Chronic kidney disease biomarkers, cognitive impairment and incident dementia in an older healthy cohort

Background: Chronic kidney disease is a risk factor for cognitive impairment (CI),but reports of individual associations of estimated glomerular filtration rate (eGFR) and albuminuria with CI and incident dementia in healthier older longitudinal populations are lacking. Our goal was to estimate these associations in a large cohort of older healthy persons. Methods: In a longitudinal cohort study of older persons without prior cardiovascular disease, we estimated the associations between baseline eGFR (in mL/min per 1.73 m2) and albuminuria, measured as urine albumin-to-creatinine ratio (UACR, in mg/mmol) and cognitive test scores, declines in cognitive test scores and incident dementia, using adjusted linear and linear mixed models. Cox proportional hazards regression models assessed the association between baseline kidney function and incident CI no dementia (CIND) or dementia at a median of 4.7 years. Results: At baseline, among 18,131 participants, median age was 74 years, eGFR 74 (IQR 63, 84), UACR 0.8 (IQR 0.5, 1.5; (7.1 (4.4- 13.3 mg/g and 56% were female. Baseline eGFR was not associated with performance on any cognitive tests in cross-sectional analysis, nor incident CIND or dementia over median follow-up of 4.7 years. However, baseline UACR ≥ 3 (≥ 26.6 mg/g) was significantly associated with lower baseline scores and larger declines on the Modified Mini Mental State Exam, verbal memory and processing speed tests, and with incident CIND [(hazard ratio, HR, 1.19; 95% confidence interval, CI,1.07 - 1.33)] and dementia (HR 1.32;1.06 - 1.66). Conclusion: Mild albuminuria was associated with worse baseline cognitive function, cognitive decline, and increased risk for incident CIND and dementia. Screening global cognitive tests for older persons with UACR ≥ 3 mg/mmol could identify those at elevated risk of cognitive decline and dementia.

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Cognitive Impairment, Chronic Kidney Disease, and 1-Year Mortality in Older Patients Discharged from Acute Care Hospital

Journal of Clinical Medicine ◽

10.3390/jcm9072202 ◽

2020 ◽

Vol 9 (7) ◽

pp. 2202

Author(s):

Mirko Di Rosa ◽

Sonia D’Alia ◽

Francesco Guarasci ◽

Luca Soraci ◽

Elisa Pierpaoli ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Cognitive Impairment ◽

Kidney Disease ◽

Older Patients ◽

Cox Regression ◽

Acute Care Hospital ◽

Potential Interaction ◽

Care Hospital ◽

Increased Risk ◽

Constructional Apraxia

The prognostic interaction between chronic kidney disease (CKD) and cognitive impairment is still to be elucidated. We investigated the potential interaction of overall cognitive impairment or defective constructional praxis and CKD in predicting 1-year mortality among 646 older patients discharged from hospital. The estimated glomerular filtration rate (eGFR) was calculated using the Berlin Initiative Study (BIS) equation. Cognitive impairment was assessed by the Mini Mental State Exam (MMSE) and defective constructional praxis was ascertained by the inherent MMSE item. The study outcome was 1-year mortality. Statistical analysis was carried out using Cox regression. After adjusting for potential confounders, the co-occurrence of eGFR <30 and overall cognitive impairment (Hazard Ratio (HR) = 3.12, 95% Confidence Interval (CI) = 1.26–7.77) and defective constructional praxis (HR = 2.50, 95% CI = 1.08–5.77) were associated with the outcome. No significant prognostic interaction of eGFR < 30 with either overall cognitive impairment (HR = 1.99, 95% CI = 0.38–10.3) or constructional apraxia (HR = 1.68, 95% CI = 0.33–8.50) was detectable, while only cognitive deficits were found significantly associated with the outcome in the interaction models (HR = 3.12, 95% CI = 1.45–6.71 for overall cognitive impairment and HR = 2.16, 95% CI = 1.05–4.45 for constructional apraxia). Overall cognitive impairment and defective constructional praxis may be associated with increased risk of 1-year mortality among older hospitalized patients with severe CKD. However, no significant prognostic interaction between CKD and cognitive impairment could be observed.

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Cognitive Impairment in Chronic Kidney Disease: Vascular Milieu and the Potential Therapeutic Role of Exercise

BioMed Research International ◽

10.1155/2017/2726369 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 21

Author(s):

Ulf G. Bronas ◽

Houry Puzantian ◽

Mary Hannan

Keyword(s):

Quality Of Life ◽

Chronic Kidney Disease ◽

Cognitive Impairment ◽

Kidney Disease ◽

Physical Function ◽

Vascular Dysfunction ◽

Therapeutic Modality ◽

Increased Risk

Chronic kidney disease (CKD) is considered a model of accelerated aging. More specifically, CKD leads to reduced physical functioning and increased frailty, increased vascular dysfunction, vascular calcification and arterial stiffness, high levels of systemic inflammation, and oxidative stress, as well as increased cognitive impairment. Increasing evidence suggests that the cognitive impairment associated with CKD may be related to cerebral small vessel disease and overall impairment in white matter integrity. The triad of poor physical function, vascular dysfunction, and cognitive impairment places patients living with CKD at an increased risk for loss of independence, poor health-related quality of life, morbidity, and mortality. The purpose of this review is to discuss the available evidence of cerebrovascular-renal axis and its interconnection with early and accelerated cognitive impairment in patients with CKD and the plausible role of exercise as a therapeutic modality. Understanding the cerebrovascular-renal axis pathophysiological link and its interconnection with physical function is important for clinicians in order to minimize the risk of loss of independence and improve quality of life in patients with CKD.

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Correlation Between Cognitive Function Impairment and Chronic Kidney Disease With a Low Glomerular Filtration Rate at Sanglah Hospital Denpasar

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2020.4691 ◽

2020 ◽

Vol 8 (B) ◽

pp. 752-756

Author(s):

Anak Agung Ayu Putri Laksmidewi ◽

Cok Istri Gangga Dewi Dewi ◽

Yennny Kandarini

Keyword(s):

Chronic Kidney Disease ◽

Glomerular Filtration Rate ◽

Cognitive Impairment ◽

Cognitive Function ◽

Kidney Disease ◽

Glomerular Filtration ◽

Filtration Rate ◽

Control Group ◽

Case Group ◽

Increased Risk

BACKGROUND: Chronic kidney disease is a condition of chronic kidney damage with abnormal structure and function of the kidneys that lasts more than 3 months, accompanied or not by a decrease in glomerular filtration rate. Organic kidney disease leaves accumulated organic waste that cannot be removed by the kidneys. Furthermore, several biochemical and metabolic mechanisms such as chronic inflammation and oxidative stress can cause executive disorders. AIM: The aim of the study was to find out an increased risk of impaired cognitive function in patients with chronic kidney disease with a low glomerular filtration rate in Sanglah Hospital. METHOD: This study uses a retrospective case–control analytic observational study design. We included all patients with chronic kidney disease in Sanglah Hospital in December 2017–January 2018. This study involved 46 subjects with chronic kidney disease who met eligibility criteria, classified as a case group with cognitive impairment and a control group without cognitive impairment. RESULTS: Each decrease in glomerular filtration rate < 30 ml/min/173 m2 in patients with chronic renal failure correlates with an increased incidence of cognitive impairment of around 15–25%. The risk of chronic kidney disease patients with glomerular filtration rate < 30 ml/min/1.73 m2 decreased cognitive function 13 times compared to subjects with glomerular filtration rate > 30 ml/min/ 1.73 m2. CONCLUSION: Low glomerular filtration rate correlate with increased risk of cognitive impairment.

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Long‐Term Blood Pressure Variability and Risk of Cognitive Decline and Dementia Among Older Adults

Journal of the American Heart Association ◽

10.1161/jaha.120.019613 ◽

2021 ◽

Author(s):

Michael E. Ernst ◽

Joanne Ryan ◽

Enayet K. Chowdhury ◽

Karen L. Margolis ◽

Lawrence J. Beilin ◽

...

Keyword(s):

Blood Pressure ◽

Older Adults ◽

Cognitive Impairment ◽

Cognitive Decline ◽

Blood Pressure Variability ◽

Link Type ◽

Incident Dementia ◽

Increased Risk ◽

The Impact

Background Blood pressure variability (BPV) in midlife increases risk of late‐life dementia, but the impact of BPV on the cognition of adults who have already reached older ages free of major cognitive deficits is unknown. We examined the risk of incident dementia and cognitive decline associated with long‐term, visit‐to‐visit BPV in a post hoc analysis of the ASPREE (Aspirin in Reducing Events in the Elderly) trial. Methods and Results ASPREE participants (N=19 114) were free of dementia and significant cognitive impairment at enrollment. Measurement of BP and administration of a standardized cognitive battery evaluating global cognition, delayed episodic memory, verbal fluency, and processing speed and attention occurred at baseline and follow‐up visits. Time‐to‐event analysis using Cox proportional hazards regression models were used to calculate hazard ratios (HR) and corresponding 95% CI for incident dementia and cognitive decline, according to tertile of SD of systolic BPV. Individuals in the highest BPV tertile compared with the lowest had an increased risk of incident dementia and cognitive decline, independent of average BP and use of antihypertensive drugs. There was evidence that sex modified the association with incident dementia (interaction P =0.02), with increased risk in men (HR, 1.68; 95% CI, 1.19–2.39) but not women (HR, 1.01; 95% CI, 0.72–1.42). For cognitive decline, similar increased risks were observed for men and women (interaction P =0.15; men: HR, 1.36; 95% CI, 1.16–1.59; women: HR, 1.14; 95% CI, 0.98–1.32). Conclusions High BPV in older adults without major cognitive impairment, particularly men, is associated with increased risks of dementia and cognitive decline. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01038583; isrctn.com . Identifier: ISRCTN83772183.

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Nitride oxide synthase 3 and klotho gene polymorphisms in the pathogenesis of chronic kidney disease and age-related cognitive impairment: a systematic review and meta-analysis

F1000Research ◽

10.12688/f1000research.22989.2 ◽

2021 ◽

Vol 9 ◽

pp. 252

Author(s):

Atma Gunawan ◽

Jonny Karunia Fajar ◽

Fredo Tamara ◽

Aditya Indra Mahendra ◽

Muhammad Ilmawan ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Cognitive Impairment ◽

Kidney Disease ◽

Meta Analysis ◽

Initial Assessment ◽

Age Related ◽

Increased Risk ◽

Nitride Oxide ◽

Oxide Synthase ◽

Increased Susceptibility

Background: While it has been known that the development of chronic kidney disease (CKD) and age-related cognitive impairment involves several mediators, the evidence in clinical practice only reveals nitride oxide synthase (NOS) and klotho. However, the evidence for this topic is conflicted. The aim of this study was to assess the role of NOS and klotho single nucleotide polymorphisms (SNPs) in the pathogenesis of CKD and age-related cognitive impairment. Methods: We performed a meta-analysis during October to December 2019. Paper collection was performed in major scientific websites, and we extracted information of interest from each paper. Data were analyzed using a Z-test with either random or fixed effect model. Results: Our initial assessment identified NOS3 G894T, NOS3 T786C, NOS3 4b/4a, klotho (KL) G395A, and KL C1818T as the gene candidate for our meta-analysis. Our pooled calculation revealed that NOS3 G894T was associated with the risk of both age-related cognitive impairment and CKD. Increased susceptibility to age-related cognitive impairment was observed in the GG genotype, and increased risk of CKD was found in patients with a single T allele and TT genotype for NOS3 nucleotide 894. For NOS3 4b/4a, increased risk of CKD was only found in 4a4a genotype. For NOS3 T786C, we failed to show the association with both CKD and age-related cognitive impairment. Subsequently, for KL G395A, A allele and GA genotype were found to correlate with increased susceptibility to CKD, while its correlation to age-related cognitive impairment was failed to clarify. For KL C1818T, our analysis failed to find the correlation with the risk of CKD. Conclusions: Our results reveal that the NOS3 G894T gene polymorphism has a crucial role in the pathogenesis of both CKD and age-related cognitive impairment.

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Examining the Combined Estimated Effects of Hearing Impairment and Depression on Cognitive Decline and Dementia

Innovation in Aging ◽

10.1093/geroni/igab046.1848 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 480-480

Author(s):

Danielle Powell ◽

Willa Brenowitz ◽

Kristine Yaffe ◽

Frank Lin ◽

Alden Gross ◽

...

Keyword(s):

Older Adults ◽

Hearing Loss ◽

Depressive Symptoms ◽

Cognitive Decline ◽

Cox Proportional Hazards ◽

Hearing Impaired ◽

Cognitive Test ◽

Late Life Depression ◽

Incident Dementia ◽

Increased Risk

Abstract Late-life depression is a comorbidity which may co-occur in older adults with hearing loss- each as prevalent and independent modifiable risk factors for dementia. We used data from 1,820 participants (74 ± 2.8 years, 38% Black race) from the Health Aging and Body Composition Study to test if the hearing loss-dementia/cognitive decline (Modified Mini Mental State Exam[3MS] and Digit Symbol Substitution[DSST]) relationship differed in hearing impaired participants who also had depressive symptoms. Depressive symptoms were defined as CES-D 10 ≥10) at one or more visits from years 1-5. Algorithmic incident dementia defined using medication use, hospitalizations and cognitive test scores. Audiometric hearing loss was measured at year 5 and categorized as normal/mild vs ≥moderate loss. In linear mixed models adjusted for demographic and clinical covariates, presence of both hearing loss and depressive symptoms (vs. having neither) was associated with faster rates of decline in 3MS (-0.30, 95% CI:-0.78, -0.19) and DSST (-0.35,95% CI:-0.67, -0.03) over 10 years of follow-up. Both hearing loss and depressive symptoms (vs. neither) was associated with increased risk (hazard ratio (HR):2.91, 95%CI: 1.59, 5.33) of incident dementia in multivariable-adjusted Cox proportional hazards models. Comorbid conditions among hearing impaired older adults should be considered and may aid in dementia prevention and management strategies.

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Cognitive impairment in patients with moderate to severe chronic kidney disease: the Salford kidney cohort study

Clinical Kidney Journal ◽

10.1093/ckj/sfaa178 ◽

2020 ◽

Author(s):

James Tollitt ◽

Aghogho Odudu ◽

Daniela Montaldi ◽

Philip A Kalra

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Cognitive Impairment ◽

Kidney Disease ◽

Vascular Disease ◽

Older Age ◽

Cognitive Assessments ◽

Previous Stroke ◽

Increased Risk ◽

Severe Chronic Kidney Disease

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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MO531IMPACT OF INFLAMMATORY MARKERS IN COGNITIVE IMPAIRMENT IN CHRONIC KIDNEY DISEASE PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab087.0051 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Merita Rroji (Molla) ◽

Larisa Shehaj ◽

Myftar Barbullushi

Keyword(s):

Chronic Kidney Disease ◽

Cognitive Impairment ◽

Cognitive Function ◽

Kidney Disease ◽

Inflammatory Markers ◽

Routine Practice ◽

Increased Risk ◽

Ckd Stage ◽

The Mean ◽

Hs Crp

Abstract Background and Aims Cognitive impairment is an increasingly identified major cause of chronic disability and is commonly found in patients with chronic kidney disease (CKD). Knowledge of the link between kidney dysfunction and impaired cognition may enhance our understanding of risk factors impacting cognitive dysfunction. Our study aimed to evaluate the relation between serum inflammatory markers and the risk of cognitive decline among adults with CKD. Method Forty-six patients predialysis patients CKD stage 5 (mean age 55.6±11.5 years old) accepted to participate in the study. The Montreal Cognitive Assessment (MoCA) scale was administered to patients. Patients with a MoCA global score of 24/30 were considered cognitively impaired. Descriptive analysis was done for the socio-demographic and clinical variables. We measured high-sensitivity C-reactive protein (hs-CRP), ferritin level, albuminemia, and fibrinogen in baseline plasma samples. Results The mean total MoCA score for all the patients was 22.9 ±3.8 points. Thirty-seven patients, 57.7%, were evaluated with CI, where 74.6 % with Mild CI (MCI) and 25.4% with severe CI (SCI) under 20 points). MoCA subscale analysis revealed that the mean score for visuospatial/executive domain and attention were the lowest with 5.41±1.1 /8max and 2.93±1.75/6 max, and scores for orientation were the highest 5.92±0.57/6 max. At baseline, higher levels of each inflammatory marker were associated with poorer age-adjusted performance. In analyses adjusted for baseline cognition, demographics, comorbid conditions, and kidney function, participants in the highest tertile of hs-CRP, the highest tertile of fibrinogen, and the highest tertile of ferritin had an increased risk of impairment in attention compared to participants in the lowest tertile of each marker (p=0.043, p=0.047, p=0.029, respectively. The high level of ferritin was evaluated as a risk of impairment visuospatial/executive ability, and no relationship of inflammatory markers was observed with impairment of orientation p=0.01. hs-CRP and ferritin and low albumin level were independently associated with longitudinal global cognitive function (p=0.04, p=0.02, p=0.49 respectively). Conclusion In CKD patients, we have a relatively high risk for cognitive impairment. Our results extend the findings from prior studies by showing that inflammatory markers used in routine practice contribute and are independently associated with longitudinal changes in some domains of cognitive function in patients with CKD going in parallel with the inflammatory mechanisms that have been implicated in the pathogenesis of vascular and Alzheimer’s dementia.

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