There is a high prevalence of cognitive impairment in dialysis patients. The prevalence of cognitive impairment after kidney transplantation is unknown. Study Design: Cross-sectional study. Setting and Participants: Single center study of prevalent kidney transplant recipients from a transplant clinic in a large academic center. Intervention: Assessment of cognition using the Montreal Cognitive Assessment (MoCA). Demographic and clinical variables associated with cognitive impairment were also examined. Outcomes and Measurements: a) Prevalence of cognitive impairment defined by a MoCA score of <26. b) Multivariable linear and logistic regression to examine the association of demographic and clinical factors with cognitive impairment. Data from 226 patients were analyzed. Mean (SD) age was 54 (13.4) years, 73% were white, 60% were male, 37% had diabetes, 58% had an education level of college or above, and the mean (SD) time since kidney transplant was 3.4 (4.1) years. The prevalence of cognitive impairment was 58.0%. Multivariable linear regression demonstrated that older age, male gender and absence of diabetes were associated with lower MoCA scores (p < 0.01 for all). Estimated glomerular filtration rate (eGFR) was not associated with level of cognition. The logistic regression analysis confirmed the association of older age with cognitive impairment. Cognitive impairment is common in prevalent kidney transplant recipients, at a younger age compared to general population, and is associated with certain demographic variables, but not level of eGFR.

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.

Purpose Pathogenic variants in the chromatin organizer CTCF were previously reported in seven individuals with a neurodevelopmental disorder (NDD). Methods Through international collaboration we collected data from 39 subjects with variants in CTCF. We performed transcriptome analysis on RNA from blood samples and utilized Drosophila melanogaster to investigate the impact of Ctcf dosage alteration on nervous system development and function. Results The individuals in our cohort carried 2 deletions, 8 likely gene-disruptive, 2 splice-site, and 20 different missense variants, most of them de novo. Two cases were familial. The associated phenotype was of variable severity extending from mild developmental delay or normal IQ to severe intellectual disability. Feeding difficulties and behavioral abnormalities were common, and variable other findings including growth restriction and cardiac defects were observed. RNA-sequencing in five individuals identified 3828 deregulated genes enriched for known NDD genes and biological processes such as transcriptional regulation. Ctcf dosage alteration in Drosophila resulted in impaired gross neurological functioning and learning and memory deficits. Conclusion We significantly broaden the mutational and clinical spectrum ofCTCF-associated NDDs. Our data shed light onto the functional role of CTCF by identifying deregulated genes and show that Ctcf alterations result in nervous system defects in Drosophila.

Background and objectives Cognitive impairment is common in patients with kidney disease and can affect physicians’ perception and/or patients’ ability to complete the pretransplant evaluation. We examined whether cognitive impairment influences the likelihood for transplant listing and whether patients with cognitive impairment take longer to be listed. Design, setting, participants, & measurements We conducted a single-center longitudinal cohort study. Patients presenting for their index kidney transplant evaluation were screened for cognitive impairment using the Montreal Cognitive Assessment. A score <26 indicated cognitive impairment. The transplant selection committee was blinded to the scores. Kaplan–Meier analysis assessed time to active listing by level of cognition. A Cox proportional hazards model that included age, sex, race/ethnicity, smoking, coronary artery disease, and diabetes was constructed to evaluate the association between Montreal Cognitive Assessment score and listing for transplant. Results In total, 349 patients who underwent Montreal Cognitive Assessment testing at their initial visit were included in the analysis. Patients with cognitive impairment were more likely to be older, black, and smokers. The time to listing in patients with cognitive impairment was longer than the time to listing in those with no cognitive impairment (median time, 10.6 versus 6.3 months; log rank test P=0.01). Cognitive impairment was independently associated with a lower likelihood of being listed for transplant (hazard ratio, 0.93 per unit lower Montreal Cognitive Assessment score; 95% confidence interval, 0.88 to 0.99; P=0.02). A lower proportion of patients with cognitive impairment were listed compared with patients without cognitive impairment at 1 month (2% versus 11%), 6 months (17% versus 37%), and 1 year (23% versus 41%), (P<0.001 for all). Conclusions Cognitive impairment is associated with a lower likelihood of being listed for kidney transplant, and is associated with longer time to transplant listing. Visual Abstract

Significance Statement: Kidney disease is accompanied by structural and physiologic brain abnormalities and increased risk of dementia and stroke. Because RRT with dialysis does not normalize these brain abnormalities, the authors evaluated the possible benefit of kidney transplantation. Using magnetic resonance imaging methods to measure brain abnormalities before and after kidney transplantation, they demonstrated that this intervention normalizes cerebral blood flow, neurochemical concentrations, and white matter integrity. They also found that these changes persist beyond the initial post-transplantation period and thus, cannot be attributed to periprocedural interventions, such as steroids. Their findings suggest that brain abnormalities in kidney disease may be reversible. Further studies are needed to understand the mechanisms underlying these brain abnormalities and to explore interventions to prevent and mitigate them in patients who cannot undergo kidney transplantation. Background: CKD is associated with abnormalities in cerebral blood flow, cerebral neurochemical concentrations, and white matter integrity. Each of these is associated with adverse clinical consequences in the non-CKD population, which may explain the high prevalence of dementia and stroke in ESKD. Because cognition improves after kidney transplantation, comparing these brain abnormalities before and after kidney transplantation may identify potential reversibility in ESKD-associated brain abnormalities. Methods: In this study of patients with ESKD and age-matched healthy controls, we used arterial spin labeling to assess the effects of kidney transplantation on cerebral blood flow and magnetic resonance spectroscopic imaging to measure cerebral neurochemical concentrations (N-acetylaspartate, choline, glutamate, glutamine, myo-inositol, and total creatine). We also assessed white matter integrity measured by fractional anisotropy (FA) and mean diffusivity (MD) with diffusion tensor imaging. We used a linear mixed model analysis to compare longitudinal, repeated brain magnetic resonance imaging measurements before, 3 months after, and 12 months after transplantation and compared these findings with those of healthy controls. Results: Study participants included 29 patients with ESKD and 19 controls; 22 patients completed post-transplant magnetic resonance imaging. Cerebral blood flow, which was higher in patients pretransplant compared with controls (P=0.003), decreased post-transplant (P<0.001) to values in controls. Concentrations of neurochemicals choline and myo-inositol that were higher pretransplant compared with controls (P=0.001 and P<0.001, respectively) also normalized post-transplant (P<0.001 and P<0.001, respectively). FA increased (P=0.001) and MD decreased (P<0.001) post-transplant. Conclusions: Certain brain abnormalities in CKD are reversible and normalize with kidney transplantation. Further studies are needed to understand the mechanisms underlying these brain abnormalities and to explore interventions to mitigate them even in patients who cannot be transplanted. Clinical Trial registry name and registration number: Cognitive Impairment and Imaging Correlates in End Stage Renal Disease, NCT01883349

Objectives To systematically analyse the effect of pharmacological treatment of hypertension (HTN) on cognitive decline in older adults. Methods Randomised, placebo-controlled trials with a prespecified quantitative outcome of cognition and a pharmacological intervention for at least 12 months to treat HTN in older adults (>60 years). Our primary outcome was change in cognition with pharmacological treatment of HTN. Standardised mean difference (SMD) was used to analyse different outcomes reported in the selected studies. We searched PubMed CENTRAL and the Cochrane Library from inception to 6 July 2020. Two independent reviewers assessed trial quality and extracted data. Internal and external validity of the studies was assessed. Results Nine randomised controlled trials with 34 994 participants were included in the final analysis. The net SMD for change in cognition was −0.049 (CI: −0.078 to −0.019) indicating that treatment of HTN decreased cognitive decline. Heterogeneity was low with an I² of 6%. Discussion Current evidence does not indicate worsening of cognition with treatment of HTN. Treatment of HTN in older adults may reduce cognitive decline. These results have important implications in clinical management of patients at risk for dementia. PROSPERO registration number CRD42020139750.