Altered white matter microstructure mediates the relationship between hemoglobin levels and cognitive control deficits in end‐stage renal disease patients

Abstract

The brain-kidney crosstalk theory suggested that the brain and kidneys may be considered end organs on parallel trajectories and subject to shared risk factors, which are receiving increasing attention. Cognitive control deficits were frequently presented in patients with end-stage renal disease (ESRD). Whether or not cognitive control impairment is concerned with brain-kidney crosstalk is in need of further research. To detect the relationship between ESRD and cognitive control impairment, diffusion tensor imaging was collected in 64 healthy controls (HCs) and 64 patients with ESRD. Tract-based spatial statistics and fixel-based analysis were used to detect the difference of white matter (WM) microstructure and morphology between ESRD patients and HCs in the whole brain. Tractography atlas-based analysis was also used to investigate the difference of diffusional characteristics along fiber bundles of interest between the two groups. For the whole-brain analysis, ESRD patients showed WM microstructural alteration and fiber density variation in the cingulum. In addition, ESRD patients exhibited higher MD and RD than HCs along the anterior cingulum. Among all of the blood biochemistry tests that represent kidney disease to a degree, the stepwise regression analysis showed that only hemoglobin significantly contributed to the cognitive control deficits in ESRD patients. Mediation analysis proved that the relationship between hemoglobin and cognitive control deficits of ESRD patients was mediated by WM microstructural alteration of the cingulum. Our results indicated that the anterior cingulum was correlated with cognitive control deficits and mediated the impact of hemoglobin on cognitive control.

How Do You Feel Now? The Salience Network Functional Connectivity in End-Stage Renal Disease

“…One focus of this study was the SN due to its role on the brain end of the renal-brain axis. Our current findings were generally consistent with earlier reports, for example, recent studies have reported gray matter loss (Zhang et al, 2013), disrupted white matter microstructure (Mu et al, 2018a), elevated cerebral blood flow (CBF) (Jiang et al, 2016), and dysconnectivity (Mu et al, 2018b) in the SN in patients. The SN is engaged in identifying and responding to salient stimuli, as well as recruiting relevant largescale functional networks for advanced cognition (Chand and Dhamala, 2016).…”

“…Moreover, hemoglobin concentration may affect blood oxygen level-dependent (BOLD) signals, coupling with alterations of brain activity. Some research found the interaction between the elevated CBF and disrupted microstructure involving the ACC and insula, cognitive dysfunction, and low level of hemoglobin ( Jiang et al, 2016 ; Mu et al, 2018a ). So our findings may further deepen the understanding of the relationship between anemia and cognitive impairment from functional dysconnectivity within the SN.…”

“…Brain structural and functional imaging provides new insights into ESRD-related cognitive dysfunction. Structural studies reported that ESRD patients had reduced gray matter volume and white matter integrity, including the bilateral insula and anterior cingulate cortex (ACC), which was correlated with decreased kidney function and cognitive decline ( Zhang et al, 2013 ; Sedaghat et al, 2015 ; Mu et al, 2018a ). Resting-state functional connectivity (FC), in contrast, may sensitively reflect the energy demands associated with synaptic signal transmission ( Tomasi et al, 2013 ).…”

Visual dysfunction predicts cognitive impairment and white matter degeneration in Parkinson’s disease

“…All raw imaging data in our cohort were visually inspected and clinically significant cerebrovascular disease was excluded, however, due to the acquired MRI sequences, we could not systematically quantify and control for white matter hyperintensities, which could lead to fibre density reduction 48 . This is in line with other published studies using fixel-based analysis, 14,24,49,50 but future studies need to clarify the effect of white matter hyperintensities on fixel-based metrics. At both study timepoints, participants with PD underwent imaging on their usual dopaminergic medications.…”

Fixel Based Analysis Reveals Atypical White Matter Micro- and Macrostructure in Adults With Autism Spectrum Disorder: An Investigation of the Role of Biological Sex

“…Rather, FBA provides indices of microscopic fiber density (FD; intra-axonal volume, thought to reflect the density of a population of fibers within voxel), macroscopic fiber cross-section (FC; an estimate of fiber bundle diameter derived from the FD metric), and fiber density and cross-section (FDC; a combined measure of FD and FC; Raffelt D. A. et al, 2017 ). This technique has been applied to investigate WM in preterm infants (Pannek et al, 2018 ; Pecheva et al, 2019 ) and to understand WM development and function in healthy individuals (Genc et al, 2018 ; Bleker et al, 2019 ; Mizuguchi et al, 2019 ), as well as to understand WM aberration in various mental health and medical conditions (Gajamange et al, 2018 ; Grazioplene et al, 2018 ; Mito et al, 2018 ; Mu et al, 2018 ; Lyon et al, 2019 ; Dimond et al, 2019 ; Feshki et al, 2019 ).…”