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Regional Cerebral Blood Flow in Children and Young Adults with Chronic Kidney Disease.

ABSTRACT: 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.

SUBMITTER: Liu HS

PROVIDER: S-EPMC6102080 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Intraindividual variability (IIV) across neuropsychological measures within a single testing session is a promising marker predictive of cognitive decline and development of Alzheimer's disease (AD). We have previously shown that greater IIV is cross-sectionally associated with reduced cerebral blood flow (CBF), but not with cortical thickness or brain volume, in older adults without dementia who were amyloid beta (Aβ) positive. However, there is little known about the association between change in IIV and CBF over time. Therefore, we examined 12-month longitudinal change in IIV and interactions of IIV and AD biomarker status on changes in regional CBF. Fifty-three non-demented Alzheimer's Disease Neuroimaging Initiative (ADNI) participants underwent lumbar puncture to obtain cerebrospinal fluid (CSF) at baseline and neuropsychological testing and magnetic resonance imaging (MRI) exams at baseline and 12-month follow-up evaluation. IIV was calculated as the intraindividual standard deviation across 6 demographically-corrected neuropsychological measures. Pulsed arterial spin labeling (ASL) MRI was acquired to quantify CBF and FreeSurfer-derived a priori CBF regions of interest (ROIs) were examined. AD biomarker positivity was determined using a published CSF p-tau/Aβ ratio cut-score. Change scores were calculated for IIV, CBF, and mean neuropsychological performance from baseline to 12 months. Hierarchical linear regression models showed that after adjusting for age and gender, there was a significant interaction between IIV change and biomarker-positivity (p-tau/Aβ+) for change in entorhinal and hippocampal CBF but not for the other ROIs. Specifically, increases in IIV were associated with reductions in entorhinal and hippocampal CBF among individuals who were biomarker-positive (n = 21). In contrast, there were no significant associations between change in IIV and CBF among those who were biomarker-negative (n = 32). Findings remained similar when analyses were performed adjusting for change in mean level of neuropsychological performance. Changes in IIV may be sensitive to changes in regional hypoperfusion in AD-vulnerable regions among AD biomarker-positive individuals, above and beyond demographics and mean neuropsychological performance. These findings provide further evidence supporting IIV as a potential marker of cerebrovascular brain changes in individuals at risk for dementia.

Project description:Regional cerebral blood flow (CBF) has a complex relationship with cognitive functioning such that cognitively unimpaired individuals at risk for Alzheimer's disease (AD) may show regional hyperperfusion, while those with cognitive impairment typically show hypoperfusion. Diabetes and word-list intrusion errors are both linked to greater risk of cognitive decline and dementia. Our study examined associations between fasting blood glucose, word-list intrusion errors, and regional CBF. 113 cognitively unimpaired older adults had arterial spin labeling MRI to measure CBF in a priori AD vulnerable regions: medial temporal lobe (MTL), inferior parietal lobe (IPL), precuneus, medial orbitofrontal cortex (mOFC), and pericalcarine (control region). Hierarchical linear regressions, adjusting for demographics, vascular risk, and reference CBF region, examined the main effect of blood glucose on regional CBF as well as whether intrusions moderated this relationship. Higher glucose was associated with higher CBF in the precuneus (β = .134, 95% CI = .007 to .261, p = .039), IPL (β = .173, 95% CI = .072 to .276, p = .001), and mOFC (β = .182, 95% CI = .047 to .320, p = .009). There was no main effect of intrusions on CBF across regions. However, the glucose x intrusions interaction was significant such that having higher glucose levels and more intrusion errors was associated with reduced CBF in the MTL (β = -.186, 95% CI = -.334 to -.040, p = .013) and precuneus (β = -.146, 95% CI = -.273 to -.022, p = .022). These findings may reflect early neurovascular dysregulation, whereby higher CBF is needed to maintain unimpaired cognition in individuals with higher glucose levels. However, lower regional CBF in unimpaired participants with both higher glucose and more intrusions suggests a failure in this early compensatory mechanism that may signal a decrease in neural activity in AD vulnerable regions.

Project description:To characterize the distribution of blood pressure (BP), prevalence, and risk factors for hypertension in pediatric chronic kidney disease, we conducted a cross-sectional analysis of baseline BPs in 432 children (mean age 11 years; 60% male; mean glomerular filtration rate 44 mL/min per 1.73 m(2)) enrolled in the Chronic Kidney Disease in Children cohort study. BPs were obtained using an aneroid sphygmomanometer. Glomerular filtration rate was measured by iohexol disappearance. Elevated BP was defined as BP >or=90th percentile for age, gender, and height. Hypertension was defined as BP >or=95th percentile or as self-reported hypertension plus current treatment with antihypertensive medications. For systolic BP, 14% were hypertensive and 11% were prehypertensive (BP 90th to 95th percentile); 68% of subjects with elevated systolic BP were taking antihypertensive medications. For diastolic BP, 14% were hypertensive and 9% were prehypertensive; 53% of subjects with elevated diastolic BP were taking antihypertensive medications. Fifty-four percent of subjects had either systolic or diastolic BP >or=95th percentile or a history of hypertension plus current antihypertensive use. Characteristics associated with elevated BP included black race, shorter duration of chronic kidney disease, absence of antihypertensive medication use, and elevated serum potassium. Among subjects receiving antihypertensive treatment, uncontrolled BP was associated with male sex, shorter chronic kidney disease duration, and absence of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use. Thirty-seven percent of children with chronic kidney disease had either elevated systolic or diastolic BP, and 39% of these were not receiving antihypertensives, indicating that hypertension in pediatric chronic kidney disease may be frequently under- or even untreated. Treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may improve BP control in these patients.

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Regional Cerebral Blood Flow in Children and Young Adults with Chronic Kidney Disease.

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