Chronic kidney disease (CKD) is associated with an elevated risk of neurocognitive disorders (NCDs). It remains unclear whether CKD-related NCDs have a specific cognitive pattern or are earlier-onset phenotypes of the main NCDs (vascular NCDs and Alzheimer's disease). We used the Mini Mental State Examination score (MMSE) to assess cognitive patterns in 3003 CKD patients (stage 3–4) followed up over 5 years in the Chronic Kidney Disease–Renal Epidemiology and Information Network (CKD-REIN) cohort. After normalizing MMSE scores to a 0-to-100 scale, the associations between the baseline estimated glomerular filtration rate (eGFR, using the Chronic Kidney Disease Epidemiology Collaboration creatinine formula) and changes in each MMSE domain score were assessed in linear mixed models. Patients (age: 67 ± 13 years old; males: 65%, mean eGFR: 33± 12 mL/min/1.73 m²) had a good baseline cognitive functions: the mean MMSE score was 26.9/30 ± 2.9. After adjustment for age, sex, educational level, depression (past or present), cardiovascular risk factors and cerebrovascular disease, a lower baseline eGFR (per 10 mL/min/1.73 m²) was associated with a 0.53-point decrement [P < .001; 95% confidence interval (CI) (–0.98, –0.08)] for orientation, a 1.04-point decrement [P = .03; 95% CI (–1.96, –0.13)] for attention and calculation, a 0.78-point decrement [P = .003; 95% CI (–1.30, –0.27)] for language, and a 0.94-point decrement [P = .02; 95% CI (–1.75, –0.13)] for praxis. Baseline eGFR was not, however, associated with significant changes over time in MMSE domain scores. A lower eGFR in CKD patients was associated with early impairments in certain cognitive domains: praxis, language and attention domains before an obvious cognitive decline. Early detection of NCD in CKD patients must be performed before clinically cognitive decline using preferably tests assessing executive, attentional functions and language, rather than memory tests. This early cognitive screening could lead to a better management of cognitive impairment and their consequences on CKD management.

Depression is common in patients with chronic kidney disease (CKD). Experimental studies suggest the role of urea toxicity in depression. We assessed both the incidence of antidepressant prescriptions and depressive symptoms (measured by CESD (Center for Epidemiologic Depression) scale) in 2505 patients with CKD (Stage 3–4) followed up over 5 years in the Chronic Kidney Disease Renal Epidemiology and Information Network (CKD-REIN) cohort. We used a joint model to assess the association between the serum urea level and incident antidepressant prescriptions, and mixed models for the association between the baseline serum urea level and CESD score over the 5-year follow-up. Among the 2505 patients, 2331 were not taking antidepressants at baseline. Of the latter, 87 started taking one during a median follow-up of 4.6 years. After adjustment for confounding factors, the hazard ratio for incident antidepressant prescription associated with the serum urea level (1.28 [95%CI, 0.94,1.73] per 5 mmol/L increment) was not significant. After adjustment, the serum urea level was associated with the mean change in the CESD score (β = 0.26, [95%CI, 0.11,0.41] per 5 mmol/L increment). Depressive symptoms burden was associated with serum urea level unlike depression events. Further studies are needed to draw firm conclusions and better understand the mechanisms of depression in CKD.

Various epidemiological datasets and pathophysiological hypotheses have highlighted a significant link between chronic kidney disease (CKD) and cognitive impairment (CI); each condition can potentially exacerbate the other. Here, we review the mutual consequences of CKD and CI on health outcomes and care pathways and highlight the complexities due to the involvement of different specialists. Our narrative review covers (i) the burden of CI among patients with CKD, (ii) the impact of CI on kidney health, (iii) access to kidney replacement therapy for people with CI, (iv) resources in cognitive care and (v) potential models for integrated ‘nephro-cognitive’ care. CI (ranging from mild CI to dementia) has a significant impact on older adults, with a high prevalence and a strong association with CKD. Furthermore, CI complicates the management of CKD and leads to a higher mortality rate, poorer quality of life and higher healthcare costs. Due to difficulties in symptom description and poor adherence to medical guidelines, the presence of CI can delay the treatment of CKD. Access to care for patients with both CKD and CI is hindered by physical, cognitive and systemic barriers, resulting in less intensive, less timely care. Multidisciplinary approaches involving nephrologists, geriatricians, neurologists and other specialists are crucial. Integrated care models focused on person-centred approaches, shared decision-making and continuous co-management may improve outcomes. Future research should focus on the putative beneficial effects of these various strategies on both clinical and patient-reported outcomes.

Chronic kidney disease (CKD) leads to the accumulation of uremic toxins (UTs). Studies have suggested that UTs are associated with cognitive impairment (CI) in patients with CKD. Recently, studies reported that phenylacetylglutamine (PAG) contributes to the association between CKD and CI. However, this association has not been investigated in nondialysis-dependent adults with CKD. The CKD–Renal Epidemiology and Information Network (CKD-REIN) cohort study included 3033 patients with CKD stages 2 to 5. This cross-sectional analysis included those with a PAG measurement and a mini-mental state examination (MMSE) score within 3 months of each other. CI was defined as an MMSE score ≤ 26 out of 30. Logistic regression was used to assess the association between PAG and CI. Of the 2590 patients included (mean [SD] age: 67 [13] years, mean [SD] estimated glomerular filtration rate [eGFR]: 34 [13] ml/min per 1.73 m², median [interquartile range, IQR] PAG level: 2.1 [1.2–3.6] mg/l), 908 (35%) presented an MMSE score ≤ 26 out of 30. After adjustment for sociodemographic factors (age, male sex, and educational level), cardiovascular risk factors, cerebrovascular disease, current depression, eGFR, urinary albumin-to-creatinine ratio (uACR), and UTs known to be associated with CI risk, a 2-fold increase in the PAG level was associated with CI (odds ratio [OR] [95% confidence interval]: 1.12 [1.01–1.23]). This study shows that a higher serum PAG level was associated with CI in nondialysis-dependent adults with CKD and highlight a new UT associated with CI in patients with CKD. Further studies are needed to confirm the causal nature of the association and to explore strategies for reducing serum PAG levels to protect cognition.

Background: People with chronic kidney disease (CKD) have an elevated risk of cognitive impairment (CI). Medications with anticholinergic activity are recognized for their adverse reactions on central nervous system. The putative association between the anticholinergic burden and CI has not previously been evaluated in patients with CKD. The study aimed to (i) describe prescriptions of medications with anticholinergic activity, (ii) analyze factors associated with these prescriptions, and (iii) evaluate the anticholinergic burden's association with cognitive performance. Methods: CKD‐REIN, a prospective cohort study, enrolled nephrology outpatients with a confirmed diagnosis of CKD (eGFR <60 mL/min/1.73m ² ). Drug prescriptions were recorded prospectively during the 5‐year follow‐up. Mini Mental State Examination (MMSE) was assessed at baseline and CI was defined as an MMSE score <24/30. For each patient, the anticholinergic burden was determined by summing the Anticholinergic Cognitive Burden (ACB) scores of all prescription drugs at baseline. Multinomial logistic regression was used to analyze factors associated with the ACB score. Logistic regression was used to evaluate the association between the cognitive impairment and the anticholinergic burden at baseline. Results: At baseline, 3007 patients (median age [IQR], 69[60–76]; 65% men) had MMSE data and were included. 1549 (52%) of these patients were taking at least one drug with anticholinergic properties. Most (1092; 70%) had a low anticholinergic burden, 294 (19%) had a moderate anticholinergic burden, and 163 (11%) had a high anticholinergic burden. A history of neurological/psychiatric disorders and a higher number of daily drugs were associated with a greater probability of having a high anticholinergic burden (odds ratio (OR) [95% confidence interval (95% CI)] = 1.88[1.29;2.74] and 1.53[1.45;1.61], respectively). Patients with a high anticholinergic burden had a significantly higher probability of presenting cognitive impairment, compared with patients without an anticholinergic burden (OR[95% CI] = 1.76[1.12;2.75]) after adjustment for sociodemographic factors, comorbidities, laboratory data, and the number of medications taken daily. Conclusions: The results of our study emphasize the need for caution in the prescription of drugs with anticholinergic properties to patients with CKD.