<p>An increasing amount of literature has indicated that chronic kidney disease (CKD) is associated with cognitive deficits that increase with worsening disease severity. Although abnormalities in brain structure have been widely documented, few studies to date have examined the functioning of brain areas associated with the specific cognitive domains affected by CKD (namely, attention and executive functions). Furthermore, few studies have examined functional connectivity among CKD youth who are relatively early in the course of the disease. The present study used functional magnetic resonance imaging to examine the resting state connectivity in 67 youth with CKD (mean age, 17 y) and 58 age-matched healthy controls. Using seed-based multiple regression, decreased connectivity was observed within the anterior cingulate portion of the default mode network. In addition, decreased connectivity within the dorsolateral prefrontal cortex, paracingulate gyrus, and frontal pole were correlated significantly with disease severity. These data indicate that connectivity deficits in circuits implementing attentional processes may represent an early marker for cognitive decline in CKD.</p>

<p><strong>BACKGROUND: </strong>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.</p>

<p><strong>METHODS: </strong>We conducted cross-sectional analyses in 71 CKD and 64 control participants aged 8 to 25&nbsp;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.</p>

<p><strong>RESULTS: </strong>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.</p>

<p><strong>CONCLUSIONS: </strong>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.</p>