Patients with chronic kidney disease (CKD) are at substantially higher risk for developing cognitive impairment compared with the general population, and both lower glomerular filtration rate and the presence of albuminuria are associated with the development of cognitive impairment and poorer cognitive function. Given the excess of vascular disease seen in individuals with CKD, cerebrovascular disease is likely the predominant pathology underlying these associations, though impaired clearance of uremic metabolites, depression, sleep disturbance, anemia, and polypharmacy may also contribute. Modification of vascular disease risk factors may be helpful in limiting decline, though definite data are lacking. Specific to CKD, targeting a low blood pressure and reduction in albuminuria with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may slow cognitive decline, albeit modestly. Initiation of dialysis can improve severe impairment associated with uremia but does not appear to affect more subtle chronic cognitive impairment. In contrast, kidney transplantation appears to lead to improved cognitive function in many transplant recipients, suggesting that dialysis methods do not provide the same cognitive benefits as having a functioning kidney. Management of patients with both CKD and cognitive impairment should include a comprehensive plan including more frequent follow-up visits; involvement of family in shared decision making; measures to improve compliance, such as written instruction and pill counts; and a focus on advance directives in conjunction with an emphasis on understanding an individual patient's life goals. Further research is needed on novel therapies, including innovative dialysis methods, that aim to limit the development of cognitive impairment, slow decline in those with prevalent impairment, and improve cognitive function.Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The purpose of this investigation was to examine the association between cognition disorders and microstructural white matter (WM) changes in maintenance hemodialysis end-stage renal disease (ESRD) patients.Twenty-six maintenance hemodialysis ESRD patients and 28 healthy controls underwent diffusion tensor imaging (DTI), Mini Mental State Examination (MMSE), Trial Marking Test-A&B (TMT-A&B), and white matter hyperintensity (WMH) assessment. Tract-based spatial statistics (TBSS) analyses was performed to evaluate WM changes in the patients. Relationships between behavioural performances, clinical data, and the DTI index were tested, respectively, by correlation analysis at the voxel level.ESRD patients showed significant decreased fractional anisotropy (FA) in 14 WM regions, and increased mean diffusivity (MD) and radial diffusivity (RD) in widespread regions. Significant positive correlations between FA values and MMSE scores were found in the right anterior corona radiata and the left anterior thalamic radiation; significant negative correlations between the TMT-B time consumption and FA values were identified in the bilateral superior longitudinal fasciculus. Positive linear relationships between MD, RD values, and the duration of hemodialysis were found in several WM regions.Structural damages to radiation and associative fibre tracts, caused by brain oedema and WM demyelination, may account for the cognitive deficits in ESRD patients.

MicroRNAs (miRNAs) are short noncoding RNA that participate in posttranscriptional gene regulation. However, little is understood about the roles of miRNAs in Alzheimer's disease (AD). In this study, we used next-generation sequencing on RNA extracted from the serum samples of 20 AD patients and 20 controls, yielding a total of 72 miRNAs with significantly changed expression levels. Among these candidates, we selected 9 miRNAs with most significant alteration in disease, and validated their expression levels using RT-qPCR analysis on serum samples from 45 AD patients and 40 control subjects. Thus, the serum levels of miR-146a-5p, 106b-3p, 195-5p, 20b-5p, and 497-5p were significantly higher, while those of miR-125b-3p, 29c-3p, 93-5p and 19b-3p were significantly lower in AD patients, compared with control subjects. Two miRNAs, miR-29c-3p and miR-19b-3p, were selected because both RNA deep-sequencing and q-PCR methods indicated lower serum levels of these miRNAs in AD patients. Computational analysis predicted that 3'-untranslated region of signal transduction and activator of transcription 3 (STAT3) mRNA is targeted both by miR-29c-3p and miR-19b-3p. Using SH-SY5Y human neuroblastoma cells, we showed that transfection with miR-29c-3p or miR-19b-3p inhibitor significantly increased STAT3 phosphorylation. Furthermore, Water maze test, which assesses the learning and memory deficits in rodents, showed that escape latency was significantly shorter in AD rats with overexpression of miR-29c-3p or miR-19b-3p than in control AD rats. These results suggest that miR-29c-3p or miR-19b-3p may contribute to the cognitive function. In conclusion, the serum levels of miR-29c-3p and miR-19b-3p are helpful biomarkers for AD.

(1) Background: Cognitive impairment (CI) is common in chronic kidney disease (CKD) and patients treated with hemodialysis. (2) Methods: The systematic review was prepared following the PRISMA statement (2013). The biomedical electronic databases MEDLINE and SCOPUS were searched. (3) Results: out of 1093 studies, only 30, which met problem and population criteria, were included in this review. The risk factors for CI can be divided into three groups: traditional risk factors (present in the general population), factors related to dialysis sessions, and nontraditional risk factors occurring more frequently in the HD group. (4) Conclusions: the methods of counteracting CI effective in the general population should also be effective in HD patients. However, there is a need to develop unique anti-CI approaches targeting specific HD risk factors, i.e., modified hemodialysis parameters stabilizing cerebral saturation and blood flow.

Associations between regional white matter lesion pathology and neuropsychological performance across the aging spectrum are not well understood and, to date, research has been largely contradictory and inconclusive. The current study set out to clarify some of the inconsistencies in the literature by relating volumetric analyses of white matter lesions (deep white matter lesions and periventricular lesions) to neuropsychological performance in a large clinical sample of older adults diagnosed with mild cognitive impairment.Seventy older adults with mild cognitive impairment were administered a comprehensive neuropsychological battery. White matter lesions identified on T2-weighted FLAIR images were quantified using a semi-automated volumetric approach (pixel thresholding).Results showed that, in contrast to performance on memory and naming tasks, total white matter lesions strongly predicted executive impairments, slowed processing speed, and visuospatial/construction difficulties. In addition, separate regression analyses demonstrated that results were primarily accounted for by deep white matter lesions (but not periventricular lesions), most likely due to frontal-subcortical circuitry disruption. Moreover, deep white matter lesions, but not periventricular lesions, significantly predicted overall poorer neuropsychological functioning after controlling for age, education, and level of depression.Taken together, findings demonstrate a differential influence of lesion type on cognitive impairment in mild cognitive impairment and implicate deep white matter lesions as being most detrimental in terms of neuropsychological functioning. Clinical, theoretical, and methodological implications of these results are discussed.

Up till now, the study of regional gray matter atrophy in Alzheimer's disease (AD) has been assessed with regions of interest, but this method is time-consuming, observer dependent, and poorly reproducible (especially in terms of cortical regions boundaries) and in addition is not suited to provide a comprehensive assessment of the brain. In this study, we have mapped gray matter density by means of voxel-based morphometry on T1-weighted MRI volume sets in 19 patients with mild AD and 16 healthy subjects of similar age and gender ratio and report highly significant clusters of gray matter loss with almost symmetrical distribution, affecting mainly and in decreasing order of significance the medial temporal structures, the posterior cingulate gyrus and adjacent precuneus, and the temporoparietal association and perisylvian neocortex, with only little atrophy in the frontal lobe. The findings are discussed in light of previous studies of gray matter atrophy in AD based either on postmortem or neuroimaging data and in relation to PET studies of resting glucose consumption. The limitations of the method are also discussed in some detail, especially with respect to the segmentation and spatial normalization procedures as they apply to pathological brains. Some potential applications of voxel-based morphometry in the study of AD are also mentioned.Copyright 2001 Academic Press.

Cognitive impairment commonly occurs in hemodialysis patients, with vascular disease potentially implicated in its pathogenesis. However, the relationship of detailed vascular assessment with cognitive function in patients new to hemodialysis has not been demonstrated.In a prospective study of incident hemodialysis participants enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in ESRD (PACE) study, we determined aortic stiffness by pulse-wave velocity (PWV), systemic arterial stiffness by the augmentation index (AIx) and central pulse pressure (cPP), and examined their associations with cognitive processing speed, executive function, and global cognitive impairment measured by the Trail making test A (TMTA), Trail making test B (TMTB), and the modified Mini-Mental State Exam (3MS).Mean baseline age was 55 ± 13 years, 58% were male, 72% were African American, 35% had coronary artery disease, 55% had diabetes, and 10% had cognitive impairment. At baseline, higher PWV and cPP were associated with a longer TMTA, and a higher PWV was associated with a longer TMTB, but the associations were attenuated after multivariable adjustment. At 1 year, PWV was not independently associated with TMTA, TMTB, or 3MS. However, unadjusted and adjusted analyses revealed every 10% increase in AIx and 10 mm Hg increase in cPP were associated with longer TMTB (time difference: 0.14; 95% confidence interval [CI]: 0.02-0.25 log-seconds; time difference: 0.11; 95% CI: 0.05-0.17 log-seconds) and global cognitive impairment (odds ratio [OR]: 10.23; 95% CI: 1.77-59.00; OR: 2.88; 95% CI: 1.48-5.59).Higher AIx and cPP, which are indicative of abnormal wave reflections in distal vessels, are associated with, and might contribute to, declining cognitive function in patients starting hemodialysis.

Cognitive impairment (CI) associated with chronic kidney disease (CKD) has received attention as an important problem in recent years. Causes of CI with CKD are multifactorial, and include cerebrovascular disease, renal anemia, secondary hyperparathyroidism, dialysis disequilibrium, and uremic toxins (UTs). Among these causes, little is known about the role of UTs. We therefore selected 21 uremic compounds, and summarized reports of cerebro-renal interactions associated with UTs. Among the compounds, uric acid, indoxyl sulfate, p-cresyl sulfate, interleukin 1-β, interleukin 6, TNF-α, and PTH were most likely to affect the cerebro-renal interaction dysfunction; however, sufficient data have not been obtained for other UTs. Notably, most of the data were not obtained under uremic conditions; therefore, the impact and mechanism of each UT on cognition and central nervous system in uremic state remains unknown. At present, impacts and mechanisms of UT effects on cognition are poorly understood. Clarifying the mechanisms and establishing novel therapeutic strategies for cerebro-renal interaction dysfunction is expected to be subject of future research. Copyright © 2014 Elsevier Inc. All rights reserved.

Cognitive impairment (CI) is highly prevalent among hemodialysis (HD) patients and is associated with increased morbidity and mortality. The aim was to compare cognitive function in HD patients with no history of stroke or dementia and well-matched controls. Studies are required to determine the impact of HD and chronic kidney disease-specific risks on CI.76 outpatients (50 receiving outpatient HD and 26 with normal kidney function matched for age and comorbidity) underwent a cross-sectional observational study. HD patients were well dialyzed and had optimal hemoglobin levels. A battery of eight neuropsychological tests was used. Outcomes included assessment scores of neurocognitive testing and prevalence and subtype of CI.Compared to controls, HD subjects had significantly lower composite scores for each tested cognitive domain. In each domain except memory, the percentage of subjects with impairment was significantly higher in HD subjects than controls. Differences between the groups were independent of vascular and dementia risk factors. 82% of HD subjects met criteria for CI versus 50% of controls. Non-amnestic subtype of CI was more prevalent in both groups.Well-dialyzed HD patients with optimized hemoglobin levels and with no history of stroke or dementia performed significantly worse on multiple measures of cognition compared to controls. A higher prevalence of non-memory impairment may suggest an underlying vascular versus neurodegenerative mechanism. HD and chronic kidney disease-specific risk factors may contribute to early CI not readily detected by routine screening methods.Copyright © 2011 S. Karger AG, Basel.

Cognitive impairment is common in hemodialysis patients and is associated with significant morbidity. Limited information exists about whether cognitive impairment is associated with survival and whether the type of cognitive impairment is important.Longitudinal cohort.Cognitive function was assessed at baseline and yearly using a comprehensive battery of cognitive tests in 292 prevalent hemodialysis patients.Using principal component analysis, individual test results were reduced into 2 domain scores, representing memory and executive function. By definition, each score carried a mean of 0 and SD of 1.Association of each score with all-cause mortality was assessed using Cox proportional hazards models adjusted for demographics and dialysis and cardiovascular (CV) risk factors.Mean age of participants was 63 years, 53% were men, 23% were African American, and 90% had at least a high school education. During a median follow-up of 2.1 (IQR, 1.1-3.7) years, 145 deaths occurred. Each 1-SD better executive function score was associated with a 35% lower hazard of mortality (HR, 0.65; 95% CI, 0.55-0.76). In models adjusting for demographics and dialysis-related factors, this relationship was partially attenuated but remained significant (HR, 0.81; 95% CI, 0.67-0.98), whereas adjustment for CV disease and heart failure resulted in further attenuation (HR, 0.87; 95% CI, 0.72-1.06). Use of time-dependent models showed a similar unadjusted association (HR, 0.62; 95% CI, 0.54-0.72), with the relationship remaining significant after adjustment for demographics and dialysis and CV risk factors (HR, 0.79; 95% CI, 0.66-0.94). Better memory was associated with lower mortality in univariate analysis (HR per 1 SD, 0.82; 95% CI, 0.69-0.96), but not when adjusting for demographics (HR, 1.00; 95% CI, 0.83-1.19).Patients with dementia were excluded from the full battery, perhaps underestimating the strength of the association.Worse executive function and memory are associated with increased risk of mortality. For memory, this association is explained by patient demographics, whereas for executive function, this relationship may be explained in part by CV disease burden.Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Fewer studies have focused on the independent association between mean corpuscular volume (MCV) and cognitive performance. This study was designed to characterize the cross-sectional association between MCV and cognitive performance in a large sample of Chinese residents (age≥45 years) from the China Health and Retirement Longitudinal Study (CHARLS). A total of 4023 male and 4173 female adults with MCV ≥ 80 fl were included for analysis. By multivariable linear regression analysis, for the total subjects, MCV level was significantly negatively associated with global cognitive function and episodic memory. When adjusted by sex, only in male subjects, higher MCV level was associated with reduced scores for global cognitive function, episodic memory and mental status. Via binary logistic regression analysis, the higher MCV level (MCV>100 fl) was associated with poor global cognitive function (OR = 1.601; 95% CI = 1.198–2.139; p = 0.001), episodic memory (OR = 1.679; 95% CI = 1.281–2.201; p<0.001), and mental status (OR = 1.422; 95% CI = 1.032–1.959; p = 0.031) for the whole participants. When testing this association by sex, the significant relationship between higher MCV level with worse episodic memory was observed both in male (OR = 1.690; 95% CI = 1.211–2.358; p = 0.002) and female (OR = 1.729; 95% CI = 1.079–2.770; p = 0.023) subjects; while the association between higher MCV level and poor global cognitive function (OR = 1.885; 95% CI = 1.329, 2.675; p<0.001) and mental status (OR = 1.544; 95% CI = 1.034, 2.306; p = 0.034) only existed in male subjects. Further studies are warranted to clarify the association between MCV level and cognitive performance by considering sex into consideration both cross-sectionally and longitudinally.

目的 了解维持性血液透析(maintenance hemodialysis,MHD)患者脂代谢紊乱的患病率和特点,并探讨其危险因素。方法 对北京朝阳医院血液净化中心205例MHD患者进行横断面研究;收集其临床资料和血脂指标。结果 1 205例MHD患者中有145例(70.7％)存在脂质代谢异常,主要表现为高密度脂蛋白胆固醇(HDL-C)降低、低密度脂蛋白胆固醇(LDL-C)增高和三酰甘油(TG)增高,患病率分别为53.2％、28.3％和26.8％。2 以45岁为界,将患者分为青年组(51例)和中老年组(154例)。青年组脂代谢异常患病率(36/51,70.6％)与中老年组(109/154,70.8%)相比差异无统计学意义。3 脂代谢异常者透析龄、性别和移植肾衰竭的比例明显高于无脂代谢异常者;而2组在年龄、血白蛋白、脂蛋白a、原发病方面差异无统计学意义。Logistic回归分析显示,男性、透析龄和移植肾衰竭是MHD患者并发脂代谢紊乱的独立危险因素。结论 MHD患者脂代谢紊乱的患病率高,主要表现为HDL-C降低、LDL-C增高和TG增高。青年透析患者脂蛋白紊乱的患病率与中老年透析患者相似。男性、透析龄和移植肾衰竭是MHD患者并发脂代谢紊乱的独立危险因素。

This hospital-based cross-sectional comparative observational study was performed to determine the pattern of lipid profile in patients on maintenance hemodialysis. The study was performed at the Department of Nephro-Urology, Liaquat University Hospital, Hyderabad, Pakistan from April 2008 to June 2008. Fifty patients with end-stage renal disease on maintenance hemodialysis (MHD) were studied. They comprised of 31 males and 19 females, the mean duration on HD was 7.58 +/- 2.05 yrs, with frequency of two to three sessions per week and each session lasting for four hours. Additionally, 25 healthy volunteers (16 male, 9 female) were also studied. After obtaining informed, written consent, general information of each patient was recorded on the proforma. After 12-hours fasting, blood samples were drawn from the arterio-venous fistula before starting dialysis. The total cholesterol, triglyceride (TG) or low density lipoprotein (LDL) levels more than 95th percentile for age and gender or high density lipoprotein (HDL) less then 35 mg/dL was defined as dyslipidemia. Descriptive and inferential statistical analysis were performed using SPSS version 16.0. The age among MHD and control groups was 47.88 +/- 13.92 and 54.56 +/- 11.16 years respectively. Serum TG and lipoprotein-a (LPa) were significantly increased (P = < 0.001 for each) while HDL-c was significantly lower (P = < 0.001) in MHD patients than in the control group. The serum cholesterol, LDL-c, VLDL-c and chylomicron levels were not significantly different in the two groups. Our study suggests that patients on MHD show abnormalities of lipid metabolism like hypertriglyceridemia, elevated lipoprotein-a and low HDL-c, which could contribute to atherosclerosis and cardiovascular disease that may increase the morbidity and mortality in these patients.

Dyslipoproteinemia and oxidative modification of low-density lipoprotein (oxLDL) contribute to the development of oxidative stress and atherosclerosis in chronic kidney disease (CKD). On the contrary, high-density lipoprotein cholesterol (HDL-C), especially HDL3-C subtype, has protective effect against oxidative damage. There is limited evidence referring HDL-C subclass levels in patients on dialysis. This study was designed to compare lipid abnormalities and oxLDL levels in hemodialysis (HD) and peritoneal dialysis (PD) patients. Serum lipids, HDL subclasses, and oxLDL were measured in 55 patients with CKD-stage 5 (31 patients on HD and 24 patients on PD) and in 21 normal controls (NC). The results showed that in dialysis patients, triglycerides were higher than in controls (p < 0.0001) and HDL-C was significantly lower (p < 0.0001). The HDL2-C subclass concentration did not differ significantly between patients and controls, while HDL3-C was lower in patients (11 ± 0.5 mg/dL) than in NC (23 ± 1, p < 0.0001). oxLDL levels were markedly increased in patients (1.92 ± 0.29 mg/L) compared to NC (0.22 ± 0.05, p < 0.0001). Patients on PD had higher levels of cholesterol (p < 0.001) and apolipoprotein B (p < 0.05) than patients on HD. However, HDL-C, HDL-C subclasses, and oxLDL concentrations did not differ significantly between PD and HD patients. It is concluded that patients with CKD have a nearly 10-fold elevation of oxLDL compared with NC. Patients on PD have differences in the lipid profile compared with patients on HD; however, both modalities seem to possess similar potential to atherosclerosis development.

The importance of neuroglia in maintaining normal brain function under physiological and pathological conditions has been supported by growing evidence in recent years. The most important issues regarding glial metabolism and function include the cooperation between glial populations and neurons, morphological and functional changes in pathological states, and the role in the onset and progression of neurodegenerative diseases. Although lipid accumulation and further lipid droplet production in neurodegenerative disease brain models have been observed for a long time, the dynamic development of brain lipid droplet research in recent years suggests its role in the development and progression of neurodegenerative diseases was previously underestimated. First recognized as organelles of lipid storage, lipid droplets (LDs) have emerged as an important organelle in metabolic diseases, inflammation, and host defense. Dynamic changes in lipid metabolism within neurons and glial cells resulting in lipid accumulation and lipid droplet formation are present in brain models of various neurodegenerative diseases, yet their role in the brain remains largely unexplored. This paper first reviews the metabolism and accumulation of several major lipids in the brain and discusses the regulation of lipid accumulation in different types of brain cells. We explore the potential role of intracellular lipid accumulation in the pathogenesis of neurodegeneration, starting from lipid metabolism and LDs biogenesis in glial cells, and discuss several pathological factors that promote lipid droplet formation, mainly focusing on oxidative stress, energy metabolism and glial cell-neuron coupling, which are closely related to the etiology and progression of neurodegenerative diseases. Finally, the directions and challenges of intracellular lipid metabolism in glial cells in neurodegeneration are discussed.© 2022. The Author(s).

We evaluate the association between high-density lipoprotein cholesterol (HDL-C) levels and physical and cognitive performance indicators in 85-year-old subjects.Prospective cohort study.A community-based study.321 subjects enrolled in the Octabaix Study.Functional status was determined using the Lawton-Brody Index (LI) and the Barthel Index (BI). Cognition was assessed using the modified Spanish version of the Mini-Mental State Examination (MEC). We also measured risks related to nutrition and falls, as well as comorbidity and chronic drug prescription. HDL-C serum concentrations <40 mg/dl for men and <46 mg/dl for women were used as cut-off values to discriminate between normal and low HDL-C concentrations.The sample consisted of 197 women (61%) and 124 men. Mean HDL-C levels were 56.5 ± 15 mg/dl, with gender differences being found (59.3 ± 15 mg/dl in women vs. 52.1 ± 13 mg/dl in men; p<0.0001). Sixty-one subjects (19%) had low HDL-C values. HDL-C levels correlated with BI (r=0.11, p=0.04) and LI (r=0.17, p=0.002) scores, but not with MEC scores (r=0.08, p=0.13). Poor BI and LI scores, lower MEC scores, a risk of falls and malnutrition, and polypharmacy were all associated with lower HDL-C values in the bivariate analysis. Multiple logistic regression analysis showed only a significant association between normal HDL-C serum values and better BI scores (p<0.001, OR 1.02, 95% CI 1.01-1.04).Individuals with higher levels of HDL-C had better functional and cognitive status, but after multivariate analysis this relationship only remained significant for functional status.