Cognitive Function and White Matter Changes Associated with Renal Transplantation

Abstract

Background: End-stage renal disease (ESRD) is a disease with an aging population and a high prevalence of cognitive impairment affecting quality of life, health care costs and mortality. Structural changes in the brain with decreased white matter integrity have been observed in ESRD. Understanding the changes in cognition and associated changes in brain structure after renal transplantation can help define the mechanisms underlying cognitive impairment in ESRD. Methods: We conducted a prospective, observational cohort study in ESRD patients listed for renal transplantation and followed them post-transplantation. We assessed their cognitive function with a battery of neuropsychological tests and brain white matter integrity with diffusion tensor imaging (DTI) both before transplant and 3 months after transplant. Results: Eleven patients, aged 56.5 ± 10.7 years, completed the study. Cognitive measures of memory and executive function improved after the transplant, specifically on tests of logical memory I (p = 0.004), logical memory II (p = 0.003) and digit symbol (p < 0.0001). DTI metrics also improved post the transplant with an increase in fractional anisotropy (p = 0.01) and decrease in mean diffusivity (p = 0.004). These changes were more prominent in tracts associated with memory and executive function. Conclusions: Cognitive function, particularly memory and executive function, improve post the transplant with concurrent improvements in white matter integrity in tracts associated with memory and executive function. These data suggest that abnormalities in cognition and brain structure seen in the ESRD population are at least partially reversible.

Brain Imaging and Cognition after Kidney Transplantation

“…Notably, this measured improvement in cognition was sustained at 1 year although not exceeding the improvements noted at 3 months post-transplant [9] . Furthermore, the findings noted on DTI could not have been explained by conventional MRI findings [9] . The reader is also directed to a recent study on kidney transplant recipients reported by Zhang et al [10] where the authors examined brain imaging and the default mode network (DMN) that subserves core processes of human cognition such as cognitive and emotional processing, monitoring of the surrounding environment and mind wandering.…”

“…Neuropsychologic parameters of memory and executive function improved significantly post-transplantation. These improvements in neuropsychologic tests were paralleled by significant improvements in the DTI metrics, FA and MD in tracts connecting areas associated with memory and executive function, that is, the corpus callosum, cingulate gyrus, forceps minor and forceps major [9] . Notably, this measured improvement in cognition was sustained at 1 year although not exceeding the improvements noted at 3 months post-transplant [9] .…”

“…These improvements in neuropsychologic tests were paralleled by significant improvements in the DTI metrics, FA and MD in tracts connecting areas associated with memory and executive function, that is, the corpus callosum, cingulate gyrus, forceps minor and forceps major [9] . Notably, this measured improvement in cognition was sustained at 1 year although not exceeding the improvements noted at 3 months post-transplant [9] . Furthermore, the findings noted on DTI could not have been explained by conventional MRI findings [9] .…”

“…In this issue of the Journal, Gupta et al [9] describe structure-function relationships underlying cognition, pre and post-transplantation, among a small group of kidney transplant recipients on conventional calcineurin inhibitor-based immunosuppression. In their study, neuropsychologic tests of executive function and memory and DTI were evaluated before and 90 days after A growing body of evidence points towards cognitive deficits among patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) [1][2][3] .…”

“…These 2 studies differ in several respects. Zhang et al [10] included healthy controls and yet only chose to examine 4 tracts that were chosen for convenience, whereas, Gupta et al [9] examined 13 tracts. The patients in the Zhang study were younger averaging 32 years of age, whereas the patients in the Gupta study were older averaging 56 years of age [9,10] .…”