Purpose To investigate the pathophysiologic effects of chronic kidney disease (CKD) on brain function in children with CKD by correlating cerebral blood flow (CBF) with clinical and behavioral ...indexes. Materials and Methods In this prospective study, 73 pediatric patients with CKD (mean age, 15.80 years ± 3.63; range, 9-25 years) and 57 control subjects (mean age, 15.65 years ± 3.76; range, 9-25 years) were recruited. CBF measurements were acquired with an MRI arterial spin labeling scheme. Neurocognitive measurements were performed with traditional and computerized neurocognitive batteries. Clinical data were also collected. Group-level global and regional CBF differences between patients with CKD and control subjects were assessed. Regression analyses were conducted to evaluate the associations among regional CBF, clinical variables, and cognitive performance. Results Patients with CKD showed higher global CBF compared with control subjects that was attributable to reduced hematocrit level (mean, 60.2 mL/100 g/min ± 9.0 vs 56.5 mL/100 g/min ± 8.0, respectively). White matter CBF showed correlation with blood pressure (r = 0.244, P = .039), a finding suggestive of altered cerebrovascular autoregulation. Regional CBF differences between patients and control subjects included regions in the "default mode" network. In patients with CKD, positive extrema in the precuneus showed a strong correlation with executive function (ρ = 0.608, P = .001). Conclusion Systemic effects of estimated glomerular filtration rate, hematocrit level, and blood pressure on CBF and alterations in regional CBF may reflect impaired brain function underlying neurocognitive symptoms in CKD. These findings further characterize the nature of alterations in brain physiologic features in children, adolescents, and young adults with CKD.
Background
Depression affects 7–35% of children with chronic kidney disease (CKD), and in adults with CKD, the presence of depression links to poorer medical outcomes, social functioning ...difficulties, and neurocognitive impairments. The relationship between depression and neurocognitive function in youth with CKD is unclear. We sought to identify factors associated with depression in youth with CKD and to determine whether depression affects neurocognitive performance.
Methods
We conducted cross-sectional analyses in 71 CKD and 64 control participants aged 8 to 25 years who completed depression inventories and neurocognitive assessments as part of the Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults with CKD Study. In the CKD group, multivariable logistic regression analysis determined associations between clinical and demographic factors and depression. In the full study cohort, multivariable linear regression analyses, including an interaction term between CKD status and depression evaluated the effect of depression on 11 neurocognitive outcome domains.
Results
Obesity significantly associated with depression in the CKD group (OR 10.25,
P
= 0.01). In adjusted analyses, depressed youth with CKD scored worse than non-depressed CKD participants by 0.6–1.0 standard deviations in 5 neurocognitive domains: attention, visual memory, visual-spatial, visual working memory, and problem solving.
Conclusions
CKD youth with obesity are more likely to be depressed, and those who are depressed exhibit worse neurocognitive performance. Depression may represent a therapeutic target to improve neurocognitive performance in youth with CKD.
Abstract
Study Objectives
Obstructive sleep apnea is associated with neurobehavioral dysfunction, but the relationship between disease severity as measured by the apnea-hypopnea index and ...neurobehavioral morbidity is unclear. The objective of our study is to compare the neurobehavioral morbidity of mild sleep-disordered breathing versus obstructive sleep apnea.
Methods
Children 3–12 years old recruited for mild sleep-disordered breathing (snoring with obstructive apnea-hypopnea index < 3) into the Pediatric Adenotonsillectomy Trial for Snoring were compared to children 5–9 years old recruited for obstructive sleep apnea (obstructive apnea-hypopnea 2–30) into the Childhood Adenotonsillectomy Trial. Baseline demographic, polysomnographic, and neurobehavioral outcomes were compared using univariable and multivariable analysis.
Results
The sample included 453 participants with obstructive sleep apnea (median obstructive apnea-hypopnea index 5.7) and 459 participants with mild sleep-disordered breathing (median obstructive apnea-hypopnea index 0.5). By polysomnography, participants with obstructive sleep apnea had poorer sleep efficiency and more arousals. Children with mild sleep-disordered breathing had more abnormal executive function scores (adjusted odds ratio 1.96, 95% CI 1.30–2.94) compared to children with obstructive sleep apnea. There were also elevated Conners scores for inattention (adjusted odds ratio 3.16, CI 1.98–5.02) and hyperactivity (adjusted odds ratio 2.82, CI 1.83–4.34) in children recruited for mild sleep-disordered breathing.
Conclusions
Abnormal executive function, inattention, and hyperactivity were more common in symptomatic children recruited into a trial for mild sleep-disordered breathing compared to children recruited into a trial for obstructive sleep apnea. Young, snoring children with only minimally elevated apnea-hypopnea levels may still be at risk for deficits in executive function and attention.
Trial Registration
Pediatric Adenotonsillectomy for Snoring (PATS), NCT02562040; Childhood Adenotonsillectomy Trial (CHAT), NCT00560859
Background: Adverse health effects of cadmium in adults are well documented, but little is known about the neuropsychological effects of cadmium in children, and no studies of cadmium and blood ...pressure in children have been conducted. Objective: We examined the potential effects of low-level cadmium exposure on intelligence quotient, neuropsychological functions, behavior, and blood pressure among children, using blood cadmium as a measure of exposure. Methods: We used the data from a multicenter randomized clinical trial of lead-exposed children and analyzed blood cadmium concentrations using the whole blood samples collected when children were 2 years of age. We compared neuropsychological and behavioral scores at 2, 5, and 7 years of age by cadmium level and analyzed the relationship between blood cadmium levels at 2 years of age and systolic and diastolic blood pressure at 2, 5, and 7 years of age. Results: The average cadmium concentration of these children was 0.21 µg/L, lower than for adults in the National Health and Nutrition Examination Survey (NHANES), but comparable to concentrations in children < 3 years of age in NHANES. Except for the California Verbal Learning Test for Children, there were no differences in test scores among children in different cadmium categories. For children with detectable pretreatment blood cadmium, after adjusting for a variety of covariates, general linear model analyses showed that at none of the three age points was the coefficient of cadmium on Mental Development Index or IQ statistically significant. Spline regression analysis suggested that behavioral problem scores at 5 and 7 years of age tended to increase with increasing blood cadmium, but the trend was not significant. We found no significant associations between blood cadmium levels and blood pressure. Conclusion: We found no significant associations between background blood cadmium levels at 2 years of age and neurodevelopmental end points and blood pressure at 2, 5, and 7 years of age. The neuropsychological or hypertensive effects from longer background exposures to cadmium need further study.
Obstructive sleep apnea is associated with neurobehavioral dysfunction, but the relationship between disease severity as measured by the apnea-hypopnea index and neurobehavioral morbidity is unclear. ...The objective of our study is to compare the neurobehavioral morbidity of mild sleep-disordered breathing versus obstructive sleep apnea.
Children 3-12 years old recruited for mild sleep-disordered breathing (snoring with obstructive apnea-hypopnea index < 3) into the Pediatric Adenotonsillectomy Trial for Snoring were compared to children 5-9 years old recruited for obstructive sleep apnea (obstructive apnea-hypopnea 2-30) into the Childhood Adenotonsillectomy Trial. Baseline demographic, polysomnographic, and neurobehavioral outcomes were compared using univariable and multivariable analysis.
The sample included 453 participants with obstructive sleep apnea (median obstructive apnea-hypopnea index 5.7) and 459 participants with mild sleep-disordered breathing (median obstructive apnea-hypopnea index 0.5). By polysomnography, participants with obstructive sleep apnea had poorer sleep efficiency and more arousals. Children with mild sleep-disordered breathing had more abnormal executive function scores (adjusted odds ratio 1.96, 95% CI 1.30-2.94) compared to children with obstructive sleep apnea. There were also elevated Conners scores for inattention (adjusted odds ratio 3.16, CI 1.98-5.02) and hyperactivity (adjusted odds ratio 2.82, CI 1.83-4.34) in children recruited for mild sleep-disordered breathing.
Abnormal executive function, inattention, and hyperactivity were more common in symptomatic children recruited into a trial for mild sleep-disordered breathing compared to children recruited into a trial for obstructive sleep apnea. Young, snoring children with only minimally elevated apnea-hypopnea levels may still be at risk for deficits in executive function and attention.
Pediatric Adenotonsillectomy for Snoring (PATS), NCT02562040; Childhood Adenotonsillectomy Trial (CHAT), NCT00560859.
Depressive symptoms following adenotonsillectomy (AT) relative to controls were examined in children with obstructive sleep apnea syndrome (OSAS).
The Childhood Adenotonsillectomy Trial (CHAT) ...multisite study examined the impact of AT in 453 children aged 5 to 9.9 years with polysomnographic evidence of OSAS without prolonged desaturation, randomized to early adenotonsillectomy (eAT) or watchful waiting with supportive care (WWSC). One hundred seventy-six children (eAT n = 83; WWSC n = 93) with complete evaluations for depressive symptomatology between baseline and after a 7-month intervention period were included in this secondary analysis.
Exact binomial test assessed proportion of depressive symptomatology relative to norms, while effects of AT and OSAS resolution were assessed through linear quantile mixed-models. Treatment group assignment did not significantly impact depression symptoms, although self-reported depression symptoms improved over time (p < 0.001). Resolution of OSAS symptoms demonstrated a small interaction effect in an unexpected direction, with more improvement in parent ratings of anxious/depressed symptoms for children without resolution (p = 0.030). Black children reported more severe depressive symptoms (p = 0.026) and parents of overweight/obese children reported more withdrawn/depressed symptoms (p = 0.004). Desaturation nadir during sleep was associated with self-report depressed (r = -0.17, p = 0.028), parent-reported anxious/depressed (r = -0.15, p = 0.049), and withdrawn/depressed (r = -0.24, p = 0.002) symptoms.
Increased risk for depressed and withdrawn/depressed symptoms was detected among children with OSAS, and different demographic variables contributed to risk in self-reported and parent-reported depression symptoms. Arterial oxygen desaturation nadir during sleep was strongly associated with depressed symptoms. However, despite improvements in child-reported depressed symptoms over time, changes were unrelated to either treatment group or OSAS resolution status.
Childhood Adenotonsillectomy Study for Children with OSAS (CHAT), https://clinicaltrials.gov/show/NCT00560859, NCT00560859.
Caregivers frequently report poor quality of life (QOL) in children with sleep-disordered breathing (SDB). Our objective is to assess the correlation between caregiver- and child-reported QOL in ...children with mild SDB and identify factors associated with differences between caregiver and child report.
Analysis of baseline data from a multi-institutional randomized trial SETTING: Pediatric Adenotonsillectomy Trial for Snoring, where children with mild SDB (obstructive apnea-hypopnea index <3) were randomized to observation or adenotonsillectomy.
The Pediatric Quality of Life Inventory (PedsQL) assessed baseline global QOL in participating children 5 to 12 years old and their caregivers. Caregiver and child scores were compared. Multivariable regression assessed whether clinical factors were associated with differences between caregiver and child report.
PedsQL scores were available for 309 families (mean child age, 7.0 years). The mean caregiver-reported PedsQL score was higher at 75.2 (indicating better QOL) than the mean child-reported score of 67.9 (P < .001). The agreement between caregiver and child total PedsQL scores was poor, with intraclass correlation coefficients of 0.03 (95% CI, -0.09 to 0.15) for children 5 to 7 years old and 0.21 (95% CI, 0.03-0.38) for children 8 to 12 years old. Higher child age and health literacy were associated with closer agreement between caregiver and child report.
Caregiver- and child-reported global QOL in children with SDB was weakly correlated, more so for young children. In pediatric SDB, child-perceived QOL may be poorer than that reported by caregivers. Further research is needed to assess whether similar trends exist for disease-specific QOL metrics.
Neurocognitive problems in CKD are well documented; time-efficient methods are needed to assess neurocognition in this population. We performed the first study of the efficient 1-hour Penn ...Computerized Neurocognitive Battery (CNB) in children and young adults with CKD.
We administered the Penn CNB cross-sectionally to individuals aged 8-25 years with stage 2-5 CKD (n=92, enrolled from three academic nephrology practices from 2011 to 2014) and matched healthy controls (n=69). We analyzed results from 12 tests in four domains: executive control, episodic memory, complex cognition, and social cognition. All tests measure accuracy and speed; we converted raw scores to age-specific z-scores on the basis of Philadelphia Neurodevelopmental Cohort (n=1790) norms. We analyzed each test in a linear regression with accuracy and speed z-scores as dependent variables and with (1) CKD versus control or (2) eGFR as explanatory variables, adjusted for race, sex, and maternal education.
Patients with CKD (mean±SD eGFR, 48±25 ml/min per 1.73 m(2); mean age, 16.3±3.9 years) and controls (mean eGFR, 98±20 ml/min per 1.73 m(2); mean age, 16.0±4.0 years) were similar demographically. CKD participants had lower accuracy than controls in tests of complex cognition, with moderate to large effect sizes: -0.53 (95% confidence interval 95% CI, -0.87 to -0.19) for verbal reasoning, -0.52 (95% CI, -0.83 to -0.22) for nonverbal reasoning, and -0.64 (95% CI, -0.99 to -0.29) for spatial processing. For attention, patients with CKD had lower accuracy (effect size, -0.35 95% CI, -0.67 to -0.03) but faster response times (effect size, 0.44 95% CI, 0.04 to 0.83) than controls, perhaps reflecting greater impulsivity. Lower eGFR was associated with lower accuracy for complex cognition, facial and visual memory, and emotion identification tests.
CKD is associated with lower accuracy in tests of complex cognition, attention, memory, and emotion identification, which related to eGFR. These findings are consistent with traditional neurocognitive testing in previous studies.
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