Cognitive Impairment In Chronic Kidney Disease Research Articles

#3042 Prevalence and associations of impaired cognitive function for people with chronic kidney disease: baseline findings from the NURTuRE-CKD cohort study

Abstract Background and Aims Chronic kidney disease (CKD) is known to be associated with impaired cognitive function, with lower estimated glomerular filtration rate (eGFR) associated with poorer cognitive performance [1]. Though CKD prevalence increases with age, the association with cognitive disorders is not entirely explained by age distribution. Cognitive impairment in CKD is multifactorial with potential biochemical, cardiovascular, medication and socio-economic mediators. As with other long-term conditions, self-management of kidney disease becomes more difficult in the context of cognitive impairment. The prevalence and associations of cognitive impairment in people referred to secondary care with CKD is not well described. This study therefore aimed to identify the prevalence and associations of impaired cognitive function among a referred population of people with CKD. Method The NURTuRE-CKD cohort recruited 2996 people with an estimated Glomerular Filtration Rate (eGFR) of 15-59 ml/min/1.73 m2 (CKD-EPI equation) or ≥60 ml/min/1.73 m2 with a urine albumin to creatinine ratio (uACR) of more than 30 mg/mmol referred to one of 16 secondary care nephrology clinics. Baseline data were collected between 2017-2019 including sociodemographic, anthropometric, biochemical, and clinical information and included the 6-item cognitive impairment test (6-CIT), a commonly used cognitive screening instrument. Other scores collected included the Hospital Anxiety and Depression score (HADS), EQ-5D-5L as a health-related quality of life (HRQoL) measure and Single Item Literacy Screener (SILS). Prevalence of impaired cognitive function (defined as 6-CIT score of 8 or more out of 28) was calculated and multivariable mixed effects logistic regression models used to identify associations with impaired cognitive function. The multivariable model was adjusted for known factors impacting cognitive impairment and recruitment region as a random effect. Results A total of 2743/2996 (91.6%) participants had complete 6-CIT data. Median age was 66 years and 41% were female. Median eGFR was 34 ml/min/1.73 m2. Prevalence of cognitive impairment was 8.7% (240/2743), rising from 5.3% in those <65 to 10.6% in those ≥65 years. eGFR was not associated with cognitive impairment on univariate analysis. After adjustment, greater likelihood of cognitive impairment was independently associated with older age, Asian and Black ethnicity (compared to white), and limited health literacy. Lower likelihood of cognitive impairment was associated with better HRQoL and higher education attainment (Figs 1 and 2). Conclusion Cognitive impairment was relatively common in this cohort of people with CKD. Similar associations for cognitive impairment with age and education in a CKD population had also been identified in CKD-REIN—a prospective cohort of CKD patients recruited from secondary care in France, though using a different cognitive function measure. Associations of limited health literacy, ethnicity, and HRQoL with cognitive impairment were identified risk factors that could aid clinicians in recognising high risk patients to prompt screening and improve management. Follow-up data will allow longitudinal analyses to explore associations between impaired cognitive function and health-related outcomes, between kidney function and change in cognitive function and risk factors for change in cognitive function, including the role of inflammatory markers. Limitations: this analysis only used baseline data so causality cannot be established, 6-CIT is a screening rather than diagnostic tool for cognitive impairment.

Exploring Cognitive Dysfunction as a Secondary Effect of Kidney Disease: Unveiling the Kidney-Brain Interconnection. A Literature Review

Background: Chronic Kidney Disease (CKD) is increasingly recognized as a systemic condition affecting not only renal function but also various extra-renal systems, including the central nervous system. Cognitive impairment (CI) has emerged as a significant concern in CKD patients, manifesting as a spectrum ranging from mild cognitive deficits to clinically relevant dementia. Methods: A literature research of electronic databases (Pub-med library, NDT articles and Google Scholar covering the period from 2003-to March 2024) were conducted to assess the association of CKD and cognitive impairment. Results: This literature review explores the historical perspectives, definitions, clinical significance, methodological challenges, and potential mechanisms underlying CI in CKD. Furthermore, it highlights ongoing research initiatives, structural and hemodynamic similarities between the kidney and brain. Conclusions: Increasing clinician’s awareness of CI in CKD is essential to improving its early identification. Therefore, the early identification of possible precursors of CI and the diagnosis and prevention of it is of increased importance. Due to the complexity of CKD, there is tremendous need for increased multidisciplinary team for future directions in this ever-expanding area which is pivotal to our patient’s quality and quantity of life. Keywords: Cognitive impairment, chronic kidney disease, kidney-brain axis.

Cognitive impairment and the blood-brain barrier in chronic kidney disease: role of the uremic toxins

Patients with chronic kidney disease (CKD) have an increased risk of cognitive disorders, presenting as vascular dementia, compared with the general population. These cognitive disorders occur early during the course of the kidney disease and evolve in parallel with the decline in glomerular filtration rate. They affect 30 to 80% of patients with stage 5 CKD. Kidney transplantation only partially improves cognitive impairment. In this narrative review, we summarize the epidemiology and recent clinical and experimental data on cognitive impairment in CKD and discuss the potential specific mechanisms. Among the factors associated with cognitive impairment, the accumulation of uremic toxins such as indoxyl sulfate appears to be a specific risk factor for cognitive decline. These toxins have an endothelial toxicity that can disrupt the cerebral endothelium. The rupture of the blood-brain barrier (BBB) is a mechanism implicated in several neurodegenerative pathologies and systemic diseases with cerebral tropism. Recent experimental findings in CKD indicate that disruption of the BBB appears to be an important mechanism behind cognitive impairment in CKD. In murine models of CKD, increased BBB permeability is linked to memory impairment and aryl hydrocarbon receptor activation following accumulation of circulating indoxyl sulfate. This disruption of the BBB could also have harmful consequences for stroke susceptibility and drug neurotoxicity in CKD patients.

Association of Urinary Biomarkers of Renal Tubular Injury with Cognitive Dysfunction in Older Patients with Chronic Kidney Disease: A Cross-Sectional Observational Study

Epidemiological data suggest that individuals in all stages of chronic kidney disease (CKD) have higher risks of developing cognitive impairment. The relationship between CKD and cognition has been assessed exclusively using glomerular function markers; however, kidney tubule injury has not been assessed. We assessed the association between urinary biomarkers of renal tubular injury and cognitive dysfunction in older patients with CKD Stages 3-4. According to the Montreal Cognitive Assessment, participants were divided into cognitive dysfunction and control groups. Compared with the control group, the cognitive dysfunction group had significantly higher percentages of smokers, noticeably lower average education, and higher mitochondrial DNA (mtDNA) levels in the peripheral blood. Spearman correlation analysis showed that higher urine neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and beta-2 microglobulin (β2M) levels were significantly associated with lower cognitive scores. Multivariate logistic regression analysis showed that only increased urinary β2M levels were independently associated with cognitive worsening in CKD after adjusting for confounders. Logistic regression identified a promising role of urinary β2M combined with smoking and education for predicting cognitive impairment in CKD. Urinary β2M and cognitive function negatively correlated with mtDNA content, suggesting that mitochondrial dysfunction is a common pathophysiological mechanism linking CKD and cognitive dysfunction.

Insights into Cognitive Brain Health in Chronic Kidney Disease.

Cognitive impairment and Chronic Kidney Disease (CKD) are common in older adults. With advances in medicine, the average lifespan is expected to increase, further increasing the prevalence of both conditions. The mechanisms underlying cognitive impairment in CKD are unclear. While mild-moderately low estimated glomerular filtration rate (eGFR) may not be associated with cognitive impairment, severely decreased eGFR and albuminuria do. Patients on dialysis have a high prevalence of cognitive impairment. Cognitive function improves after kidney transplantation. However, some residual cognitive deficits persist after transplantation, indicating that restoring the kidney function alone may not be enough to restore cognitive function, and other etiological factors may play a role. Albuminuria, another marker of CKD is also associated with cognitive impairment. However, albuminuria is often undiagnosed. Improving early identification and management of patients with albuminuria may be a good population-based dementia prevention strategy. Other factors associated with cognitive impairment in CKD include anemia and other metabolic derangements commonly observed in CKD. In this article, we reviewed the prevalence of cognitive impairment in CKD, the potential mechanisms underlying cognitive impairment in CKD, andthecurrent evidence on the association between cognitive impairment and eGFR and albuminuria.

Cognitive Sequelae and Hippocampal Dysfunction in Chronic Kidney Disease following 5/6 Nephrectomy.

Neurological disorders are prevalent in patients with chronic kidney disease (CKD). Vascular factors and uremic toxins are involved with cognitive impairment in CKD. In addition, vascular dementia-induced alterations in the structure and function of the hippocampus can lead to deficits in hippocampal synaptic plasticity and cognitive function. However, regardless of this clinical evidence, the pathophysiology of cognitive impairment in patients with CKD is not fully understood. We used male Sprague Dawley rats and performed 5/6 nephrectomy to observe the changes in behavior, field excitatory postsynaptic potential, and immunostaining of the hippocampus following CKD progression. We measured the hippocampus volume on magnetic resonance imaging scans in the controls (n = 34) and end-stage renal disease (ESRD) hemodialysis patients (n = 42). In four cognition-related behavior assays, including novel object recognition, Y-maze, Barnes maze, and classical contextual fear conditioning, we identified deficits in spatial working memory, learning and memory, and contextual memory, as well as the ability to distinguish familiar and new objects, in the rats with CKD. Immunohistochemical staining of Na+/H+ exchanger1 was increased in the hippocampus of the CKD rat models. We performed double immunofluorescent staining for aquaporin-4 and glial fibrillary acidic protein and then verified the high coexpression in the hippocampus of the CKD rat model. Furthermore, results from recoding of the field excitatory postsynaptic potential (fEPSP) in the hippocampus showed the reduced amplitude and slope of fEPSP in the CKD rats. ESRD patients with cognitive impairment showed a significant decrease in the hippocampus volume compared with ESRD patients without cognitive impairment or the controls. Our findings suggest that uremia resulting from decreased kidney function may cause the destruction of the blood–brain barrier and hippocampus-related cognitive impairment in CKD.

Association of Proximal Tubular Secretory Clearance with Long-Term Decline in Cognitive Function.

People with chronic kidney disease (CKD) are at high risk for cognitive impairment and progressive cognitive decline. Retention of protein-bound organic solutes that are normally removed by tubular secretion is hypothesized to contribute to cognitive impairment in CKD. We followed 2362 participants who were initially free of cognitive impairment and stroke in the prospective Chronic Renal Insufficiency Cohort (CRIC) Study. We estimated tubular secretory clearance by the 24-hour kidney clearances of eight endogenous solutes that are primarily eliminated by tubular secretion. CRIC study investigators assessed participants' cognitive function annually using the Modified Mini-Mental State (3MS) Examination. Cognitive decline was defined as a sustained decrease of more than five points in the 3MS score from baseline. Using Cox regression models adjusted for potential confounders, we analyzed associations between secretory solute clearances, serum solute concentrations, and cognitive decline. The median number of follow-up 3MS examinations was six per participant. There were 247 incident cognitive decline events over a median of 9.1 years of follow-up. Lower kidney clearances of five of the eight secretory solutes (cinnamoylglycine, isovalerylglycine, kynurenic acid, pyridoxic acid, and tiglylglycine) were associated with cognitive decline after adjustment for baseline eGFR, proteinuria, and other confounding variables. Effect sizes ranged from a 17% to a 34% higher risk of cognitive decline per 50% lower clearance. In contrast, serum concentrations of the solutes were not associated with cognitive decline. Lower kidney clearances of secreted solutes are associated with incident global cognitive decline in a prospective study of CKD, independent of eGFR. Further work is needed to determine the domains of cognition most affected by decreased secretory clearance and the mechanisms of these associations.

The Intersection of SGLT2 Inhibitors, Cognitive Impairment, and CKD.

Impairment in cognition and decline in kidney function often converge in the aging individual with chronic kidney disease (CKD). Cognitive impairment (CI) may be preventable through modification of health behaviors and risk factors that contribute to the vascular disease burden. CKD patients often have multiple coexisting comorbid conditions contributing to vascular risk. These comorbidities include hypertension, diabetes, cerebrovascular disease, and cardiovascular disease. Emerging evidence suggests that the management and prevention of vascular risk factors and cardiovascular diseases may indirectly contribute to the prevention of CI in CKD. Sodium glucose transport protein 2 inhibitors (SGLT2i) are emerging as the standard of care for selected individuals with CKD, type 2 diabetes (T2DM), and heart failure with rapidly expanding indications being actively investigated. In this narrative review, we examine the intriguing hypothesis that SGLT2i demonstrate potential disease modifying properties in CI among individuals with CKD.

Intensive blood pressure control and cognitive impairment in chronic kidney disease: The jury is still out

Globally, 55 million people suffer from dementia, mainly Alzheimer's disease (60–70% of cases), and over 60% of patients live in low- or middle-income countries. This number is estimated to rise to 78 million in 2030 and 139 million in 2050, and over 70% of new cases will occur in poorer countries, with huge socioeconomic costs for affected individuals, their relatives, and governments [ [1] World Health Organization SGGlobal action plan on the public health response to dementia 2017–25. 2017; (Available at https://www.who.int/publications/i/item/global-action-plan-on-the-public-health-response-to-dementia-2017-2025 Accessed on 08/05/2022) Google Scholar ]. People with chronic kidney disease (CKD), as defined by an estimated glomerular filtration rate [eGFR] lower than 60 mL/min/1.73 m2, or eGFR ≥ 60 plus a marker of kidney damage (albuminuria, abnormal kidney ultrasound scan, etc.) [ [2] Stevens P.E. Levin A. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013; 158: 825-830 Crossref PubMed Scopus (1475) Google Scholar ] have a significantly higher risk for cognitive impairment compared to the general population [ [3] Drew D.A. Weiner D.E. Sarnak M.J. Cognitive impairment in CKD: pathophysiology, management, and prevention. American Journal of Kidney Diseases. 2019; 74: 782-790 Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar ]. As the global prevalence of CKD is as high as 13.4% (i.e. over 700 million people) [ [4] Hill N.R. Fatoba S.T. Oke J.L. Hirst J.A. O’Callaghan C.A. Lasserson D.S. et al. Global prevalence of chronic kidney disease - a systematic review and meta-analysis. PLoS ONE. 2016; 11 (e0158765-e) Crossref Scopus (1572) Google Scholar ], it is hardly surprising that there is a great interest in the primary and secondary prevention of dementia worldwide.

Mechanisms in Chronic Kidney Disease and Associated Cardiovascular Remodeling Contributes to the Progression of Cognitive Impairment in Women

IntroductionIn end‐stage chronic kidney disease (CKD) (stages 4‐5) the prevalence of cognitive impairment (CI) has been estimated at 30‐60%, twice the values observed in age‐ and sex‐matched controls. CKD is greater in females vs. males due to a higher risk of renal infections, especially during the pregnancy, which may result in the renal complications later in life, when the level of protective estrogen declines. Cardiovascular diseases (CVD) including hypertension and increased central arterial stiffness (CAS) accompany CKD development across all stages of this disease. CAS drives pulse pressure (PP) and pulsatile component index (PCI) increases and cerebral microvascular damage resulting in a reduction of blood supply to the brain hereby contributing to CI. Elevated PP and PCI are associated with higher mortality in CVD and CKD independently of BP. Moreover, PP is a cardiovascular risk factor independent on PCI in women >55 years.HypothesisThe aim of the study was to determine whether CKD potentiates development of CI due to cardiovascular remodeling and whether CI in CKD is more pronounced in women. Furthermore, this study also aimed to determine whether reduced estrogen levels in older women with CKD contribute to the progression of CI.MethodsAll research was performed in accordance with the guidelines and regulations set forth by the Declaration of Helsinki regarding the use and enrollment of human subjects in research. A total of 26 female CKD patients (age 45‐50 years and older, CKD stage 4, GFR 15‐29, and Creatinine > 1mg/dL) and 30 age and sex‐ matched healthy control patients were enrolled with exclusion criteria (history of HIV, hepatitis, malignancies, admission and/or surgery for trauma, head injury and pregnancy at time of enrollment). Blood pressure (systolic and diastolic blood pressure (SBP, DBP) was measured, clinical blood work, echocardiography (ECHO) and mini‐mental state examination (MMSE) was performed as well as levels of amyloid beta‐40 (Aβ‐40) measured. PCI was calculated as difference between peak systolic and end diastolic flow velocity, divided by the flow velocity. Estrogen levels were measured in the plasma samples. The data were analyzed by unpaired two‐tailed t‐test and Pearson correlation with P values adjusted for false discovery rate.ResultsCKD patients had higher SBP, PP, PCI, LV systolic and diastolic volume (estimated by ECHO), lower LV ejection fraction, higher plasma NT‐proBNP and AST (CVD markers), glucose, triglycerides, plasma Aβ‐40 (Alzheimer’s disease marker), BUN and creatinine (CKD markers) and lower score in MMSE vs. healthy control (p<0.05). Plasma estrogen levels were significantly lower in CKD patients which correlated with the cognitive test scores and the renal function. Cognitive test results positively correlated with LV stroke volume, negatively correlated with PCI, a measurement of pulsatility of blood pressure, and negatively correlated with plasma ASP, a marker of CVD.ConclusionHigher PP, PCI, plasma Aβ‐40 and lower levels of estrogen and lower score in MMSE in female CKD patients supports our hypothesis that cardiovascular remodeling in women with CKD contributes to the development and progression of CI.

Emotional and cognitive changes in chronic kidney disease

Chronic kidney disease (CKD) leads to cognitive impairment and emotional changes. However, the precise mechanism underlying the crosstalk between the kidneys and the nervous system is not fully understood. Inflammation and cerebrovascular disease can influence the development of depression in CKD. CKD is one of the strongest risk factors for cognitive impairment. Moreover, cognitive impairment occurs in CKD as patients experience the dysregulation of several brain functional domains due to damage caused to multiple cortical regions and to subcortical modulatory neurons. The differences in structural brain changes between CKD and non-CKD dementia may be attributable to the different mechanisms that occur in CKD. The kidney and brain have similar anatomical vascular systems, which may be susceptible to traditional risk factors. Vascular factors are assumed to be involved in the development of cognitive impairment in patients with CKD. Vascular injury induces white matter lesions, silent infarction, and microbleeds. Uremic toxins may also be directly related to cognitive impairment in CKD. Many uremic toxins, such as indoxyl sulfate, are likely to have an impact on the central nervous system. Further studies are required to identify therapeutic targets to prevent changes in the brain in patients with CKD.

Dementia associated with chronic kidney disease is accompanied by increase in plasma amyloid beta and cardiovascular dysfunction.

In end-stage chronic kidney disease (CKD) the prevalence of cognitive impairment (CI) has been estimated at 30-60%. Cardiovascular diseases (CVD) including increased central arterial stiffness (CAS) accompany CKD development. CAS drives pulse pressure (PP) and pulsatile component index (PCI) increases and cerebral microvascular damage resulting in a reduction of blood supply to the brain hereby contributing to CI. Elevated PP and PCI are associated with higher mortality in CVD and CKD independently of BP. The aim of the study was to determine whether CKD potentiates CI development due to CAS and the resultant increase in the PCI, a major contributor to brain and renal microvasculature damage. Measurements of systolic and diastolic blood pressure (SBP, DBP), echocardiography (ECHO), plasma amyloid beta-40 (Aβ-40), BUN, creatinine, aspartate aminotransferase (AST), brain natriuretic peptide (BNP), and mini-mental status examination (MMSE) were performed in 25 patients with stage IV CKD and in 22 age- and sex-matched healthy controls (Table 1). PCI was calculated as a function of SBP and DBP. The data were analyzed by unpaired two-tailed t-test, Pearson correlation with P values adjusted for false discovery rate, and are presented as mean±SEM. CKD patients had higher SBP, PP, PCI, LV systolic and diastolic volume, lower LV ejection fraction, higher plasma BNP and AST (CVD markers), plasma Aβ-40 (Alzheimer's disease marker), BUN and creatinine (CKD markers) and lower score in MMSE vs. healthy control (Table 1). Cognitive test results positively correlated with LV stroke volume, negatively correlated with PCI, a measurement of pulsatility of BP, and negatively correlated with plasma ASP, a marker of CVD (Table 2). SBP and DBP did not correlate with cognitive parameters. Further investigation of the possible metabolic role of Aβ-40 in the development of CI in CKD patients, and whether plasma AST can be a marker of CI in CKD, will be assessed in the future studies. Higher PP, PCI and lower score in MMSE in CKD patients supports our hypothesis that cardiovascular remodeling in CKD is a key component of CI progression. Supported by the NIH Grant 1R15HL150721 (K.S.), and in part by NIH/NIA Intramural Research Program.

Prevalence, types and recognition of cognitive impairment in dialysis patients in South Eastern Sydney.

In international studies, cognitive impairment is a common but underdetected issue in dialysis patients. Chronic kidney disease (CKD) shares risk factors with and is an independent risk factor for cognitive impairment. There is a lack of Australian data on cognitive impairment in this at-risk population. This has implications on service planning because cognitive impairment in CKD is associated with higher mortality, morbidity and healthcare costs. To examine the prevalence, types and clinician recognition of cognitive impairment within an Australian dialysis population. A cross-sectional study of haemodialysis and peritoneal dialysis patients in South Eastern Sydney screened for cognitive impairment using the Montreal Cognitive Assessment (MoCA). Participant interviews, medical records, physician and carer questionnaires, were used to determine the types of cognitive impairment and rate of recognition. One hundred and six participants were included (median age 66 years, median dialysis duration 2 years) and 58 (54.7%) were cognitively impaired on the MoCA, of whom old age psychiatrists sub-classified 21 (36.2%) as having dementia, and 31 (53.4%) with 'cognitive impairment, no dementia'; 36/58 (62.0%) of the cognitively impaired participants on the MoCA were suspected of having cognitive impairment by nephrologists but only 14/58 (24.1%) had this documented in medical records. Although cognitive impairment is common in dialysis patients, there are low levels of detection by clinical teams. Cognitive screening of dialysis patients should be incorporated as part of wider assessment and determination of management goals such as individuals' capacity to self-care and provide informed consent to treatments.

Impact of unilateral ureteral obstruction on cognition and neurodegeneration

IntroductionCognitive impairment is a common complication in chronic kidney disease (CKD) patients. Currently, limited types of animal models are available for studying cognitive impairment in CKD. We used unilateral ureteral obstruction (UUO) in mice as an animal model to study the cognitive changes and related pathology under prolonged renal impairment MethodsUUO was performed in 8-week-old male C57BL/6 N mice with double-ligation of their left ureter. A sham group was subjected to the same experimental procedure without ureteral obstruction. Cognitive and behavioral tests were performed to examine potential changes in cognition and behavior at 2, 4 and 12 weeks after surgery. Sera were collected, and kidneys and brains were harvested for the detection of systemic inflammation markers and neurodegenerative changes. ResultsThese mice displayed weak performance in the novel object recognition test, Y-maze test, and puzzle box test compared to the sham group. Reductions in synaptic proteins such as synapsin-1, synaptophysin, synaptotagmin, PSD95, NMDAR2B and AMPAR were confirmed by western blot analysis. Histological examination revealed elevated levels of Nrf2 and 8-hydroxyguanosine, and hyperphosphorylation of tau in the hippocampus. UUO mice also had increased levels of C-reactive protein (CRP) and TNF-α. ConclusionsWe characterized the cognitive and neuropathological changes in UUO mice. The results show that this mouse model can be used to further study cognitive changes related to chronic renal impairment.

Cognitive impairment in patients with moderate to severe chronic kidney disease: the Salford kidney cohort study.

BackgroundCognitive impairment in chronic kidney disease (CKD) is common and underrecognized [1, 2]. Determining risk factors for cognitive impairment and whether speed of CKD progression is an important consideration may help identify cognitive impairment by nephrologists. Vascular disease is thought to underpin cognitive impairment in CKD and by segregating CKD patients with proven vascular disease, we may also be able to discover other important associations with cognitive impairment in CKD patients.MethodA total of 250 patients in a UK prospective cohort of CKD patients underwent two cognitive assessments: Montreal Cognitive Assessment test and Trail Making Test. Cognitive impairment was defined using validated population cut-offs (cognitive impairment) and relative cognitive impairment. Relative cognitive impairment was defined by <1 standard deviation below the mean Z-score on any completed test. Two multivariable logistical regression models identified variables associated with cognitive impairment and realtive cognitive impairment.ResultsAbout 44 and 24.8% of patients suffered cognitive impairment and relative cognitive impairment, respectively. Depression, previous stroke and older age were significantly associated with cognitive impairment. Older age was significantly associated with relative cognitive impairment (P ≤ 0.05) and higher proteinuria and the use of psychodynamic medications were also significantly associated with relative cognitive impairment (P = 0.05). Delta estimated glomerular filtration rate (eGFR) in patients with cognitive impairment and relative cognitive impairment compared with those having normal cognition was similar (−0.77 versus −1.35 mL/min/1.73 m2/year, P = 0.34 for cognitive impairment and −1.12 versus −1.02 mL/min/1.73 m2/year, P = 0.89 for relative cognitive impairment).ConclusionRisk factors for cognitive impairment in CKD include previous stroke, depression or anxiety, higher proteinuria and prescription of psychodynamic medications. Patients with a faster eGFR decline do not represent a group of patients at increased risk of cognitive impairment.

The specific impact of uremic toxins upon cognitive domains: a review.

ABSTRACTOne of the mechanisms proposed for chronic kidney disease (CKD)-related cognitive impairment is the accumulation of uremic toxins due to the deterioration of the renal clearance function. Cognition can be categorized into five major domains according to its information processing functions: memory, attention, language, visual-spatial, and executive. We performed a review using the terms 'uric acid', 'indoxyl sulfate', 'p-cresyl sulfate', 'homocysteine', 'interleukins' and 'parathyroid hormone'. These are the compounds that were found to be strongly associated with cognitive impairment in CKD in the literature. The 26 selected articles point towards an association between higher levels of uric acid, homocysteine, and interleukin 6 with lower cognitive performance in executive, attentional, and memory domains. We also reviewed the hemodialysis effects on cognition. Hemodialysis seems to contribute to an amelioration of CKD-related encephalopathic dysfunction, although this improvement occurs more in some cognitive domains than in others.

Montreal Cognitive Assessment for cognitive assessment in chronic kidney disease: a systematic review.

Introduction:There is evidence in the literature that cognitive impairment is more prevalent in individuals with chronic kidney disease (CKD) than in the general population. The Montreal Cognitive Assessment (MoCA) is an instrument with a good application profile for cognitive evaluation of patients with CKD-like impairments. The objective of this study is to perform a systematic review of MoCA use in the context of CKD.Method:The keywords "Montreal Cognitive Assessment", "Kidney Disease" and "Chronic Kidney Disease" were used to search the databases. The inclusion criteria were: a) empirical articles; b) approach to cognitive impairment in CKD; c) papers in Portuguese and English.Results:The studies were mostly cross-sectional, published in medical journals, with research carried out mostly in Europe. About 45% of the studies had samples of less than 150 participants and variations in the prevalence of cognitive impairment were found ranging from 28.9% to 74.6%. The cutoff point for the identification of the impairment presented variation between the studies.Discussion:The results' analysis demonstrates the need for more complete studies on MoCA scoring and adaptation in its different versions. We recommend to the health professionals who will use the results in the clinical setting that the interpretation of the results be made in the light of studies more related to the context lived by the patients.Conclusions:The instrument is efficient to be used in several stages and treatment modalities of the disease. We point to the need to adapt a cut-off point for the instrument in the different translations of the instrument.

Cognitive Impairment in Chronic Kidney Disease-Prevalence, Mechanisms and Consequences

In ageing populations, chronic kidney disease (CKD) gets an increasing health problem worldwide. While current therapy of CKD mostly focusses on kidney function and cardiovascular comorbidity, cognition, which crucially influences adherence to CKD therapy, is often neglected. Prevalence of cognitive impairment is high in CKD, ranging from 17% to 87%, depending on CKD severity and cognitive domain affected. In contrast to Alzheimer’s disease patients, which often show impairment in memory function, CKD patients present with a broader spectrum of cognitive deficits, namely impairment in executive function, information processing, language and visuoconstruction which is usually mild in early CKD stages but advances with CKD progression and progression of comorbidities. Mechanisms underlying cognitive impairment in CKD are discussed and conclusions are derived how cognitive impairment may be prevented in CKD and, if cognitive deficits are present, how cognitive impairment may be taken into consideration in patient management.

Association of Kidney Function Biomarkers with Brain MRI Findings: The BRINK Study.

Chronic kidney disease (CKD) studies have reported variable prevalence of brain pathologies, in part due to low inclusion of participants with moderate to severe CKD. To measure the association between kidney function biomarkers and brain MRI findings in CKD. In the BRINK (BRain IN Kidney Disease) study, MRI was used to measure gray matter volumes, cerebrovascular pathologies (white matter hyperintensity (WMH), infarctions, microhemorrhages), and microstructural changes using diffusion tensor imaging (DTI). We performed regression analyses with estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR) as primary predictors, and joint models that included both predictors, adjusted for vascular risk factors. We obtained 240 baseline MRI scans (150 CKD with eGFR <45 in ml/min/1.73 m2; 16 mild CKD: eGFR 45-59; 74 controls: eGFR≥60). Lower eGFR was associated with greater WMH burden, increased odds of cortical infarctions, and worsening diffusion changes throughout the brain. In eGFR models adjusted for UACR, only cortical infarction associations persisted. However, after adjusting for eGFR, higher UACR provided additional information related to temporal lobe atrophy, increased WMH, and whole brain microstructural changes as measured by increased DTI mean diffusivity. Biomarkers of kidney disease (eGFR and UACR) were associated with MRI brain changes, even after accounting for vascular risk factors. UACR adds unique additional information to eGFR regarding brain structural and diffusion biomarkers. There was agreater impact of kidney function biomarkers on cerebrovascular pathologies and microstructural brain changes, suggesting that cerebrovascular etiology may be the primary driver of cognitive impairment in CKD.

Cognitive Changes in Chronic Kidney Disease and After Transplantation.

Cognitive impairment is very common in chronic kidney disease (CKD) and is strongly associated with increased mortality. This review article will discuss the pathophysiology of cognitive impairment in CKD, as well as the effect of dialysis and transplantation on cognitive function. In CKD, uremic toxins, hyperparathyroidism and Klotho deficiency lead to chronic inflammation, endothelial dysfunction and vascular calcifications. This results in an increased burden of cerebrovascular disease in CKD patients, who consistently have more white matter hyperintensities, microbleeds, microinfarctions and cerebral atrophy on magnetic resonance imaging scans. Hemodialysis, although beneficial in terms of uremic toxin clearance, also contributes to cognitive decline by causing rapid fluid and osmotic shifts. Decreasing the dialysate temperature and increasing total dialysis time limits these shifts and helps maintain cognitive function in hemodialysis patients. For many patients, kidney transplantation is the preferred treatment modality, because it reverses the underlying mechanisms causing cognitive impairment in CKD. These positive effects have to be balanced against the possible neurotoxicity of infections and immunosuppressive medications, especially glucocorticosteroids and calcineurin inhibitors. A limited number of studies have addressed the overall effect of transplantation on cognitive function. These have mostly found an improvement after transplantation, but have a limited applicability to daily practice because they have only included relatively young patients.