescents With Complex Congenital Heart Disease

Importance: Infants with complex congenital heart disease (cCHD) may experience prolonged and severe stress when undergoing open heart surgery. However, little is known about long-term stress and its role in neurodevelopmental impairments in this population. Objective: To investigate potential differences between early adolescents aged 10 to 15 years with cCHD and healthy controls in physiological stress markers by hair analysis, executive function (EF) performance, and resilience. Design, Setting, and Participants: This single-center, population-based case-control study was conducted at the University Children’s Hospital Zurich, Switzerland. Patients with different types of cCHD who underwent cardiopulmonary bypass surgery during the first year of life and who did not have a genetic disorder were included in a prospective cohort study between 2004 and 2012. A total of 178 patients were eligible for assessment at ages 10 to 15 years. A control group of healthy term-born individuals was cross-sectionally recruited. Data assessment was between 2019 and 2021. Statistical analysis was performed from January to April 2023.ExposurePatients with cCHD who underwent infant open heart surgery. Main Outcomes and Measures: Physiological stress markers were quantified by summing cortisol and cortisone concentrations measured with liquid chromatography with tandem mass spectrometry in a 3-centimeter hair strand. EFs were assessed with a neuropsychological test battery to produce an age-adjusted EF summary score. Resilience was assessed with a standardized self-report questionnaire. Results: The study included 100 patients with cCHD and 104 controls between 10 and 15 years of age (mean [SD] age, 13.3 [1.3] years); 110 (53.9%) were male and 94 (46.1%) were female. When adjusting for age, sex, and parental education, patients had significantly higher sums of hair cortisol and cortisone concentrations (β, 0.28 [95% CI, 0.12 to 0.43]; P &amp;lt; .001) and lower EF scores (β, −0.36 [95% CI, −0.49 to −0.23]; P &amp;lt; .001) than controls. There was no group difference in self-reported resilience (β, −0.04 [95% CI, −0.23 to 0.12]; P = .63). A significant interaction effect between stress markers and EFs was found, indicating a stronger negative association in patients than controls (β, −0.65 [95% CI, −1.15 to −0.15]; P = .01). The contrast effects were not significant in patients (β, −0.21 [95% CI, −0.43 to −0.00]; P = .06) and controls (β, 0.09 [95% CI, −0.11 to 0.30]; P = .38). Conclusions and Relevance: This case-control study provides evidence for altered physiological stress levels in adolescents with cCHD and an association with poorer EF. These results suggest that future studies are needed to better understand the neurobiological mechanisms and timing of alterations in the stress system and its role in neurodevelopment

White matter injury in term neonates with congenital heart diseases: Topology & comparison with preterm newborns

Background: Neonates with congenital heart disease (CHD) are at high risk of punctate white matter injury (WMI) and impaired brain development. We hypothesized that WMI in CHD neonates occurs in a characteristic distribution that shares topology with preterm WMI and that lower birth gestational age (GA) is associated with larger WMI volume. Objective: (1) To quantitatively assess the volume and location of WMI in CHD neonates across three centres. (2) To compare the volume and spatial distribution of WMI between term CHD neonates and preterm neonates using lesion mapping. Methods: In 216 term born CHD neonates from three prospective cohorts (mean birth GA: 39 weeks), WMI was identified in 86 neonates (UBC: 29; UCSF: 43; UCZ: 14) on pre- and/or post-operative T1 weighted MRI. WMI was manually segmented and volumes were calculated. A standard brain template was generated. Probabilistic WMI maps (total, pre- and post-operative) were developed in this common space. Using these maps, WMI in the term CHD neonates was compared with that in preterm neonates: 58 at early-in-life (mean postmenstrual age at scan 32.2 weeks); 41 at term-equivalent age (mean postmenstrual age at scan 40.1 weeks). Results: The total WMI volumes of CHD neonates across centres did not differ (p = 0.068): UBC (median = 84.6 mm 3 , IQR = 26–174.7 mm 3 ); UCSF (median = 104 mm 3 , IQR = 44–243 mm 3 ); UCZ (median = 121 mm 3 , IQR = 68–200.8 mm 3 ). The spatial distribution of WMI in CHD neonates showed strong concordance across centres with predilection for anterior and posterior rather than central lesions. Predominance of anterior lesions was apparent on the post-operative WMI map relative to the pre-operative map. Lower GA at birth predicted an increasing volume of WMI across the full cohort (41.1 mm 3 increase of WMI per week decrease in gestational age; 95% CI 11.5–70.8; p = 0.007), when accounting for centre and heart lesion. While WMI in term CHD and preterm neonates occurs most commonly in the intermediate zone/outer subventricular zone there is a paucity of central lesions in the CHD neonates relative to preterms. Conclusions: WMI in term neonates with CHD occurs in a characteristic topology. The spatial distribution of WMI in term neonates with CHD reflects the expected maturation of pre-oligodendrocytes such that the central regions are less vulnerable than in the preterm neonates

Executive function and brain development in adolescents with severe congenital heart disease (Teen Heart Study): protocol of a prospective cohort study

INTRODUCTION Congenital heart disease (CHD) is the most frequent congenital malformation. With recent advances in medical care, the majority of patients with CHD survive into adulthood. As a result, interest has shifted towards the neurodevelopmental outcome of these patients, and particularly towards the early detection and treatment of developmental problems. A variety of mild to moderate cognitive impairments as well as emotional and behavioural problems has been observed in this population. However, a more detailed assessment of the various domains of executive function and their association with structural and functional brain development is lacking. Therefore, the current study will examine all domains of executive function and brain development in detail in a large sample of children and adolescents with CHD and healthy control children. METHODS AND ANALYSIS A total of 192 children and adolescents with CHD aged 10-15 years, who participated in prospective cohort studies at the University Children's Hospital Zurich, will be eligible for this study. As a control group, approximately 100 healthy children will be enrolled. Primary outcome measures will include executive function abilities, while secondary outcomes will consist of other neurodevelopmental measures, including intelligence, processing speed, attention, fine motor abilities and brain development. An MRI will be performed to assess structural and functional brain development. Linear regression analyses will be applied to investigate group differences and associations between executive function performance and neurodevelopmental measures. ETHICS AND DISSEMINATION This study is supported by the Swiss National Science Foundation (SNF 32003B_172914) and approved by the ethical committee of the Canton Zurich (KEK 2019-00035). Written informed consent will be obtained from all the parents and from children aged 14 years or older. Findings from this study will be published in peer-reviewed journals and presented at national and international conferences for widespread dissemination of the results

Cohort and Individual Neurodevelopmental Stability between 1 and 6 Years of Age in Children with Congenital Heart Disease

OBJECTIVE: To assess cohort and individual neurodevelopmental stability in children with congenital heart disease across childhood. STUDY DESIGN: The Reachout Study is a cohort study at the University Children's Hospital Zurich. Data from 148 children with congenital heart disease who underwent cardiopulmonary bypass surgery and 1-, 4-, and 6-year neurodevelopmental assessment were analyzed using mixed models. RESULTS: Cognitive and motor functions of the total cohort improved over time (cognitive: P = .01; motor: P <.001). The prevalence of children with cognitive impairment at age 6 years was 22.3%. Socioeconomic status showed a significant interaction with age on cognitive and motor development (cognitive: P <.001; motor: P = .001): higher socioeconomic status was associated with better neurodevelopmental outcome over time. Weight and head circumference at birth showed a significant interaction with age on motor development (weight: P = .048; head: P = .006). The correlation between test scores at different ages was weak to moderate (cognition: age 1-6 years: rho = 0.20, age 4-6 years: rho = 0.56, motor: age 1-6 years: rho = 0.23, age 4-6 years: rho = 0.50). CONCLUSIONS: Children with congenital heart disease show a mild improvement in cognitive and motor functions within the first 6 years of life, particularly those with higher socioeconomic status and larger head circumference and weight at birth. However, individual stability is moderate at best. Therefore, follow-up assessments are crucial to target therapeutic intervention effectively

Acute care delivery to persons with cognitive impairment: a mixed method study of health professionals’ care provision and associated challenges

Objectives: Cognitive impairment is common among older persons admitted to hospital and associated with adverse outcomes. Inadequate care has been widely reported, with health professionals tending to be ill-equipped to meet the specific needs of this patient group. This study aimed to investigate health professionals’ care provision to persons with cognitive impairment and associated challenges. Design and Setting: A concurrent, cross-sectional mixed method study was conducted at two university-affiliated hospitals. Participants: A total of 339 health professionals participated in the study. Measurements: An online survey (n = 312) determined the extent to which health professionals perceived their care provision to be person-centered and evidence-based (POPAC-R), and experience distress in looking after this patient group (NPI-D). Four focus group interviews (n = 27) explored health professionals’ experience of care provision. Results: More than half of the health professionals reported to act always or very frequently in person-centered and evidence-based ways, and two third experienced challenging behaviors as moderately to very distressing. Health professionals working in acute geriatric wards demonstrated statistically significant higher levels of person-centered and evidence-based care provision, and lower distress. Their caring practices pertained to building a relationship, addressing specific needs, involving family members, and working collaboratively. Conclusions: Findings suggest that geriatric models of care delivery support staff in meeting the needs of persons with cognitive impairment. Health professionals require an acute care culture that values relational, collaborative and coordinated care as essential to patient safety and quality of care, and supports the consistent implementation of evidence-based practices for this patient group