Disentangling the Relationship Between Chronic Kidney Disease and Cognitive Disorders

Kelly, Dearbhla M.; Rothwell, Peter M.

doi:10.3389/fneur.2022.830064

Cited by 30 publications

(23 citation statements)

References 133 publications

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“…There are several theories linking poor kidney function to dementia, including the kidney-brain-axis theory that outlines the possible neuropathologic outcomes of poor kidney function . Increased dementia risk may be a result of the physiological consequences associated with constant blood flow in both the kidneys and the brain .…”

Section: Discussionmentioning

confidence: 99%

Association of Kidney Function With Development of Alzheimer Disease and Other Dementias and Dementia-Related Blood Biomarkers

et al. 2023

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ImportancePrevious research has suggested an association of kidney function with risk of Alzheimer disease (AD) or other dementias and dementia-related blood biomarkers, but a distinct association remains unclear.ObjectiveTo evaluate the association of kidney function with risk of diagnosis of incident AD or dementia within 17 years and with the blood biomarkers neurofilament light (NfL), phosphorylated tau181 (p-tau181), and glial fibrillary acidic protein (GFAP).Design, Setting, and ParticipantsIn this prospective, population-based cohort study and nested case-control study, 9940 participants in Germany were enrolled between 2000 and 2002 by their general practitioners and followed up for up to 17 years. Participants were included if information on dementia status and creatinine/cystatin C measurements were available. A subsample of participants additionally had measurements of NfL, p-tau181, and GFAP obtained from blood samples. Statistical analysis was performed from January 3 to November 25, 2022.ExposuresImpaired kidney function, based on estimated glomerular filtration rate less than 60 mL/min/1.73 m2 according to the 2021 Chronic Kidney Disease Epidemiology Collaboration creatinine–cystatin C equation.Main Outcomes and MeasuresAll-cause dementia, AD, and vascular dementia diagnosis, as well as log-transformed levels of NfL, p-tau181, and GFAP in blood.ResultsOf 6256 participants (3402 women [54.4%]; mean [SD] age at baseline, 61.7 [6.6] years), 510 received an all-cause dementia diagnosis within 17 years of baseline. The dementia-related blood biomarker nested case-control sample included 766 participants. After adjusting for age and sex, impaired kidney function at baseline was not associated with a higher risk of all-cause dementia (hazard ratio [HR], 0.95; 95% CI, 0.69-1.29), AD (HR, 0.94; 95% CI, 0.55-1.63), or vascular dementia diagnosis (HR, 1.06; 95% CI, 0.65-1.70) within 17 years. In the cross-sectional analysis, after adjusting for age and sex, impaired kidney function was significantly associated with NfL and p-tau181 levels in blood (NfL: β = 0.47 and P &lt; .001; p-tau181: β = 0.21 and P = .003). After adjusting for age and sex, significant associations with GFAP levels were evident only among men (men: β = 0.31 and P = .006; women: β = −0.12 and P = .11).Conclusions and RelevanceIn this population-based study of community-dwelling adults, reduced kidney function was associated with increased levels of dementia-related blood biomarkers but not increased dementia risk. Kidney function might influence the accuracy of dementia-related blood biomarkers and should be considered in clinical translation.

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Section: Discussionmentioning

confidence: 99%

Association of Kidney Function With Development of Alzheimer Disease and Other Dementias and Dementia-Related Blood Biomarkers

et al. 2023

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“…Podvin and others (2016) found that C2orf40 is a neuroimmune factor in Alzheimer’s disease. The SLC47A1 (solute carrier family 47 member 1) protein is expressed in both the kidney and the brain, and recent research has suggested a linkage between kidney diseases and Alzheimer’s disease (Shi and others , 2018; Kelly and Rothwell, 2022).…”

Section: Resultsmentioning

confidence: 99%

clrDV: A differential variability test for RNA-Seq data based on the skew-normal distribution

Khang

2022

Preprint

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Genes that show differential variability between conditions are important for complementing a systems biology understanding of the molecular players involved in a biological process. Under the dominant paradigm for modeling RNA-Seq gene counts using the negative binomial model, tests of differential variability are challenging to develop, owing to dependence of the variance on the mean. The limited availability of methods for detecting genes with differential variability means that researchers often omit differential variability as an analytical step in RNA-Seq data analysis. Here, we describe clrDV, a statistical method for detecting genes that show differential variability between two populations. clrDV is based on a compositional data analysis framework. We present the skew-normal distribution for modeling gene-wise null distribution of centered log-ratio transformation of compositional RNA-seq data. Simulation results show that clrDV has false discovery rate and Type II error that are on par with or superior to existing methodologies. In addition, its run time is faster than the closest competitor's, and remains relatively constant for increasing sample size per group. Analysis of a large neurodegenerative disease RNA-Seq dataset using clrDV recovers multiple gene candidates that have been reported to be associated with Alzheimer's disease. Additionally, we find that the majority of genes with differential variability have smaller relative gene expression variance in the Alzheimer's disease population compared to the control population.

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“…Moreover, the prevalence and degree of cognitive decline increase with advanced CKD stages. When CKD progresses from Stage 3 to Stage 5, the prevalence of cognitive impairment among patients increases from 20–50% to 70% [ 18 ]. Studies examining the relationship between CKD and cognitive function have focused largely on hemodialysis patients, and little is known about cognitive dysfunction in pre-dialysis Stage 3–4 CKD.…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Zhou

et al. 2023

Brain Sciences

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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.

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Disentangling the Relationship Between Chronic Kidney Disease and Cognitive Disorders

Cited by 30 publications

References 133 publications

Association of Kidney Function With Development of Alzheimer Disease and Other Dementias and Dementia-Related Blood Biomarkers

Association of Kidney Function With Development of Alzheimer Disease and Other Dementias and Dementia-Related Blood Biomarkers

clrDV: A differential variability test for RNA-Seq data based on the skew-normal distribution

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

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