Cognitive impairment is a frequent finding in patients with chronic kidney disease (CKD). We examined cognitive performance in a prospective study of 119 patients with CKD stages 3-5 (including dialysis) and 54 control patients of the same age without CKD but with similar vascular risk profiles. Analysis included a comprehensive test battery evaluating memory, information processing speed, executive function, language, and visuoconstructive function, in addition to depression and anxiety. Thirty percent of patients with CKD had cognitive deficits (one or more s.d. below control patient performance). Cognitive deficits (T-value related to published norm values) were mild but significantly decreased to 48.8 in patients with stage 3-5 CKD not requiring hemodialysis and 47.2 in patients with stage 5D disease requiring hemodialysis, compared with 51.5 in control patients. Linear regressions among patients with CKD (forced entry strategy) showed that age (β=-0.50 per s.d.), HbA1c (β=-0.18 per s.d.), and fibrinogen (β=-0.18 per s.d.) predicted cognitive performance. Interestingly, HbA1c discriminated cognition in all age groups, while fibrinogen differentiated cognition particularly in patients over 70 years of age. Thus, our cross-sectional study suggests the severity of cognitive impairment in CKD is mild. As such, longitudinal studies are required to further characterize the role of cognitive deficits in CKD.

BackgroundQuality of life (QoL) impairment is a well-known consequence of chronic kidney disease (CKD). The factors influencing QoL and late life functional health are poorly examined.MethodsUsing questionnaires combined with neuropsychological examinations, we prospectively evaluated physical, cognitive, and emotional factors influencing QoL, functional health and participation in community dwelling in 119 patients with CKD stages 3–5 including hemodialysis (61.5±15.7years; 63% men) and 54 control patients of the same age without CKD but with similar cardiovascular risk profile.ResultsCompared with control patients, CKD patients showed impairment of the physical component of QoL and overall function, assessed by the SF-36 and LLFDI, whereas disability, assessed by LLFDI, was selectively impaired in CKD patients on hemodialysis. Multivariable linear regressions (forced entry) confirmed earlier findings that CKD stage (β = −0.24; p = 0.012) and depression (β = −0.30; p = 0.009) predicted the QoL physical component. Hitherto unknown, CKD stage (β = −0.23; p = 0.007), cognition (β = 0.20; p = 0.018), and depression (β = −0.51; <0.001) predicted disability assessed by the LLFDI, while age (β = −0.20; p = 0.023), male gender (B = 5.01; p = 0.004), CKD stage (β = −0.23; p = 0.005), stroke history (B = −9.00; p = 0.034), and depression (β = −0.41; p<0.001) predicted overall function. Interestingly, functional health deficits, cognitive disturbances, depression, and anxiety were evident almost only in CKD patients with coronary heart disease (found in 34.2% of CKD patients). The physical component of QoL and functional health decreased with age and depressive symptoms, and increased with cognitive abilities.ConclusionsIn CKD, QoL, functional health, and participation in community dwelling are influenced by physical, cognitive, and emotional factors, most prominently in coronary heart disease patients.

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Disturbed brain-to-blood elimination of β-amyloid (Aβ) promotes cerebral Aβ accumulation in Alzheimer's disease. Considering that the kidneys are involved in Aβ elimination from the blood, we evaluated how chronic kidney disease (CKD) affects plasma Aβ. In 106 CKD patients stages 3-5 (including 19 patients on hemodialysis and 15 kidney recipients), 53 control subjects with comparable vascular risk profile and 10 kidney donors, plasma Aβ was determined using electrochemiluminescence immunoassay and gel electrophoresis followed by Western blotting. Plasma Aβ increased with CKD stage (control = 182.98 ± 76.73 pg/ml; CKD3A = 248.34 ± 103.77 pg/ml; CKD3B = 259.25 ± 97.74 pg/ml; CKD4 = 489.16 ± 154.16 pg/ml; CKD5 = 721.19 ± 291.69 pg/ml) and was not influenced by hemodialysis (CKD5D = 697.97 ± 265.91 pg/ml). Renal transplantation reduced plasma Aβ (332.57 ± 162.82 pg/ml), whereas kidney donation increased it (251.51 ± 34.34 pg/ml). Gel electrophoresis confirmed stage-dependent elevation namely of Aβ1-40, the most abundant Aβ peptide. In a multivariable regression including age, sex, estimated glomerular filtration rate (eGFR), potassium, hemoglobin, urine urea, and urine total protein, the factors eGFR (β = -0.42, p < 0.001), hemoglobin (β = -0.17, p = 0.020), and urine protein (β = 0.26, p = 0.008) were associated with plasma Aβ. In a regression including age, sex, eGFR, potassium, hemoglobin and the vascular risk factors systolic blood pressure, smoking, LDL, HDL, HbA1c, body mass index, brain-derived natriuretic peptide and fibrinogen, the factors eGFR (β = -0.53, p < 0.001), body mass index (β = -0.17, p = 0.022), and fibrinogen (β = 0.18, p = 0.024) were associated with plasma Aβ. Our results demonstrate a stage-dependent plasma Aβ increase that is augmented by loss of glomerulotubular integrity, low body weight, and inflammation, demonstrating a multifaceted role of renal dysfunction in Aβ retention.

Background: The thalamus plays an essential role in cognition. Cognitive deficits have to date mostly been studied retrospectively in chronic thalamic stroke in small cohorts. Studies prospectively evaluating the evolution of cognitive deficits and their association with thalamic stroke topography are lacking. This knowledge is relevant for targeted patient diagnostics and rehabilitation. Methods: Thirty-seven patients (57.5±17.5 [mean±SD] years, 57% men) with first-ever acute isolated ischemic stroke covering the anterior (n=5), paramedian (n=12), or inferolateral (n=20) thalamus and 37 in-patient controls without stroke with similar vascular risk factors matched for age and sex were prospectively studied. Cognition was evaluated using predefined tests at 1, 6, 12, and 24 months. Voxel-based lesion-symptom mapping was used to determine associations between neuropsychological deficits and stroke topography. Results: Patients with anterior thalamic stroke revealed severe deficits in verbal memory (median T score [Q1–Q3]: 39.1 [36.1–44.1]), language (31.8 [31.0–43.8]), and executive functions (43.8 [35.5–48.1]) at 1 month compared with controls (verbal memory: 48.5 [43.6–61.0], language: 55.7 [42.3–61.1], executive functions: 51.3 [50.1–56.8]). Patients with paramedian thalamic stroke showed moderate language (44.7 [42.8–55.9]) and executive (49.5 [44.3–55.1]) deficits and no verbal memory deficits (48.1 [42.5–54.7]) at 1 month compared with controls (59.0 [47.0–64.5]; 59.6 [51.1–61.3]; 52.5 [44.2–55.3]). The language and executive deficits in paramedian thalamic stroke patients almost completely recovered during follow-up. Intriguingly, significant deficits in verbal memory (44.7 [41.5–51.9]), language (47.5 [41.8–54.1]), and executive functions (48.2 [46.2–59.7]) were found in inferolateral thalamic stroke patients at 1 month compared with controls (50.5 [46.7–59.9]; 57.0 [51.2–62.9]; 57.4 [51.2–60.7]). Language, but not executive deficits persisted during follow-up. Voxel-based lesion-symptom mapping revealed an association of verbal memory deficits with anterior thalamus lesions and an association of non-verbal memory, language, and executive deficits with lesions at the anterior/paramedian/inferolateral border. Conclusions: All 3 stroke topographies exhibited significant deficits in diverse cognitive domains, which recovered to a different degree depending on the stroke localization. Our study emphasizes the need for comprehensive neuropsychological diagnostics to secure adequate patient rehabilitation.