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Zoccali C, Mallamaci F, Wagner CA, Unwin R, Nedergaard M, Hafez G, Malyszko J, Pepin M, Massy Z, Paolisso G, Remuzzi G, Capasso GB. Genetic and circulating biomarkers of cognitive dysfunction and dementia in CKD. Nephrol Dial Transplant 2025; 40:ii64-ii75. [PMID: 40080085 PMCID: PMC11905751 DOI: 10.1093/ndt/gfae259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Indexed: 03/15/2025] Open
Abstract
Chronic kidney disease (CKD) is commonly accompanied by cognitive dysfunction and dementia, which, in turn, increase the risk of hospitalization, cardiovascular events and death. Over the last 30 years, only four studies focused on genetic markers of cognitive impairment in CKD and kidney failure (KF), indicating a significant gap in research. These studies suggest potential genetic predispositions to cognitive decline in CKD patients but also underscore the necessity for more comprehensive studies. Seventeen reports have established connections between cognitive function and kidney disease markers such as estimated glomerular filtration rate (eGFR), Cystatin C and albuminuria. A rapid eGFR decline has been associated with cognitive deterioration and vascular dementia, and mild to moderate eGFR reductions with diminished executive function in elderly men. Various biomarkers have been associated to Alzheimer's disease or dementia in CKD and KF. These include amyloid beta and phosphorylated tau proteins, uremic toxins, gut microbiota, metabolic indicators, hypertension, endothelial dysfunction, vitamins and inflammation. However, the causal relevance of these associations remains unclear. Overall, the available evidence points to a complex interplay between the different biomarkers and cognitive health in CKD patients, underscoring the need for more research to elucidate these relationships.
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Affiliation(s)
- Carmine Zoccali
- Renal Research Institute, NY, USA
- Institute of Molecular Biology and Genetics (Biogem), Ariano Irpino, Italy
- Associazione Ipertensione Nefrologia Trapianto Renale (IPNET), c/o Nefrologia, Grande Ospedale Metropolitano, Reggio Calabria, Italy
| | - Francesca Mallamaci
- Nephrology, Dialysis and Transplantation Unit, Grande Ospedale Metropolitano
- CNR-IFC, Institute of Clinical Physiology, Research Unit of Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension of Reggio Calabria, Italy
| | - Carsten A Wagner
- Institute of Physiology, University of Zurich, Zurich, Switzerland
| | - Robert Unwin
- UCL Department of Renal Medicine, Royal Free Hospital, London, UK
| | - Maiken Nedergaard
- Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY, USA
- Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Gaye Hafez
- Department of Pharmacology, Faculty of Pharmacy, Altinbas University, Istanbul, Turkey
| | - Jolanta Malyszko
- Department of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Marion Pepin
- Department of Nephrology, Ambroise Paré University Medical Center, APHP, Paris, France
- Department of Geriatrics, Ambroise Paré University Medical Center, APHP, Boulogne-Billancourt, France
| | - Ziad Massy
- Paris-Saclay University, UVSQ, Inserm, Clinical Epidemiology Team, Centre de Recherche en Epidémiologie et Santé des Populations (CESP), Villejuif, France
- Association pour l'Utilisation du Rein Artificiel (AURA), Paris and Department of Nephrology, Ambroise Paré University Medical Center, APHP, Paris, France
| | - Giuseppe Paolisso
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy
- UniCamillus, International Medical University, Rome, Italy
| | - Giuseppe Remuzzi
- Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo and Milan, Italy
| | - Giovambattista B Capasso
- Institute of Molecular Biology and Genetics (Biogem), Ariano Irpino, Italy
- Department of Translational Medical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
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An X, Cui Y, Qin M, Zhou J, Liu Q, Ye H. The mediating role of nutritional indicators in the association between estimated glomerular filtration rate and cognitive impairment in older adults. Psychogeriatrics 2024; 24:1187-1197. [PMID: 39149813 DOI: 10.1111/psyg.13176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 07/09/2024] [Accepted: 07/28/2024] [Indexed: 08/17/2024]
Abstract
BACKGROUND Cognitive impairment (CI) is common in older adults, especially those with renal dysfunction. We aimed to investigate the complex relationships among renal function, nutritional status, and CI in older people free from late chronic kidney disease (CKD) and severe CI. METHODS A study of older people (≥60 years old) with an estimated glomerular filtration rate (eGFR) of >30 mL/min/1.73 m2 and Montreal Cognitive Assessment (MoCA) scores of >10 (n = 237) was conducted at Beijing Tongren Hospital. Their eGFR was determined using the CKD-EPI-cr-Cysc equation. Cognitive function was evaluated with the MoCA. We tested the relationship between eGFR and MoCA scores using Spearman correlation analysis and multivariate logistic regression analysis. We then conducted a mediation analysis to figure out the mediating roles of nutritional indicators (Mini Nutritional Assessment-Short Form (MNA-SF) scores, albumin (ALB), and haemoglobin (HGB)) between the eGFR and MoCA scores. RESULTS The incidence of CI was 48.5% (115/237) in older people. Spearman correlation analysis revealed that the better the kidney function, the better the cognitive function (R = 0.297, P < 0.001). Multivariate logistic regression analysis revealed that eGFR decrease per 15 mL/min/1.73 m2 (OR: 1.415, 95% confidence interval: 1.055-1.896, P = 0.020) was related to CI after adjusting for age and sex. However, the eGFR was not associated with cognitive decline after adjusting for nutritional indicators, behavioural risk factors, other biomarkers, and chronic conditions, suggesting that eGFR is not independently associated with CI. Mediation analysis revealed that the MNA-SF scores (a*b = 0.006 (0.0002-0.012)) and HGB (a*b = 0.008 (0.001-0.017)) were mediating factors between the eGFR and MoCA scores. CONCLUSIONS A decline in renal function can directly lead to CI and can also exacerbate cognitive deficits through intermediary factors such as MNA-SF scores and HGB. Therefore, correcting anaemia and improving nutritional status are significantly important for enhancing cognitive function in older patients, especially those with renal dysfunction.
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Affiliation(s)
- Xiuping An
- Department of Geriatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Yao Cui
- Department of Geriatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Mingzhao Qin
- Department of Geriatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Jian Zhou
- Department of Geriatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Qian Liu
- Department of Geriatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Hui Ye
- Department of Geriatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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Yan Q, Liu M, Xie Y, Lin Y, Fu P, Pu Y, Wang B. Kidney-brain axis in the pathogenesis of cognitive impairment. Neurobiol Dis 2024; 200:106626. [PMID: 39122123 DOI: 10.1016/j.nbd.2024.106626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 07/31/2024] [Accepted: 08/02/2024] [Indexed: 08/12/2024] Open
Abstract
The kidney-brain axis is a bidirectional communication network connecting the kidneys and the brain, potentially affected by inflammation, uremic toxin, vascular injury, neuronal degeneration, and so on, leading to a range of diseases. Numerous studies emphasize the disruptions of the kidney-brain axis may contribute to the high morbidity of neurological disorders, such as cognitive impairment (CI) in the natural course of chronic kidney disease (CKD). Although the pathophysiology of the kidney-brain axis has not been fully elucidated, epidemiological data indicate that patients at all stages of CKD have a higher risk of developing CI compared with the general population. In contrast to other reviews, we mentioned some commonly used medicines in CKD that may play a pivotal role in the pathogenesis of CI. Revealing the pathophysiology interactions between kidney damage and brain function can reduce the potential risk of future CI. This review will deeply explore the characteristics, indicators, and potential pathophysiological mechanisms of CKD-related CI. It will provide a theoretical basis for identifying CI that progresses during CKD and ultimately prevents and treats CKD-related CI.
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Affiliation(s)
- Qianqian Yan
- Department of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Mengyuan Liu
- Department of Anesthesiology, Air Force Hospital of Western Theater Command, PLA, Chengdu 610011, China
| | - Yiling Xie
- Department of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Yimi Lin
- Department of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Ping Fu
- Department of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Yaoyu Pu
- Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China.
| | - Bo Wang
- Department of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, Chengdu 610041, China.
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Levassort H, Boucquemont J, Alencar de Pinho N, Lambert O, Helmer C, Metzger M, Teillet L, Frimat L, Combe C, Fouque D, Laville M, Jacquelinet C, Liabeuf S, Stengel B, Massy ZA, Pépin M. A new approach for cognitive impairment pattern in chronic kidney disease. Nephrol Dial Transplant 2024; 39:848-859. [PMID: 37950574 PMCID: PMC11181866 DOI: 10.1093/ndt/gfad244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Indexed: 11/12/2023] Open
Abstract
BACKGROUND 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). METHODS 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. RESULTS 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. CONCLUSION 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.
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Affiliation(s)
- Hélène Levassort
- Center for Research in Epidemiology and Population Health (CESP), Clinical Epidemiology Team, Paris-Saclay University, Versailles Saint-Quentin-en-Yvelines University, Inserm, Villejuif, France
- Department of Geriatric Medicine, Ambroise Paré Hospital, Boulogne-Billancourt, France
- Department of Nephrology, Ambroise Paré Hospital, Boulogne-Billancourt, France
| | - Julie Boucquemont
- Center for Research in Epidemiology and Population Health (CESP), Clinical Epidemiology Team, Paris-Saclay University, Versailles Saint-Quentin-en-Yvelines University, Inserm, Villejuif, France
| | - Natalia Alencar de Pinho
- Center for Research in Epidemiology and Population Health (CESP), Clinical Epidemiology Team, Paris-Saclay University, Versailles Saint-Quentin-en-Yvelines University, Inserm, Villejuif, France
| | - Oriane Lambert
- Center for Research in Epidemiology and Population Health (CESP), Clinical Epidemiology Team, Paris-Saclay University, Versailles Saint-Quentin-en-Yvelines University, Inserm, Villejuif, France
| | - Catherine Helmer
- University of Bordeaux, INSERM, Bordeaux Population Health Research Center, Bordeaux, France
| | - Marie Metzger
- Department of Geriatric Medicine, Ambroise Paré Hospital, Boulogne-Billancourt, France
| | - Laurent Teillet
- Center for Research in Epidemiology and Population Health (CESP), Clinical Epidemiology Team, Paris-Saclay University, Versailles Saint-Quentin-en-Yvelines University, Inserm, Villejuif, France
- Department of Geriatric Medicine, Ambroise Paré Hospital, Boulogne-Billancourt, France
| | - Luc Frimat
- Department of Nephrology, CHRU-Nancy, Lorraine University, Vandoeuvre, France
- EA 4360, INSERM CIC-EC CIE6, Medicine Faculty, Lorraine University, Apemac, France
| | - Christian Combe
- Department of Nephrology, Bordeaux University Hospital, INSERM, Univ. Bordeaux, Bordeaux, France
| | - Denis Fouque
- Department of Nephrology, LyonSud hospital – Hospices Civils de Lyon, Claude Bernard Lyon1 University, Pierre Benite, France
| | - Maurice Laville
- Carmen INSERM U1060, Claude Bernard Lyon 1 University, Pierre-Bénite, France
| | - Christian Jacquelinet
- Center for Research in Epidemiology and Population Health (CESP), Clinical Epidemiology Team, Paris-Saclay University, Versailles Saint-Quentin-en-Yvelines University, Inserm, Villejuif, France
- Medical and Scientific Department, Agence de la biomédecine, Saint-Denis la Plaine, France
| | - Sophie Liabeuf
- Pharmacology Department, Amiens University Medical Center, Amiens, France
- MP3CV Laboratory, EA7517, University of Picardie Jules Verne, Amiens, France
| | - Bénédicte Stengel
- Center for Research in Epidemiology and Population Health (CESP), Clinical Epidemiology Team, Paris-Saclay University, Versailles Saint-Quentin-en-Yvelines University, Inserm, Villejuif, France
| | - Ziad A Massy
- Center for Research in Epidemiology and Population Health (CESP), Clinical Epidemiology Team, Paris-Saclay University, Versailles Saint-Quentin-en-Yvelines University, Inserm, Villejuif, France
- Department of Nephrology, Ambroise Paré Hospital, Boulogne-Billancourt, France
| | - Marion Pépin
- Center for Research in Epidemiology and Population Health (CESP), Clinical Epidemiology Team, Paris-Saclay University, Versailles Saint-Quentin-en-Yvelines University, Inserm, Villejuif, France
- Department of Geriatric Medicine, Ambroise Paré Hospital, Boulogne-Billancourt, France
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Huang Y, Zhang R, Hong X, Liu S, Zhang S, Guo M, Shi L, Li Z, Liu Y. Correlation between sarcopenia index and cognitive function in older adult women: A cross-sectional study using NHANES data. J Clin Neurosci 2024; 122:73-79. [PMID: 38489954 DOI: 10.1016/j.jocn.2024.02.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Revised: 02/06/2024] [Accepted: 02/27/2024] [Indexed: 03/17/2024]
Abstract
OBJECTIVES The Sarcopenia Index (SI) has the potential as a biomarker for sarcopenia, which is characterized by muscle loss. There is a clear association between sarcopenia and cognitive impairment. However, the relationship between SI and cognitive impairment is yet to be fully understood. METHODS We employed data extracted from the U.S. National Health and Nutrition Examination Survey (NHANES) spanning the years 1999 to 2002. Our study encompassed individuals aged 65 to 80 who possessed accessible information regarding both SI and cognitive evaluations with a GFR ≥ 90. Cognitive function was assessed using the digit symbol substitution test (DSST). SI was calculated by serum creatinine (mg/dL)/cystatin C (mg/L)*100. Employing multivariate modeling, we estimated the connection between SI and cognitive performance. Furthermore, to enhance the reliability of our data analysis, we categorized SI using tertiles and subsequently calculated the P-value for trend. RESULTS After adjustment for potential confounders, we found SI was significantly and positively correlated with cognitive function scores both in older female in the American population [β = 0.160, 95 % confidence interval (CI) 0.050 to 0.271, P = 0.00461]. Similarly, when the total cognitive function score was treated as a categorical variable according to tertiles, higher SI was related to better total cognitive function scores in females [odds ratio (OR) = 3.968, 95 % CI 1.863 to 6.073, P = 0.00025] following adjustment for confounders. CONCLUSIONS Higher SI was correlated with a lower prevalence of cognitive impairment among older adult women with normal kidney function.
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Affiliation(s)
- Yajuan Huang
- Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Rui Zhang
- Department of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xinyang Hong
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Department of Neurology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shunjie Liu
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Department of Neurology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Su Zhang
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Department of Neurology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Mengxia Guo
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Department of Neurology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Lishuo Shi
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Center for Clinical Research, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhong Li
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Department of Neurology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Shenzhen Research Institute of Sun Yat-Sen University, Hi-tech Industrial Park, Nanshan District, Shenzhen, China; Guangdong Provincal Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
| | - Yunyun Liu
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Department of Neurology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
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Xiao Y, Devakumar V, Xu L, Liu L, Mo H, Hong X. Elevated serum creatinine levels and risk of cognitive impairment in older adults with diabetes: a NHANES study from 2011-2014. Front Endocrinol (Lausanne) 2023; 14:1149084. [PMID: 37900140 PMCID: PMC10603184 DOI: 10.3389/fendo.2023.1149084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 04/17/2023] [Indexed: 10/31/2023] Open
Abstract
Background The brain and kidney have similar microvascular structure, which makes them susceptible to certain common pathophysiological processes. In this study, we examined several indicators of kidney injury/function associated with cognitive function in older diabetic patients in the hope of finding effective markers for detecting cognitive impairment (CI). Methods A total of 2209 older participants (aged ≥60 years) from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) were analyzed for the association between diabetes and CI using a multiple linear regression analysis model. Using the same approach, we also analyzed the relationship between indicators of kidney injury/function and cognitive function (Animal Fluency Test, Digit Symbol Substitution Test) in the diabetic population. Results Diabetes was associated with CI. In age-adjusted model, older diabetics performed significantly poorer on tests of cognitive function compared to normoglycaemic individuals (1.145 points lower on the Animal Fluency Test (P = 0.005) and 7.868 points reduced on the Digit Symbol Substitution Test (P < 0.001)). In diabetics, we found elevated serum creatinine (SCr) (especially at SCr≥300uM) was associated with lower scores on cognitive function tests after strict adjustment for potential influences on cognitive function. While, albumin/creatinine ratio (ACR) was only associated with Digit Symbol Substitution score (DSS) not Animal Fluency score (AFS), and estimated glomerular filtration rate (eGFR) was only associated with CI (AFS and DSS) at the end-stage renal disease. Conclusion SCr, as a sensitive indicator of kidney injury, was significantly associated with CI and can potentially be used as an effective marker for screening CI in older diabetics.
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Affiliation(s)
- Yanhua Xiao
- Department of Rheumatology and Immunology, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Veda Devakumar
- Hiller Research Unit, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University, Düsseldorf, Germany
| | - Liyan Xu
- Department of Orthopaedics, Tianjin Hospital, Tianjin, China
| | - Lei Liu
- Department of Rheumatology and Immunology, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Hanyou Mo
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xuezhi Hong
- Department of Rheumatology and Immunology, Affiliated Hospital of Guilin Medical University, Guilin, China
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Nowak N, De Looze C, O’Halloran A, Kenny RA, Sexton DJ. The association between kidney function, cognitive function, and structural brain abnormalities in community-dwelling individuals aged 50+ is mediated by age and biomarkers of cardiovascular disease. Cardiovasc Res 2023; 119:2106-2116. [PMID: 37052588 PMCID: PMC10683948 DOI: 10.1093/cvr/cvad060] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 01/30/2023] [Accepted: 02/07/2023] [Indexed: 04/14/2023] Open
Abstract
AIMS Cognitive impairment has been associated with kidney function and chronic kidney disease. Whether this association is due to accelerated cardiovascular disease (CVD) or an independent specific kidney function effect related to toxins is unclear. We investigated the impact of an array of clinical factors, inflammatory biomarkers, and cardiovascular biomarkers on the association between kidney function, cognitive function, and structural brain abnormalities. METHODS AND RESULTS We used data from the first and third waves of the TILDA Study, a population-representative prospective cohort of Irish adults aged 50 years and over, based on stratified random sampling (n = 3774). The MRI sub-study included participants who consented to MRI brain imaging in addition to the health assessment. Multivariable linear and mixed-effect longitudinal regression models were fitted separately for each kidney marker/estimated glomerular filtration rate (eGFR) equation after adjusting for baseline age and demographics, clinical vascular risk factors, and biomarkers. Unadjusted analyses showed an association between low eGFR, cognitive dysfunction, and cognitive decline (P < 0.001 for all kidney markers). Kidney function markers were also associated with white matter disease [OR = 3.32 (95% CI: 1.11, 9.98)], total grey matter volume (β = -0.17, 95% CI -0.27 to -0.07), and regional grey matter volumes within areas particularly susceptible to hypoxia (P < 0.001 for all). All the associations decreased after adjusting for age and were also diminished after adjusting for CVD biomarkers. Age and CVD-biomarker score were significant mediators of the adjusted associations between eGFR and cognitive status. These results remained consistent for cross-sectional and longitudinal outcomes and specific cognitive domains. CONCLUSION Decreased kidney function was associated with cerebrovascular disease. The association appeared to be mediated predominantly by age and the combination of CVD markers [namely N-terminal pro-B-type natriuretic peptide (NT-proBNP) and Growth Differentiation Factor 15 (GDF15)], supporting the idea that shared biological pathways underline both diseases. Further mechanistic studies of the specific molecular mechanisms that lead to both kidney and cognitive decline are warranted.
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Affiliation(s)
- Natalia Nowak
- The Irish Longitudinal Study on Ageing, Trinity College Dublin, D02 R590, Dublin 2, Ireland
- School of Medicine, Trinity College Dublin, College Green, D02 PN40, Dublin 2, Ireland
| | - Celine De Looze
- The Irish Longitudinal Study on Ageing, Trinity College Dublin, D02 R590, Dublin 2, Ireland
- School of Medicine, Trinity College Dublin, College Green, D02 PN40, Dublin 2, Ireland
| | - Aisling O’Halloran
- The Irish Longitudinal Study on Ageing, Trinity College Dublin, D02 R590, Dublin 2, Ireland
- School of Medicine, Trinity College Dublin, College Green, D02 PN40, Dublin 2, Ireland
| | - Rose Anne Kenny
- The Irish Longitudinal Study on Ageing, Trinity College Dublin, D02 R590, Dublin 2, Ireland
- School of Medicine, Trinity College Dublin, College Green, D02 PN40, Dublin 2, Ireland
- Saint James Hospital, Dublin, D08 NYH1, Dublin 8, Ireland
| | - Donal J Sexton
- The Irish Longitudinal Study on Ageing, Trinity College Dublin, D02 R590, Dublin 2, Ireland
- School of Medicine, Trinity College Dublin, College Green, D02 PN40, Dublin 2, Ireland
- Saint James Hospital, Dublin, D08 NYH1, Dublin 8, Ireland
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Wang S, Lin X, Zhou J, Li M, Song D. Association between serum cystatin C level and cognition in older adults: a cross-sectional analysis. Front Neurosci 2023; 17:1200763. [PMID: 37207178 PMCID: PMC10188921 DOI: 10.3389/fnins.2023.1200763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Accepted: 04/13/2023] [Indexed: 05/21/2023] Open
Abstract
Introduction Serum Cystatin C level, an indication of kidney function, has been implicated in the pathogenesis of Alzheimer's disease and cognitive impairment. In this cross-sectional study, we looked into the relation between serum Cystatin C levels and cognition in a group of U.S. older adults. Method The data of this study were from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. A total of 4,832 older adults aged ≥60 who met the inclusion criteria were included. The Dade Behring N Latex Cystatin C assay, which is a particle-enhanced nephelometric assay (PENIA), was utilized to assess Cystatin C levels in participants' blood samples. Participants' cognition was examined using the digit symbol substitution test (DSST). Z-scores of the DSST were calculated based on sample means and standard deviations (SD). To investigate the relationships between the quartiles of serum Cystatin C level and DSST z scores, multiple linear regression models were developed while controlling for age, sex, race/ethnicity, and education. Results The average age of the participants was 71.1 (SD 7.8). The participants were about half female (50.5%), non-Hispanic White (61.2%), and (36.1%) who had completed at least some college. They had an average serum Cystatin C level of 1.0 mg/dl (SD 0.44). After performing multiple linear regression with a reference group consisting of participants in quartile one of plasma Cystatin C levels, we found that serum Cystatin C levels in quartiles three and four were independently associated with lower DSST z scores (β = -0.059, 95% CI -0.200 to -0.074 and β = -0.108, 95% CI -0.319 to -0.184, respectively). Conclusion Higher serum Cystatin C level is associated with worse processing speed, sustained attention, and working memory in older adults. Cystatin C level may be a biomarker for cognitive decline in older adults.
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Affiliation(s)
- Shuli Wang
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Xuechun Lin
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jie Zhou
- Department of Nursing, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, Guangdong, China
| | - Meng Li
- Kentucky STD Prevention and Control, Frankfort, KY, United States
| | - Dan Song
- Department of Nursing, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, Guangdong, China
- *Correspondence: Dan Song,
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9
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Demir N, Koz S, Ugurlu CT. Health literacy in chronic kidney disease patients: association with self-reported presence of acquaintance with kidney disease, disease burden and frequent contact with health care provider. Int Urol Nephrol 2022; 54:2295-2304. [PMID: 35122168 DOI: 10.1007/s11255-022-03124-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Accepted: 01/11/2022] [Indexed: 10/19/2022]
Abstract
BACKGROUND Limited data suggest that health literacy (HL) is associated with kidney functions and clinical outcomes in patients with non-dialysis chronic kidney disease (CKD). We aimed to identify factors associated with the level of HL in a CKD population that has not been studied previously. METHODS Patients with stage I-V (non-dialysis) CKD according to the Kidney Disease Outcomes Quality Initiative classification were enrolled in the study from two tertiary healthcare centers. Data were collected cross-sectionally using the European Health Literacy Survey (HLS-EU). RESULTS Data of 208 participants were analyzed. HLS-EU scores had the highest correlations with age (r = - 0.494, p = 0.0001) and education (r = 0.476, p = 0.0001). Estimated glomerular filtration rate (e-GFR) was significantly correlated with HLS-EU score (r = 0.186, p = 0.01). Presence of a self-reported acquaintance with any kind of kidney disease was associated with higher HL. On the other hand, participants with multiple comorbidities, and therefore with more frequent contact with the health system, had lower HL than those without such frequent contact. Similarly, those with a high disease burden had lower HL than those without. HLS-EU scores were also significantly associated with gender, marital status, occupational status, self-perception of health, restriction of daily activities, participation in social activities, place of residence, blood pressure, body mass index, and serum parathyroid hormone and albumin levels. CONCLUSION Low HL is prevalent among CKD patients and is associated with e-GFR. Presence of an acquaintance with any kind of kidney disease is positively associated with HL. Presence of multiple comorbidities might be a limiting factor for the improvement of HL, which might also be expected to improve as a result of frequent contact with healthcare providers.
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Affiliation(s)
- Nevgul Demir
- Department of Family Medicine, Ministry of the Health Kecioren Research and Education Hospital, Kecioren, Ankara, Turkey.
| | - Suleyman Koz
- Department of Nephrology, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkey
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10
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Tariq H, Ramakrishnan M, Gupta A. Insights into Cognitive Brain Health in Chronic Kidney Disease. GERONTOLOGY & GERIATRICS : RESEARCH 2022; 8:1074. [PMID: 37671071 PMCID: PMC10478617 DOI: 10.26420/gerontolgeriatrres.2022.1074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/07/2023]
Abstract
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.
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Affiliation(s)
- H Tariq
- Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, USA
| | - M Ramakrishnan
- Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, USA
| | - A Gupta
- Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, USA
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11
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Dyer AH, Laird E, Hoey L, Hughes CF, McNulty H, Ward M, Strain JJ, O’Kane M, Tracey F, Molloy AM, Cunningham C, Sexton DJ, McCarroll K. Reduced kidney function is associated with poorer domain-specific cognitive performance in community-dwelling older adults. Int J Geriatr Psychiatry 2022; 37:10.1002/gps.5771. [PMID: 35719039 PMCID: PMC9327725 DOI: 10.1002/gps.5771] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 06/01/2022] [Indexed: 11/11/2022]
Abstract
OBJECTIVES Whilst chronic kidney disease has been associated with cognitive impairment, the association between reduced estimated Glomerular Filtration Rate (eGFR) and domain-specific cognitive performance is less clear and may represent an important target for the promotion of optimal brain health in older adults. METHODS Participants aged >60 years from the Trinity-Ulster-Department of Agriculture study underwent detailed cognitive assessment using the Mini-Mental State Examination (Mini-Mental State Examination (MMSE)), Frontal Assessment Battery (FAB) and Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Poisson and linear regression models assessed the relationship between eGFR strata and cognitive performance. RESULTS In 4887 older adults (73.9 ± 8.3 years; 67.7% female), declining eGFR strata was associated with greater likelihood of error on the MMSE/FAB and poorer overall performance on the RBANS. Following robust covariate adjustment, findings were greatest for GFR <45 ml/ml/1.73 m2 (Incidence Rate Ratio: 1.17; 95% CI 1.08, 1.27; p < 0.001 for MMSE; IRR: 1.13; 95% CI 1.04, 1.13; p < 0.001 for FAB; β: -3.66; 95% CI -5.64, -1.86; p < 0.001 for RBANS). Additionally, eGFR <45 ml/ml/1.73 m2 was associated with poorer performance on all five RBANS domains, with greatest effect sizes for immediate memory, delayed memory and attention. Associations were strongest in those aged 60-70, with no associations observed in those >80 years. CONCLUSIONS Reduced kidney function was associated with poorer global and domain-specific neuropsychological performance. Associations were strongest with eGFR <45 ml/min/1.73 m2 and in those aged 60-70 years, suggesting that this population may potentially benefit from potential multi-domain interventions aimed at promoting optimal brain health in older adults.
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Affiliation(s)
- Adam H. Dyer
- Mercer's Institute for Successful AgeingSt James's HospitalDublinIreland,Wellcome‐HRB Clinical Research FacilitySt James's HospitalDublinIreland,Department of Medical GerontologySchool of MedicineTrinity College DublinDublinIreland
| | - Eamon Laird
- Department of Medical GerontologySchool of MedicineTrinity College DublinDublinIreland
| | - Leane Hoey
- The Nutrition Innovation Centre for Food and Health (NICHE)School of Biomedical SciencesUlster UniversityColeraineNorthern IrelandUK
| | - Catherine F. Hughes
- The Nutrition Innovation Centre for Food and Health (NICHE)School of Biomedical SciencesUlster UniversityColeraineNorthern IrelandUK
| | - Helene McNulty
- The Nutrition Innovation Centre for Food and Health (NICHE)School of Biomedical SciencesUlster UniversityColeraineNorthern IrelandUK
| | - Mary Ward
- The Nutrition Innovation Centre for Food and Health (NICHE)School of Biomedical SciencesUlster UniversityColeraineNorthern IrelandUK
| | - J. J. Strain
- The Nutrition Innovation Centre for Food and Health (NICHE)School of Biomedical SciencesUlster UniversityColeraineNorthern IrelandUK
| | - Maurice O’Kane
- Clinical Chemistry LaboratoryAltnagelvin HospitalWestern Health and Social Care TrustLondonderryNorthern IrelandUK
| | - Fergal Tracey
- Causeway HospitalNorthern Health and Social Care TrustColeraineNorthern IrelandUK
| | | | - Conal Cunningham
- Mercer's Institute for Successful AgeingSt James's HospitalDublinIreland,Wellcome‐HRB Clinical Research FacilitySt James's HospitalDublinIreland
| | - Donal J. Sexton
- Department of Medical GerontologySchool of MedicineTrinity College DublinDublinIreland,School of MedicineTrinity College DublinDublinIreland,Trinity Health Kidney CentreSchool of MedicineTrinity College DublinDublinIreland
| | - Kevin McCarroll
- Mercer's Institute for Successful AgeingSt James's HospitalDublinIreland,Department of Medical GerontologySchool of MedicineTrinity College DublinDublinIreland
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12
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Saad MA, Abo-Raya SN, Waly MA, Saad NL. Association of Serum Levels of Cystatin C and Cognition in a Cohort of Egyptian Elderly Patients with Chronic Kidney Disease. SAUDI JOURNAL OF KIDNEY DISEASES AND TRANSPLANTATION 2022; 33:288-295. [PMID: 37417181 DOI: 10.4103/1319-2442.379027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/08/2023] Open
Abstract
Chronic kidney disease (CKD) and dementia are common morbidities of elders. Serum cystatin C has been suggested to be an ideal marker for kidney function. The current study aimed to detect the serum levels of cystatin C in CKD patients and to correlate these levels to cognitive performance. The study involved 90 subjects aged 65 years and more, divided into two groups: Group 1: 60 patients with CKD, and Group 2: 30 control participants. Exclusion criteria included cardiac failure, hepatic failure, thyroid diseases, dialysis for more than one month, polycystic kidney disease, organ transplantation, and immunosuppressive therapy within the past six months. All participants had routine laboratory workup, serum cystatin C using enzyme-linked immunosorbent assay kits, and cognitive assessment using mini-mental state examination (MMSE). Serum cystatin level was significantly high in CKD patients while MMSE scores were significantly lower in CKD patients. A high significant negative correlation was found between serum cystatin C levels and both degree of cognitive impairment and glomerular filtration rate (GFR). Also, a significant positive correlation was found between the degree of cognitive impairment and GFR levels. Serum cystatin levels are significantly associated with cognitive impairment in CKD patients, and this correlation becomes more evident with the worsening of CKD stages. That may help in better understanding of the pathogenesis of dementia in CKD patients with the emergence of therapeutic options depending on these data.
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Affiliation(s)
- Marwa A Saad
- Department of Internal Medicine, Geriatric Unit, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Suzan N Abo-Raya
- Department of Internal Medicine, Geriatric Unit, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Marwa A Waly
- Department of Nephrology, Shark El-Madinah Hospital, Alexandria, Egypt
| | - Neveen L Saad
- Department of Clinical Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
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13
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Nair P, Misra S, Nath M, Vibha D, Srivastava AK, Prasad K, Kumar P. Cystatin C and Risk of Mild Cognitive Impairment: A Systematic Review and Meta-Analysis. Dement Geriatr Cogn Disord 2021; 49:471-482. [PMID: 33075778 DOI: 10.1159/000510219] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 07/14/2020] [Indexed: 12/29/2022] Open
Abstract
INTRODUCTION Cystatin C (Cys C) has been found as a novel biomarker of neurodegenerative diseases, such as dementia and Alzheimer's disease. Published studies on the role of Cys C as a biomarker of mild cognitive impairment (MCI) have not been reviewed systematically. OBJECTIVE Present meta-analysis was performed to elucidate the association between Cys C and risk of MCI. METHODS A comprehensive search was performed in PubMed, EMBASE, Cochrane Library, Trip databases, Worldwide Science, and Google Scholar from January 1, 1950, to April 30, 2020. Standardized mean difference (SMD) with 95% confidence interval (CI) using fixed or random effect models were used to calculate summary estimates. Quality of evidence was also assessed using the Diagnostic Accuracy Quality Scale (DAQS) and grading quality of evidence and strength of recommendations approach. RESULTS In our meta-analysis, 12 studies with a total of 2,433 MCI patients and 1,034 controls were included. Our findings suggest a strong association between increased levels of Cys C and risk of MCI as compared to control subjects (SMD = 2.39, 95% CI = 0.22-4.57). Subgroup analysis based on ethnicity, a significant association for the high level of Cys C with the risk of MCI was observed in the Asian population (SMD = 1.63, 95% CI = 0.44-2.82) but not in the Caucasian population (SMD = 2.80, 95% CI = [-0.66]-6.26). CONCLUSION Cys C was associated with MCI, and it could be considered as a predictor for the risk of cognitive impairment.
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Affiliation(s)
- Pallavi Nair
- Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
| | - Shubham Misra
- Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
| | - Manabesh Nath
- Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
| | - Deepti Vibha
- Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
| | | | - Kameshwar Prasad
- Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
| | - Pradeep Kumar
- Department of Neurology, All India Institute of Medical Sciences, New Delhi, India,
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14
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Wanggong F, Xiang J, Yang S, Zhang W, Tuerganbieke R. Correlation of serum uric acid, cystatin C and high-sensitivity C-reactive protein with cognitive impairment in lacunar cerebral infarction. Am J Transl Res 2021; 13:6717-6723. [PMID: 34306417 PMCID: PMC8290714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 11/22/2020] [Indexed: 06/13/2023]
Abstract
OBJECTIVE To study the correlation of serum uric acid (UA), cystatin C (Cys-C) and high-sensitivity C-reactive protein (hs-CRP) with cognitive impairment in lacunar cerebral infarction. METHODS Total 198 patients with lacunar cerebral infarction were selected and divided into 4 groups according to their cognitive function, with 65 cases in the normal group, 72 cases in the mild cognitive impairment group, 38 cases in the moderate cognitive impairment group and 23 cases in the severe cognitive impairment group. The hs-CRP, serum UA, Cys-C and Montreal Cognitive Assessment (MoCA) were measured upon admission. RESULTS There were statistical differences in hs-CRP, UA and Cys-C among the four groups (all P<0.001). MoCA was negatively correlated with hs-CRP, UA and Cys-C (all P<0.001). Multivariate logistic regression analysis showed that elevated levels of hs-CRP, UA and Cys-C were the influencing factors of cognitive impairment in patients with lacunar cerebral infarction (all P<0.05). CONCLUSION The levels of hs-CRP, UA and Cys-C in patients with lacunar cerebral infarction increase with the aggravation of cognitive impairment, and high hs-CRP, UA and Cys-C are independent risk factors of cognitive impairment in patients with lacunar cerebral infarction.
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Affiliation(s)
- Fenfei Wanggong
- Department of Neurology, Xinhua Hospital of Ily Kazakh Autonomous PrefectureIly, Xinjiang Uygur Autonomous Region, China
| | - Jianfeng Xiang
- Department of Interventional Oncology, Renji Hospital, Shanghai Jiao Tong University School of MedicineShanghai City, China
| | - Shichen Yang
- Department of Neurology, The People’s Hospital of Xinyuan CountyIly, Xinjiang Uygur Autonomous Region, China
| | - Weilan Zhang
- General Medicine, Shanghai Fengxian District Central Hospital (South Campus, Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University)Shanghai City, China
| | - Reziya Tuerganbieke
- Department of Neurology, The People’s Hospital of Zhaosu CountyIly, Xinjiang Uygur Autonomous Region, China
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15
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Ma S, Zhang M, Liu Y, Ding D, Li P, Ma X, Liu H, Mu J. Abnormal rich club organization in end-stage renal disease patients before dialysis initiation and undergoing maintenance hemodialysis. BMC Nephrol 2020; 21:515. [PMID: 33243163 PMCID: PMC7689979 DOI: 10.1186/s12882-020-02176-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 11/18/2020] [Indexed: 11/25/2022] Open
Abstract
Background End-stage renal disease (ESRD) patients are at a substantially higher risk for developing cognitive impairment compared with the healthy population. Dialysis is an essential way to maintain the life of ESRD patients. Based on previous research, there isn’t an uncontested result whether cognition was improved or worsened during dialysis. Methods To explore the impact of dialysis treatment on cognitive performance, we recruited healthy controls (HCs), predialysis ESRD patients (predialysis group), and maintenance hemodialysis ESRD patients (HD group). All ESRD patients performed six blood biochemistry tests (hemoglobin, urea, cystatin C, Na+, K+, and parathyroid hormone). Neuropsychological tests were used to measure cognitive function. By using diffusion tensor imaging and graph-theory approaches, the topological organization of the whole-brain structural network was investigated. Generalized linear models (GLMs) were performed to investigate blood biochemistry predictors of the neuropsychological tests and the results of graph analyses in the HD group and predialysis group. Results Neuropsychological analysis showed the HD group exhibited better cognitive function than the predialysis group, but both were worse than HCs. Whole-brain graph analyses revealed that increased global efficiency and normalized shortest path length remained in the predialysis group and HD group than the HCs. Besides, a lower normalized clustering coefficient was found in the predialysis group relative to the HCs and HD group. For the GLM analysis, only the Cystatin C level was significantly associated with the average fiber length of rich club connections in the predialysis group. Conclusions Our study revealed that dialysis had a limited effect on cognitive improvement.
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Affiliation(s)
- Shaohui Ma
- Department of Medical Imaging, First Affiliated Hospital of Xi'an Jiaotong University, No. 277, West Yanta Road, Xi'an, 710061, Shaanxi-Province, People's Republic of China
| | - Ming Zhang
- Department of Medical Imaging, First Affiliated Hospital of Xi'an Jiaotong University, No. 277, West Yanta Road, Xi'an, 710061, Shaanxi-Province, People's Republic of China
| | - Yang Liu
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, 710126, People's Republic of China.,Engineering Research Center of Molecular & Neuroimaging, Ministry of Education, Xi'an, 710126, People's Republic of China
| | - Dun Ding
- Department of Medical Imaging, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China
| | - Peng Li
- Department of Medical Imaging, First Affiliated Hospital of Xi'an Jiaotong University, No. 277, West Yanta Road, Xi'an, 710061, Shaanxi-Province, People's Republic of China.,Department of Medical Imaging, Shaanxi Nuclear Geology 215 Hospital, Xianyang, People's Republic of China
| | - Xueying Ma
- The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010000, People's Republic of China
| | - Hongjuan Liu
- Department of Medical Imaging, First Affiliated Hospital of Xi'an Jiaotong University, No. 277, West Yanta Road, Xi'an, 710061, Shaanxi-Province, People's Republic of China.
| | - Junya Mu
- Center for Brain Imaging, School of Life Science and Technology, Xidian University, Xi'an, 710126, People's Republic of China. .,Engineering Research Center of Molecular & Neuroimaging, Ministry of Education, Xi'an, 710126, People's Republic of China. .,School of Life Science and Technology, Xidian University, Xi'an, 710071, People's Republic of China.
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16
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Tollitt J, Odudu A, Montaldi D, Kalra PA. Cognitive impairment in patients with moderate to severe chronic kidney disease: the Salford kidney cohort study. Clin Kidney J 2020; 14:1639-1648. [PMID: 34084459 PMCID: PMC8162857 DOI: 10.1093/ckj/sfaa178] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 07/20/2020] [Indexed: 12/24/2022] Open
Abstract
Background Cognitive 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. Method A 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. Results About 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). Conclusion Risk 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.
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Affiliation(s)
- James Tollitt
- Renal Department, Salford Royal NHS Trust, Salford, UK.,Institute of Cardiovascular Sciences, University of Manchester, Oxford Road, Manchester, UK
| | - Aghogho Odudu
- Institute of Cardiovascular Sciences, University of Manchester, Oxford Road, Manchester, UK.,Renal Department, Manchester Foundation Trust, Manchester, UK
| | - Daniela Montaldi
- Department for Memory Neurosciences, University of Manchester, Oxford Road, Manchester, UK
| | - Philip A Kalra
- Renal Department, Salford Royal NHS Trust, Salford, UK.,Institute of Cardiovascular Sciences, University of Manchester, Oxford Road, Manchester, UK
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17
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Pierpaoli E, Fabi K, Lenci FF, Ricci M, Di Rosa M, Onder G, Volpato S, Ruggiero C, Cherubini A, Corsonello A, Lattanzio F. Kidney function and cognitive impairment among older hospitalized patients: a comparison of four glomerular filtration rate equations. Aging Clin Exp Res 2020; 32:841-850. [PMID: 31732959 DOI: 10.1007/s40520-019-01405-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2019] [Accepted: 10/30/2019] [Indexed: 11/30/2022]
Abstract
BACKGROUND The relationship between the estimated glomerular filtration rate (eGFR) and cognitive impairment may change as a function of the equation used. We aimed at investigating the association between four different eGFR equations and cognitive impairment among older hospitalized patients. METHODS Our series consisted of 795 older patients consecutively admitted to 7 geriatric and internal medicine acute care wards. The eGFR was calculated by Chronic Kidney Disease Epidemiologic Collaboration (CKD-EPI), Cockcroft-Gault (CG), Berlin Initiative Study (BIS) and Full Age Spectrum (FAS) equations. Study outcomes were total Mini Mental State Examination (MMSE) < 24 and sub-scores related to orientation to time, orientation to space, registration, calculation, three words recall, language and constructional praxis. Statistical analysis was carried out by logistic or Poisson regressions when appropriate. The accuracy of eGFR equations in identifying cognitive outcomes was investigated by calculating the area (AUC) under the receiver operating characteristic (ROC) curve for each equation. RESULTS After adjusting for potential confounders, eGFR < 30 was significantly associated with MMSE < 24 only with CKD-EPI equation (OR 2.03, 95% CI 1.04-3.96). eGFR < 30 was significantly associated with constructional apraxia with all study equations (CKD-EPI: OR 3.62, 95% CI 1.73-7.56; BIS: OR 2.86, 95% CI 1.31-6.26; FAS: OR 2.83, 95% CI 1.44-5.56; CG: OR 2.08, 95% CI 1.09-3.99). The accuracy of eGFR < 30 in identifying patients with defective constructional praxis was poor with all (BIS: AUC 0.54, 95% CI 0.52-0.55; CKD-EPI: AUC 0.55, 95% CI 0.53-0.57; CG: AUC 0.58, 95% CI 0.55-0.61; FAS: AUC 0.56, 95% CI 0.54-0.58). CONCLUSIONS Constructional apraxia may characterize the cognitive profile of older patients with severe CKD. The accuracy in identifying patients with constructional apraxia is only fair, and studies including other biomarkers of kidney function are needed.
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Affiliation(s)
- Elisa Pierpaoli
- Advanced Technology Center for Aging Research, Scientific Technological Area, IRCCS INRCA, Ancona, Italy
| | - Katia Fabi
- Unit of Neurology, IRCCS INRCA, Ancona, Italy
| | | | | | - Mirko Di Rosa
- Unit of Geriatric Pharmacoepidemiology and Biostatistics, IRCCS INRCA, Ancona and Cosenza, Via Santa Margherita 5, 60124, Ancona, Italy.
| | - Graziano Onder
- Department of Cardiovascular and endocrine-metabolic diseases, and aging, Istituto Superiore di Sanità, Rome, Italy
| | - Stefano Volpato
- Department of Medical Sciences, Section of Internal and Cardiorespiratory Medicine, University of Ferrara, Ferrara, Italy
| | - Carmelinda Ruggiero
- Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy
| | - Antonio Cherubini
- Geriatria, Accettazione geriatrica e Centro di Ricerca per l'Invecchiamento, IRCCS INRCA, Ancona, Italy
| | - Andrea Corsonello
- Unit of Geriatric Pharmacoepidemiology and Biostatistics, IRCCS INRCA, Ancona and Cosenza, Via Santa Margherita 5, 60124, Ancona, Italy
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Stephan Y, Sutin AR, Terracciano A. Subjective Age and Cystatin C Among Older Adults. J Gerontol B Psychol Sci Soc Sci 2020; 74:382-388. [PMID: 29045722 DOI: 10.1093/geronb/gbx124] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Accepted: 09/15/2017] [Indexed: 01/10/2023] Open
Abstract
OBJECTIVE Cystatin C (CysC) is a marker of kidney function that is relevant for the health and cognition of older adults. Little is known about the link between psychological factors and CysC. Therefore, the present study examined whether subjective age is related to CysC level and changes in CysC over time. METHOD Participants were 5,066 individuals drawn from the Health and Retirement Study aged from 50 to 107 years (60% women, mean age = 69.36 years, SD = 9.54). They provided data on subjective age, demographic covariates, and CysC at baseline. CysC was assessed again 4 years later. RESULTS Analysis revealed that an older subjective age was related to higher level of CysC at baseline and to an increase in CysC over 4 years, controlling for demographic factors. An older subjective age was also related to higher risk of exceeding the clinical threshold of CysC at baseline and 4 years later. Additional analysis revealed that disease burden, depressive symptoms, physical inactivity, and BMI partly mediated these associations. CONCLUSION The present study provides new evidence on the role of subjective age as a psychological factor associated with individuals' risk of kidney dysfunction, an association beyond chronological age.
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Affiliation(s)
| | - Angelina R Sutin
- Department of Behavioral Sciences and Social Medicine, Florida State University, Tallahassee
| | - Antonio Terracciano
- Department of Geriatrics, College of Medicine, Florida State University, Tallahassee
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Cui Z, Cao G, Wang Y, Ma Q, Wang C, Xu Y, Sun H, Ma Y. Effects of Cystatin C on Cognitive Impairment in Older Chinese Adults. Am J Alzheimers Dis Other Demen 2020; 35:1533317520965101. [PMID: 33111545 PMCID: PMC10624069 DOI: 10.1177/1533317520965101] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/03/2024]
Abstract
OBJECTIVE To find a suitable dividing value to classify cystatin C and evaluate the association between cognition and levels of cystatin C. METHODS Using data from the China Health and Retirement Longitudinal Study, We conducted a longitudinal analysis of a prospective cohort of 6,869 middle-aged and older Chinese without cognitive impairment at baseline. Levels of cystatin C were categorized into 2 groups by method of decision tree. Logistic regression models evaluated whether cystatin C was related to cognitive impairment. RESULTS Respondents were categorized as lower levels of cystatin C and higher levels of cystatin C, cut-point was 1.11 mg/L. Higher levels of cystatin C was associated with the odds of cognitive impairment (OR, 1.56; 95% CI, 1.10-2.22) after multivariable adjustment. Respondents with higher levels of cystatin C had worse cognition scores. CONCLUSIONS We found a suitable dividing value of cystatin C in middle-aged and older Chinese.
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Affiliation(s)
- Zhizhen Cui
- Department of Child Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, People’s Republic of China
| | - Guizhen Cao
- Department of Child Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, People’s Republic of China
| | - Youyi Wang
- Department of Child Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, People’s Republic of China
| | - Qinghua Ma
- The 3rd People’s Hospital of Xiangcheng District, Suzhou, People’s Republic of China
| | - Congju Wang
- Centers for Disease Control and Prevention of Suzhou High-tech Zone, Suzhou, People’s Republic of China
| | - Yong Xu
- Department of Child Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, People’s Republic of China
| | - Hongpeng Sun
- Department of Child Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, People’s Republic of China
| | - Yana Ma
- Department of Child Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, People’s Republic of China
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Abstract
The Systolic Blood Pressure Intervention Trial is the first large prospective randomized controlled trial to demonstrate the benefit of an intensive systolic blood pressure (SBP) treatment target (<120 mm Hg) compared to a standard target (<140 mm Hg) in reducing cardiovascular morbidity and mortality and all-cause mortality in high-risk hypertensive patients. The impact of SPRINT on hypertension treatment has been large, but major questions remain about the feasibility of achieving the SPRINT intensive SBP target in routine practice, the generalizability of the SPRINT findings to hypertensive populations that were excluded from the trial, and the cost effectiveness of adopting the SPRINT intensive treatment goal. In this review, we discuss the generalizability of SPRINT data to the general population of adults with hypertension and with various comorbidities, the cost effectiveness of intensive SBP-lowering therapy, and the implications of SPRINT for future hypertension guideline development and clinical practice.
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Affiliation(s)
- Lama Ghazi
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota 55455;
| | - Suzanne Oparil
- Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama 35294;
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Zeng Q, Huang Z, Wei L, Fang J, Lin K. Correlations of serum cystatin C level and gene polymorphism with vascular cognitive impairment after acute cerebral infarction. Neurol Sci 2019; 40:1049-1054. [PMID: 30805744 DOI: 10.1007/s10072-019-03777-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2018] [Accepted: 02/16/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND The aim of this study was to explore the possible correlations of serum cystatin C level and cystatin C gene (CST3) polymorphism with vascular cognitive impairment in patients who had acute cerebral infarction. METHODS A total of 152 patients with acute cerebral infarction were recruited in this case-control study. Patients were divided into vascular cognitive impairment (VCI) group (n = 71) and cognitive impairment no dementia (CIND) group (n = 81). The serum concentrations of cystatin C were measured with immunoturbidimetric assay while the gene polymorphisms of CST3 were determined by technique polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS In the VCI group, serum cystatin C level was significantly higher than that in the control group. The frequency of the B allele was found to be higher in the VCI group as compared with that of the CIND group (18.5% vs 7.7%, p = 0.006). In logistic regression analysis, significant associations of VCI with high serum cystatin C level (OR 3.837 (1.176-12.520), p = 0.026) and CST3 B allele (OR 2.038 (1.048-3.963), p = 0.036) were also found. CONCLUSIONS A high cystatin C level and CST3 B allele confer risks for VCI after acute cerebral infarction. It is probable that measurement of the serum cystatin C level and detection of CST3 gene polymorphism would aid in the early diagnosis of VCI, but further studies are warranted.
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Affiliation(s)
- Qiong Zeng
- Department of Neurology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Zhihua Huang
- Shantou University Medical College, Shantou, China
| | - Liling Wei
- Department of Neurology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Jingnian Fang
- Department of Neurology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Kun Lin
- Department of Endocrinology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
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Gunasekaran V, Dey S, Chakrawarty A, Chatterjee P, Sati HC, Dwivedi SN, Dey AB. Raised serum cystatin C can be a potential biomarker of frailty detected by cumulative deficit model. Aging Med (Milton) 2018; 1:149-153. [PMID: 31942492 PMCID: PMC6880677 DOI: 10.1002/agm2.12038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Revised: 08/14/2018] [Accepted: 08/14/2018] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVE Identification of frailty by clinical criteria is often delayed to the advanced stage. A reliable biomarker to identify frailty or its risk does not currently exist. We aimed to determine the association between serum cystatin C and frailty in subjects without renal dysfunction. METHODS We carried out a cross-sectional observational study in the Department of Geriatric Medicine, All India Institute of Medical Sciences, New Delhi, India. The study involved 125 participants, aged 65 years or older. Frailty status was assessed with Frailty Index criteria (cumulative deficit model). Serum cystatin C was estimated with the nephelometry method and its association with frailty was analyzed. RESULTS Mean age of the study sample was 76.32 years with 72 (57.6%) male and 53 (42.4%) female participants. Seventy-three subjects were frail; the mean cystatin C levels in the frail and non-frail groups were 1.28 mg/L (±0.39) and 1.12 mg/L (±0.27), respectively, and the difference was significant (P < 0.05). A cutoff of 1.12 mg/L was found to be 60.27% sensitive and 57.69% specific in identification of frailty. Multivariate analysis showed that higher cystatin C level was associated with 2.52 (1.05-6.02) times the risk of being frail. CONCLUSION Higher levels of cystatin C were found in frail subjects. Cystatin C seems to be a promising marker for identifying frailty in older adults without renal abnormalities.
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Affiliation(s)
| | - Sharmistha Dey
- Department of BiophysicsAll India Institute of Medical SciencesNew DelhiIndia
| | - Avinash Chakrawarty
- Department of Geriatric MedicineAll India Institute of Medical SciencesNew DelhiIndia
| | - Prashun Chatterjee
- Department of Geriatric MedicineAll India Institute of Medical SciencesNew DelhiIndia
| | - Hem Chandra Sati
- Department of BiostatisticsAll India Institute of Medical SciencesNew DelhiIndia
| | - Sada Nand Dwivedi
- Department of BiostatisticsAll India Institute of Medical SciencesNew DelhiIndia
| | - Aparajit Ballav Dey
- Department of Geriatric MedicineAll India Institute of Medical SciencesNew DelhiIndia
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Hebebrand J, Peters T, Schijven D, Hebebrand M, Grasemann C, Winkler TW, Heid IM, Antel J, Föcker M, Tegeler L, Brauner L, Adan RAH, Luykx JJ, Correll CU, König IR, Hinney A, Libuda L. The role of genetic variation of human metabolism for BMI, mental traits and mental disorders. Mol Metab 2018; 12:1-11. [PMID: 29673576 PMCID: PMC6001916 DOI: 10.1016/j.molmet.2018.03.015] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Revised: 03/23/2018] [Accepted: 03/29/2018] [Indexed: 12/30/2022] Open
Abstract
OBJECTIVE The aim was to assess whether loci associated with metabolic traits also have a significant role in BMI and mental traits/disorders METHODS: We first assessed the number of single nucleotide polymorphisms (SNPs) with genome-wide significance for human metabolism (NHGRI-EBI Catalog). These 516 SNPs (216 independent loci) were looked-up in genome-wide association studies for association with body mass index (BMI) and the mental traits/disorders educational attainment, neuroticism, schizophrenia, well-being, anxiety, depressive symptoms, major depressive disorder, autism-spectrum disorder, attention-deficit/hyperactivity disorder, Alzheimer's disease, bipolar disorder, aggressive behavior, and internalizing problems. A strict significance threshold of p < 6.92 × 10-6 was based on the correction for 516 SNPs and all 14 phenotypes, a second less conservative threshold (p < 9.69 × 10-5) on the correction for the 516 SNPs only. RESULTS 19 SNPs located in nine independent loci revealed p-values < 6.92 × 10-6; the less strict criterion was met by 41 SNPs in 24 independent loci. BMI and schizophrenia showed the most pronounced genetic overlap with human metabolism with three loci each meeting the strict significance threshold. Overall, genetic variation associated with estimated glomerular filtration rate showed up frequently; single metabolite SNPs were associated with more than one phenotype. Replications in independent samples were obtained for BMI and educational attainment. CONCLUSIONS Approximately 5-10% of the regions involved in the regulation of blood/urine metabolite levels seem to also play a role in BMI and mental traits/disorders and related phenotypes. If validated in metabolomic studies of the respective phenotypes, the associated blood/urine metabolites may enable novel preventive and therapeutic strategies.
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Affiliation(s)
- Johannes Hebebrand
- Department of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Triinu Peters
- Department of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Dick Schijven
- Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Moritz Hebebrand
- Department of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Corinna Grasemann
- Pediatric Endocrinology and Diabetology, Klinik für Kinderheilkunde II, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Thomas W Winkler
- Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany
| | - Iris M Heid
- Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany
| | - Jochen Antel
- Department of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Manuel Föcker
- Department of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Lisa Tegeler
- Department of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Lena Brauner
- Department of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Roger A H Adan
- Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Jurjen J Luykx
- Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Psychiatry, ZNA Hospitals, Antwerp, Belgium
| | - Christoph U Correll
- Division of Psychiatry Research, Northwell Health, The Zucker Hillside Hospital, Glen Oaks, NY, USA
| | - Inke R König
- Institute of Medical Biometry and Statistics, University of Luebeck, Luebeck, Schleswig-Holstein, Germany
| | - Anke Hinney
- Department of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Lars Libuda
- Department of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
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Alaini A, Malhotra D, Rondon-Berrios H, Argyropoulos CP, Khitan ZJ, Raj DSC, Rohrscheib M, Shapiro JI, Tzamaloukas AH. Establishing the presence or absence of chronic kidney disease: Uses and limitations of formulas estimating the glomerular filtration rate. World J Methodol 2017; 7:73-92. [PMID: 29026688 PMCID: PMC5618145 DOI: 10.5662/wjm.v7.i3.73] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 05/17/2017] [Accepted: 05/30/2017] [Indexed: 02/06/2023] Open
Abstract
The development of formulas estimating glomerular filtration rate (eGFR) from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity, gender and age, has led to the current scheme of diagnosing and staging chronic kidney disease (CKD), which is based on eGFR values and albuminuria. This scheme has been applied extensively in various populations and has led to the current estimates of prevalence of CKD. In addition, this scheme is applied in clinical studies evaluating the risks of CKD and the efficacy of various interventions directed towards improving its course. Disagreements between creatinine-based and cystatin-based eGFR values and between eGFR values and measured GFR have been reported in various cohorts. These disagreements are the consequence of variations in the rate of production and in factors, other than GFR, affecting the rate of removal of creatinine and cystatin C. The disagreements create limitations for all eGFR formulas developed so far. The main limitations are low sensitivity in detecting early CKD in several subjects, e.g., those with hyperfiltration, and poor prediction of the course of CKD. Research efforts in CKD are currently directed towards identification of biomarkers that are better indices of GFR than the current biomarkers and, particularly, biomarkers of early renal tissue injury.
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Affiliation(s)
- Ahmed Alaini
- Division of Nephrology, Department of Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131, United States
| | - Deepak Malhotra
- Division of Nephrology, Department of Medicine, University of Toledo School of Medicine, Toledo, OH 43614-5809, United States
| | - Helbert Rondon-Berrios
- Renal and Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, United States
| | - Christos P Argyropoulos
- Division of Nephrology, Department of Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131, United States
| | - Zeid J Khitan
- Division of Nephrology, Department of Medicine, Joan C. Edwards School of Medicine, Huntington, WV 25701, United States
| | - Dominic S C Raj
- Division of Nephrology, Department of Medicine, George Washington University, Washington, DC 20037, United States
| | - Mark Rohrscheib
- Division of Nephrology, Department of Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131, United States
| | - Joseph I Shapiro
- Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25701, United States
| | - Antonios H Tzamaloukas
- Nephrology Section, Medicine Service, Raymond G. Murphy VA Medical Center, Albuquerque, NM 87108, United States
- Department of Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87108, United States
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Yuen T, Brouillette MJ, Fellows LK, Ellis RJ, Letendre S, Heaton R, The CHARTER group, Mayo N. Personalized Risk Index for Neurocognitive Decline Among People With Well-Controlled HIV Infection. J Acquir Immune Defic Syndr 2017; 76:48-54. [PMID: 28797021 PMCID: PMC12077807 DOI: 10.1097/qai.0000000000001466] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Little is known about the predictors of neurocognitive decline in HIV+ individuals with good virological control. Identification of modifiable risk factors would allow targeted interventions to reduce the risk of decline in higher risk individuals. The objective of this study was to develop a risk index to predict neurocognitive decline over 3 years in aviremic HIV+ individuals. METHODS As part of the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study, HIV+ adults completed clinical evaluation and neuropsychological tests every 6 months. Group-based trajectory analysis was used to detect patterns of neurocognitive change; individuals who deteriorated ≥ 0.5 SD on at least one neuropsychological test were considered decliners. Multiple logistic regression was used to identify baseline sociodemographic, clinical, biological, and lifestyle factors associated with decline in the subgroup that was consistently aviremic during the first 3 years. A risk index was developed using the beta-coefficients from the final regression model. RESULTS Neurocognitive decline occurred in 23 of 191 (12%) participants followed longitudinally. The baseline factors that predicted decline were glomerular filtration rate ≤50 mL/min, known duration of HIV infection ≥15 years, education ≤12 years, and cerebrospinal fluid protein >45 mg/dL. CONCLUSIONS Using this analytic approach, neurocognitive decline was uncommon in this sample of aviremic HIV+ individuals. The 3-year risk of decline ranged from 2% in those with no risk factors to 95% in those with all 4. The strongest predictor was glomerular filtration rate, also a predictor of cardiovascular disease. This raises the possibility that controlling vascular risk factors could reduce the risk of neurocognitive decline.
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Affiliation(s)
- Tracy Yuen
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Québec, Canada
- Division of Clinical Epidemiology, McGill University Health Center, Montreal, Québec, Canada
| | - Marie-Josée Brouillette
- Chronic Viral Illness Service, McGill University Health Centre and Department of Psychiatry, McGill University, Montreal, Québec, Canada
| | - Lesley K. Fellows
- Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Québec, Canada
| | - Ronald J. Ellis
- Department of Neurosciences, University of California San Diego, San Diego, CA
- Department of Psychiatry, University of California San Diego, San Diego, CA
| | - Scott Letendre
- Department of Psychiatry, University of California San Diego, San Diego, CA
- HIV Neurobehavioural Research Centre, University of California San Diego, San Diego, CA
| | - Robert Heaton
- Department of Psychiatry, University of California San Diego, San Diego, CA
- HIV Neurobehavioural Research Centre, University of California San Diego, San Diego, CA
| | | | - Nancy Mayo
- Division of Clinical Epidemiology, McGill University Health Center, Montreal, Québec, Canada
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Impact of cystatin C and microalbuminuria on cognitive impairment in the population of community-dwelling Japanese. Atherosclerosis 2017; 265:71-77. [PMID: 28865325 DOI: 10.1016/j.atherosclerosis.2017.08.022] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Revised: 08/16/2017] [Accepted: 08/23/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Cognitive impairment is an important element affecting our well-being, and as such, early diagnosis is critical today. We investigated whether serum cystatin C and microalbuminuria are associated with cognitive impairment. METHODS A total of 1943 subjects (774 males, 1169 females, mean age 65.8 years) took part in the investigation, and underwent a health examination in Tanushimaru, Japan, in 2009. The participants' cognitive function was evaluated using of mini-mental state examination (MMSE). We measured the levels of serum cystatin C using latex nephelometric immunoassay. Spot urine samples were used to measure microalbuminuria levels. Multivariate linear regression analyses were used to assess the relationship between MMSE scores and the level of cystatin C or microalbuminuria. All statistical analyses were performed using the SAS system. RESULTS The mean values of log-transformed serum cystatin C levels and log-transformed microalbuminuria were 0.95 (range 0.41-7.11) mg/L and 10.7 (range 1.1-2600) mg/g·Cr, respectively. The means of MMSE score were 27.7 ± 2.5. In the multivariate linear regression analyses adjusted for age and sex, MMSE was significantly associated with systolic blood pressure (p = 0.024, inversely), cystatin C (p = 0.046, inversely) and microalbuminuria (p = 0.019, inversely), whereas estimated glomerular filtration rate (eGFR) had an insignificant association (p = 0.197). In the multiple stepwise linear regression analysis, age, history of stroke, systolic blood pressure, serum cystatin C were independently associated with MMSE levels. CONCLUSIONS We demonstrated for the first time that cognitive function was significantly and inversely associated with cystatin C and microalbuminuria, in the relatively younger general population.
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O’Connell ME, Tuokko H, Voll S, Simard M, Griffith LE, Taler V, Wolfson C, Kirkland S, Raina P. An evidence-based approach to the creation of normative data: base rates of impaired scores within a brief neuropsychological battery argue for age corrections, but against corrections for medical conditions. Clin Neuropsychol 2017; 31:1188-1203. [DOI: 10.1080/13854046.2017.1349931] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
| | - Holly Tuokko
- Institute on Aging & Lifelong Health, University of Victoria, Victoria, Canada
| | - Stacey Voll
- Institute on Aging & Lifelong Health, University of Victoria, Victoria, Canada
| | - Martine Simard
- School of Psychology, Laval University and Centre de recherche de l’Institut universitaire en santé mentale de Québec, Québec City, Canada
| | - Lauren E. Griffith
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
| | - Vanessa Taler
- School of Psychology, University of Ottawa & Bruyère Research Institute, Ottawa, Canada
| | - Christina Wolfson
- Department of Epidemiology and Biostatistics and Occupational Health, McGill University, Montreal, Canada
| | - Susan Kirkland
- Department of Community Health and Epidemiology, Dalhousie University, Halifax, Canada
| | - Parminder Raina
- Faculty of Health Sciences, Department of Health Research Methods, Evidence and Impact, McMaster Institute for Research on Aging & Labarge Centre for Mobility in Aging, McMaster University, Hamilton, Canada
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Weiner DE, Gaussoin SA, Nord J, Auchus AP, Chelune GJ, Chonchol M, Coker L, Haley WE, Killeen AA, Kimmel PL, Lerner AJ, Oparil S, Saklayen MG, Slinin YM, Wright CB, Williamson JD, Kurella Tamura M. Cognitive Function and Kidney Disease: Baseline Data From the Systolic Blood Pressure Intervention Trial (SPRINT). Am J Kidney Dis 2017; 70:357-367. [PMID: 28606731 DOI: 10.1053/j.ajkd.2017.04.021] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Accepted: 04/13/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND Chronic kidney disease is common and is associated with cardiovascular disease, cerebrovascular disease, and cognitive function, although the nature of this relationship remains uncertain. STUDY DESIGN Cross-sectional cohort using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT). SETTING & PARTICIPANTS Participants in SPRINT, a randomized clinical trial of blood pressure targets in older community-dwelling adults with cardiovascular disease, chronic kidney disease, or high cardiovascular disease risk and without diabetes or known stroke, who underwent detailed neurocognitive testing in the cognition substudy, SPRINT-Memory and Cognition in Decreased Hypertension (SPRINT-MIND). PREDICTORS Urine albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). OUTCOMES Cognitive function, a priori defined as 5 cognitive domains based on 11 cognitive tests using z scores, and abnormal white matter volume quantified by brain magnetic resonance imaging. RESULTS Of 9,361 SPRINT participants, 2,800 participated in SPRINT-MIND and 2,707 had complete data; 637 had brain imaging. Mean age was 68 years, 37% were women, 30% were black, and 20% had known cardiovascular disease. Mean eGFR was 70.8±20.9mL/min/1.73m2 and median urine ACR was 9.7 (IQR, 5.7-22.5) mg/g. In adjusted analyses, higher ACR was associated with worse global cognitive function, executive function, memory, and attention, such that each doubling of urine ACR had the same association with cognitive performance as being 7, 10, 6, and 14 months older, respectively. Lower eGFR was independently associated with worse global cognitive function and memory. In adjusted models, higher ACR, but not eGFR, was associated with larger abnormal white matter volume. LIMITATIONS Cross-sectional only, no patients with diabetes were included. CONCLUSIONS In older adults, higher urine ACR and lower eGFR have independent associations with global cognitive performance with different affected domains. Albuminuria concurrently identifies a higher burden of abnormal brain white matter disease, suggesting that vascular disease may mediate these relationships.
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Affiliation(s)
| | - Sarah A Gaussoin
- Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC
| | - John Nord
- University of Utah and George E. Wahlen VAMC, Salt Lake City, UT
| | | | | | | | - Laura Coker
- Department of Social Sciences and Health Policy, Wake Forest University School of Medicine, Winston-Salem, NC
| | | | | | - Paul L Kimmel
- National Institutes of Health, National Institute of Diabetes Digestive and Kidney Diseases, Bethesda, MD
| | - Alan J Lerner
- Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, OH
| | | | | | - Yelena M Slinin
- Minneapolis Veteran's Administration Healthcare System and University of Minnesota, Minneapolis, MN
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Mora-Gutiérrez JM, Slon Roblero MF, Castaño Bilbao I, Izquierdo Bautista D, Arteaga Coloma J, Martínez Velilla N. [Chronic kidney disease in the elderly patient]. Rev Esp Geriatr Gerontol 2017; 52:152-158. [PMID: 27161192 DOI: 10.1016/j.regg.2016.03.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2016] [Revised: 03/13/2016] [Accepted: 03/15/2016] [Indexed: 06/05/2023]
Abstract
Chronic kidney disease (CKD) is widely prevalent worldwide, with a special impact on elderly population. Around half of people aged over 75 meet diagnostic criteria for CKD according to the recent 'Kidney disease improving global outcomes' (KDIGO) 2012 clinical practice guideline on the evaluation and management of CKD. However, geriatric patients have characteristics that may not be addressed by general guidelines. Therefore, it is important to know the natural history of the disease, symptoms, and 'red-flags' that could help in the management of these patients. In this review, a complete approach is presented on the pathophysiology, diagnosis, and treatment of CKD in the geriatric population.
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Affiliation(s)
- José María Mora-Gutiérrez
- Servicio de Nefrología, Clínica Universidad de Navarra, Pamplona, España; Instituto de Investigación Sanitaria de Navarra (IdiSNa), Pamplona, España.
| | | | | | | | | | - Nicolás Martínez Velilla
- Servicio de Geriatría, Complejo Hospitalario de Navarra, Pamplona, España; Red de Investigación en Servicios Sanitarios en Enfermedades Crónicas (REDISSEC), España; Instituto de Investigación Sanitaria de Navarra (IdiSNa), Pamplona, España
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Wei Y, Wei YK, Zhu J. Early markers of kidney dysfunction and cognitive impairment among older adults. J Neurol Sci 2017; 375:209-214. [PMID: 28320132 DOI: 10.1016/j.jns.2017.01.071] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Revised: 01/19/2017] [Accepted: 01/30/2017] [Indexed: 02/01/2023]
Abstract
BACKGROUND Age-related decline in kidney function can be an important risk factor for cognitive impairment in older adults. In this study, we examined several kidney function measures for the association with cognitive function in older adults in hope to identify early and sensitive markers that can be used for the detection or screening for cognitive impairment. METHODS A total of 1982 older participants (aged ≥60years) in the 1999-2002 National Health and Nutrition Examination Survey was analyzed for the association between kidney function and cognitive impairment using multivariate logistic regression and general linear models. Cognitive functioning was assessed during the household interview using a version of the Digit Symbol Substitution Test of the Wechsler Adult Intelligence Scale III. In our study, participants with a score of <31, the 25th percentiles of the distribution, or who were unable to complete the sample exercise due to cognitive limitations were classified as having cognitive impairment. RESULTS Of 1982 older adults, 503 were having cognitive impairment (weighted prevalence, 15.38%). Among the kidney function measures that we examined, the levels of serum cystatin C and urinary albumin were found being significantly associated with cognitive impairment after adjusting for age, sex, race/ethnicity, poverty status, education, physical activity, BMI, cigarette smoking, and alcohol consumption. Cognitive functioning scores were significantly decreasing with increasing levels of kidney dysfunction markers. CONCLUSION Serum cystatin C and urinary albumin that are early markers of chronic kidney disease might serve as early and effective markers for cognitive decline in older adults. Mechanisms underlying the observed association need to be further characterized.
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Affiliation(s)
- Yudan Wei
- Department of Community Medicine, Mercer University School of Medicine, Macon, GA, USA.
| | - Yinan Kevin Wei
- Medical College of Georgia, Augusta University, Augusta, GA, USA
| | - Jianmin Zhu
- Department of Mathematics and Computer Science, Fort Valley State University, Fort Valley, GA, USA
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Shen Z, Ruan Q, Yu Z, Sun Z. Chronic kidney disease-related physical frailty and cognitive impairment: a systemic review. Geriatr Gerontol Int 2017; 17:529-544. [PMID: 27240548 DOI: 10.1111/ggi.12758] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Accepted: 01/12/2016] [Indexed: 11/28/2022]
Abstract
AIM The objective of this review was to assess chronic kidney disease-related frailty and cognitive impairment, as well as their probable causes, mechanisms and the interventions. METHODS Studies from 1990 to 2015 were reviewed to evaluate the relationship between chronic kidney disease and physical frailty and cognitive impairment. Of the 1694 studies from the initial search, longitudinal studies (n = 22) with the keywords "Cognitive and CKD" and longitudinal or cross-sectional studies (n = 5) with the keywords "Frailty and CKD" were included in final analysis. RESULTS By pooling current research, we show clear evidence for a relationship between chronic kidney disease and frailty and cognitive impairment in major studies. Vascular disease is likely an important mediator, particularly for cognitive impairment. However, non-vascular factors also play an important role. Many of the other mechanisms that contribute to impaired cognitive function and increased frailty in CKD remain to be elucidated. In limited studies, medication therapy did not obtain the ideal effect. There are limited data on treatment strategies, but addressing the vascular disease risk factors earlier in life might decrease the subsequent burden of frailty and cognitive impairment in this population. Multidimensional interventions, which address both microvascular health and other factors, may have substantial benefits for both the cognitive impairments and physical frailty in this vulnerable population. CONCLUSIONS Chronic kidney disease is a potential cause of frailty and cognitive impairment. Vascular and non-vascular factors are the possible causes. The mechanism of chronic kidney disease-induced physical frailty and cognitive impairment suggests that multidimensional interventions may be effective therapeutic strategies in the early stage of chronic kidney disease. Geriatr Gerontol Int 2017; 17: 529-544.
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Affiliation(s)
- Zhiyuan Shen
- Department of Urology, Huadong Hospital, Fudan University, 221 West Yan'an Road, Shanghai, China
| | - Qingwei Ruan
- Shanghai Institute of Geriatrics and Gerontology, Shanghai Key Laboratory of Clinical Geriatrics, Department of Geriatrics, Huadong Hospital, and Research Center of Aging and Medicine, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhuowei Yu
- Shanghai Institute of Geriatrics and Gerontology, Shanghai Key Laboratory of Clinical Geriatrics, Department of Geriatrics, Huadong Hospital, and Research Center of Aging and Medicine, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhongquan Sun
- Department of Urology, Huadong Hospital, Fudan University, 221 West Yan'an Road, Shanghai, China
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Chronic Kidney Disease and Subclinical Brain Infarction Increase the Risk of Vascular Cognitive Impairment: The Sefuri Study. J Stroke Cerebrovasc Dis 2017; 26:420-424. [DOI: 10.1016/j.jstrokecerebrovasdis.2016.10.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2016] [Revised: 09/27/2016] [Accepted: 10/02/2016] [Indexed: 11/15/2022] Open
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Yin Z, Yan Z, Liang Y, Jiang H, Cai C, Song A, Feng L, Qiu C. Interactive effects of diabetes and impaired kidney function on cognitive performance in old age: a population-based study. BMC Geriatr 2016; 16:7. [PMID: 26753625 PMCID: PMC4710025 DOI: 10.1186/s12877-016-0193-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Accepted: 01/08/2016] [Indexed: 12/21/2022] Open
Abstract
Background The interactive effect between diabetes and impaired kidney function on cognitive impairment in older adults has not yet been reported. The aim of this study was to investigate the association of diabetes and impaired kidney function with cognitive impairment among Chinese older people living in a rural area. Methods This cross-sectional study included 1,358 participants (age ≥60 years; 60.5 % women) in the population-based Confucius Hometown Aging Project in Shandong, China. Data on demographics, lifestyle factors, health history, use of medications, global cognitive function, and kidney function were collected through structured interviews, clinical examinations, and blood tests. We defined diabetes as a fasting plasma glucose level ≥7.0 mmol/l or use of hypoglycemic agents, impaired kidney function as glomerular filtration rate estimated from cystatin C (eGFRcys) <60 ml/min/1.73 m2. Cognitive impairment was defined using the education-based cut-off scores of Mini-Mental State Examination (MMSE). Data were analyzed using multiple general linear and logistic regression models. Results Cognitive impairment was defined in 197 (14.5 %) persons. The multi-adjusted β coefficient of MMSE score associated with diabetes was −0.06 (95 % confidence interval [CI], −0.16, 0.03); the corresponding figures associated with eGFRcys <60, 60–89.9, and ≥90 ml/min/1.73 m2 were −0.15 (−0.28, −0.02), −0.01 (−0.10, 0.08), and 0 (reference) (Ptrend = 0.046), respectively. Diabetes and impaired kidney function showed an interactive effect on cognitive impairment (Pinteraction = 0.02). Compared with individuals having neither diabetes nor impaired kidney function, those with both conditions had a multi-adjusted odds ratio of 4.23 (95 % CI, 2.10–8.49) for cognitive impairment. The relative excess risk due to interaction was 2.74. Conclusions This study suggests that concurrent presence of diabetes and impaired kidney function is associated with a substantial likelihood for cognitive impairment in older adults.
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Affiliation(s)
- Zhaoxue Yin
- Division of Non-communicable Diseases Control and Community Health, Chinese Center for Disease Control and Prevention, Beijing, China.
| | - Zhongrui Yan
- Department of Neurology, Jining No. 1 People's Hospital, Shandong, China.
| | - Yajun Liang
- School of Public Health, Jining Medical University, Shandong, China. .,Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University, Stockholm, Sweden.
| | - Hui Jiang
- Xing Long Zhuang Hospital, Yankuang Group, Shandong, China.
| | - Chuanzhu Cai
- Xing Long Zhuang Hospital, Yankuang Group, Shandong, China.
| | - Aiqin Song
- School of Public Health, Jining Medical University, Shandong, China.
| | - Lei Feng
- Department of Psychological Medicine, National University of Singapore, NUHS Tower Block, 1E Kent Ridge Road, Singapore, Singapore.
| | - Chengxuan Qiu
- Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University, Stockholm, Sweden.
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Arnold R, Issar T, Krishnan AV, Pussell BA. Neurological complications in chronic kidney disease. JRSM Cardiovasc Dis 2016; 5:2048004016677687. [PMID: 27867500 PMCID: PMC5102165 DOI: 10.1177/2048004016677687] [Citation(s) in RCA: 104] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Revised: 09/16/2016] [Accepted: 09/21/2016] [Indexed: 01/12/2023] Open
Abstract
Patients with chronic kidney disease (CKD) are frequently afflicted with neurological complications. These complications can potentially affect both the central and peripheral nervous systems. Common neurological complications in CKD include stroke, cognitive dysfunction, encephalopathy, peripheral and autonomic neuropathies. These conditions have significant impact not only on patient morbidity but also on mortality risk through a variety of mechanisms. Understanding the pathophysiological mechanisms of these conditions can provide insights into effective management strategies for neurological complications. This review describes clinical management of neurological complications in CKD with reference to the contributing physiological and pathological derangements. Stroke, cognitive dysfunction and dementia share several pathological mechanisms that may contribute to vascular impairment and neurodegeneration. Cognitive dysfunction and dementia may be differentiated from encephalopathy which has similar contributing factors but presents in an acute and rapidly progressive manner and may be accompanied by tremor and asterixis. Recent evidence suggests that dietary potassium restriction may be a useful preventative measure for peripheral neuropathy. Management of painful neuropathic symptoms can be achieved by pharmacological means with careful dosing and side effect considerations for reduced renal function. Patients with autonomic neuropathy may respond to sildenafil for impotence. Neurological complications often become clinically apparent at end-stage disease, however early detection and management of these conditions in mild CKD may reduce their impact at later stages.
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Affiliation(s)
- Ria Arnold
- School of Medical Sciences, University of New South Wales, Sydney, Australia
| | - Tushar Issar
- Prince of Wales Clinical School, University of New South Wales, Sydney, Australia
| | - Arun V Krishnan
- Prince of Wales Clinical School, University of New South Wales, Sydney, Australia
| | - Bruce A Pussell
- Prince of Wales Clinical School, University of New South Wales, Sydney, Australia
- Bruce A Pussell, Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales 2052, Australia.
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Slinin Y, Peters KW, Ishani A, Yaffe K, Fink HA, Stone KL, Steffes M, Ensrud KE. Cystatin C and cognitive impairment 10 years later in older women. J Gerontol A Biol Sci Med Sci 2014; 70:771-8. [PMID: 25362662 DOI: 10.1093/gerona/glu189] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2014] [Accepted: 09/08/2014] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Results of prospective studies examining the association between cystatin C and incident cognitive impairment have been inconsistent. We tested the hypothesis that there is a U-shaped association in older women between cystatin C and risk of incident cognitive impairment 10 years later. METHODS We conducted a longitudinal analysis of a prospective cohort of 1,332 community-dwelling elderly women without dementia at baseline who had baseline cystatin C and serum creatinine measurements and completed an extended cognitive battery of neuropsychological tests with determination of cognitive status 10 years later. Incident cognitive impairment was defined as either new onset of adjudicated diagnosis of mild cognitive impairment or dementia. RESULTS Incident mild cognitive impairment or dementia was identified among 140 (26.0%) women in quartile 1 (Q1), 122 (22.6%) in Q2, 121 (22.5%) in Q3, and 156 (28.9%) in Q4 of cystatin C. In the fully adjusted model, compared to women in Q2-Q3 of cystatin C, adjusted odds ratios (95% CI) for incident cognitive impairment were 1.31 (0.98-1.75) for Q1, and 1.25 (0.94-1.66) for Q4 Compared to women in Q2-Q3 of estimated glomerular filtration rate (eGFRCysC), adjusted odds ratios (95% CI) for incident cognitive impairment after 10 years of follow-up were 1.18 (0.88-1.58) for Q4 (eGFRCysC 76.1-109.4mL/min/1.73 m(2)) and 1.26 (0.94-1.67) for Q1 (eGFRCysC 21.8-55.5mL/min/1.73 m(2)). CONCLUSIONS These results support a U-shaped association between cystatin C concentration and risk of cognitive impairment or dementia 10 years later, but the association is not independent of potential confounding factors.
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Affiliation(s)
- Yelena Slinin
- Department of Medicine, University of Minnesota, Minneapolis. Department of Medicine, Minneapolis VA Health Care System, Minnesota.
| | | | - Areef Ishani
- Department of Medicine, University of Minnesota, Minneapolis. Department of Medicine, Minneapolis VA Health Care System, Minnesota
| | - Kristine Yaffe
- Department of Psychiatry, Neurology, and Epidemiology & Biostatistics, University of California, San Francisco
| | - Howard A Fink
- Department of Medicine, University of Minnesota, Minneapolis. Department of Medicine, Minneapolis VA Health Care System, Minnesota. Division of Epidemiology & Community Health and
| | - Katie L Stone
- California Pacific Medical Center Research Institute, San Francisco
| | - Michael Steffes
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis
| | - Kristine E Ensrud
- Department of Medicine, University of Minnesota, Minneapolis. Department of Medicine, Minneapolis VA Health Care System, Minnesota. Division of Epidemiology & Community Health and
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Recent publications by ochsner authors. Ochsner J 2014; 14:724-30. [PMID: 25598740 PMCID: PMC4294413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/04/2023] Open
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