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The Brain in Kidney Disease (BRINK) Cohort Study: Design and Baseline Cognitive Function.

ABSTRACT: The Brain in Kidney Disease (BRINK) Study aims to identify mechanisms that contribute to increased risk for cognitive impairment in patients with chronic kidney disease (CKD). We describe the rationale, design, and methods of the study and report baseline recruitment and cognitive function results.Longitudinal observational cohort study of the epidemiology of cognitive impairment in CKD. The primary aim is to characterize the association between (1) baseline and incident stroke, white matter disease, estimated glomerular filtration rate (eGFR), inflammation, microalbuminuria, and dialysis initiation and (2) cognitive decline over 3 years in a CKD cohort with a mean eGFR<45 mL/min/1.73 m(2).Community-dwelling participants 45 years or older recruited from 4 health systems into 2 groups: reduced eGFR, defined as eGFR<60 mL/min/1.73 m(2) (non-dialysis dependent), and control, defined as eGFR?60 mL/min/1.73 m(2).eGFR group.Performance on cognitive function tests and structural brain magnetic resonance imaging.Sequential cognitive and physical function testing, serum and urine biomarker measurement, and brain magnetic resonance images over 3 years.Of 554 participants, mean age was 69.3 years; 333, 88, and 133 had eGFRs<45 (non-dialysis dependent, nontransplantation), 45 to <60, and ?60 (controls) mL/min/1.73 m(2), respectively. Mean eGFR in reduced-eGFR participants was 34.3 mL/min/1.73 m(2). Baseline cognitive performance was significantly associated with eGFR in all domains except language. Participants with eGFRs<30 mL/min/1.73 m(2) performed significantly worse than those with eGFRs?30 mL/min/1.73 m(2) on tests of memory, processing speed, and executive function. Participants with reduced eGFRs overall scored worst on the Immediate Brief Visual-Spatial Memory Test-Revised.Healthy cohort bias, competing risk for death versus cognitive decline.Cognitive function was significantly worse in participants with eGFRs<30 mL/min/1.73 m(2). Future BRINK analyses will measure risk factors for cognitive decline using the longitudinal data.

SUBMITTER: Murray AM

PROVIDER: S-EPMC5271565 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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The Brain in Kidney Disease (BRINK) Cohort Study: Design and Baseline Cognitive Function.

Murray Anne M AM Bell Elizabeth J EJ Tupper David E DE Davey Cynthia S CS Pederson Sarah L SL Amiot Elizabeth M EM Miley Kathleen M KM McPherson Lauren L Heubner Brooke M BM Gilbertson David T DT Foley Robert N RN Drawz Paul E PE Slinin Yelena Y Rossom Rebecca C RC Lakshminarayan Kamakshi K Vemuri Prashanthi P Jack Clifford R CR Knopman David S DS

American journal of kidney diseases : the official journal of the National Kidney Foundation 20151229 4

<h4>Background</h4>The Brain in Kidney Disease (BRINK) Study aims to identify mechanisms that contribute to increased risk for cognitive impairment in patients with chronic kidney disease (CKD). We describe the rationale, design, and methods of the study and report baseline recruitment and cognitive function results.<h4>Study design</h4>Longitudinal observational cohort study of the epidemiology of cognitive impairment in CKD. The primary aim is to characterize the association between (1) baseli ...[more]

PMID: 26744128

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Project description:The risk of dementia increases in patients with cognitive impairment. However, it is not clear what factors contribute to the onset of dementia in those with cognitive impairment. In this prospective cohort study, we will investigate the every-five-year incidence of cognitive impairment and prognostic factors for cognitive impairment. The Jidong cognitive impairment cohort was established from April 2012 to August 2015, during which we recruited 5854 healthy participants (55.1% male) older than 45 years (mean, 57 years). Participants received a health examination in the Staff Hospital, Jidong Oilfield Branch, China National Petroleum Corporation. Baseline data and blood samples were collected. Cognitive impairment was evaluated using the Mini-Mental State Examination, and was defined as a Mini-Mental State Examination score of less than 24. Dementia was assessed using the criteria of Diagnostic and Statistical Manual of Mental Disorders (Fourth edition), the International Working Group criteria, and the Mini-Mental State Examination score. The follow-up will continue until December 2024, during which a prognostic model will be constructed. The primary outcome is the presence/absence of dementia and the secondary outcome is quality of life. Baseline screening results showed the following: (1) Cognitive impairment was apparent in 320 participants (5.5%). These participants will be excluded from the Jidong cohort study, and the remaining participants will be followed up. (2) Of the 320 participants with cognitive impairment, there was a significantly higher prevalence of illiteracy than other education levels (35.9%, P < 0.05). Age, arterial hypertension, alcohol consumption, and passive smoking differed significantly between the cognitive impairment and healthy groups (P < 0.05). Multivariate logistic regression models showed that age (odds ratio [OR] = 1.059, 95% confidence interval [CI]: 1.044-1.074) and arterial hypertension (OR = 1.665, 95% CI: 1.143-2.427) were risk factors for mild cognitive impairment. With the increase of educational level (illiteracy, primary school, junior high school, high school, university, and above), cognitive impairment gradually decreased (OR < 1, P < 0.05). (3) This cohort study has initially screened for several risk factors for cognitive impairment at baseline, and subsequent prospective data will further describe, validate, and evaluate the effects of these risk factors on cognitive impairment and dementia. These results can provide clinical evidence for the early prevention of cognitive impairment and dementia. The study was approved by the Ethics Committee of Kailuan General Hospital of Tangshan City and the Medical Ethics Committee, Staff Hospital, Jidong Oilfield Branch, China National Petroleum Corporation on July 12, 2013 (approval No. 2013 YILUNZI 1).

Project description:BackgroundCurrent demographic trends point towards an aging society entailing increasing occurrence and burden of neurodegenerative diseases. In this context, understanding physiological aging and its turning point into neurodegeneration is essential for the development of possible biomarkers and future therapeutics of brain disease.MethodsThe SENIOR study represents a longitudinal, observational study including cognitively healthy elderlies aged between 50 and 70?years old at the time of inclusion, being followed annually over 10?years. Our multimodal protocol includes structural, diffusion, functional, and sodium magnetic resonance imaging (MRI) at 3?T and 7?T, positron emission tomography (PET), blood samples, genetics, audiometry, and neuropsychological and neurological examinations as well as assessment of neuronal risk factors.ResultsOne hundred forty-two participants (50% females) were enrolled in the SENIOR cohort with a mean age of 60 (SD 6.3) years at baseline. Baseline results with multiple regression analyses reveal that cerebral white matter lesions can be predicted by cardiovascular and cognitive risk factors and age. Cardiovascular risk factors were strongly associated with juxtacortical and periventricular lesions. Intra-subject across-test variability as a measure of neuropsychological test performance and possible cognitive marker predicts white matter volume and is significantly associated with risk profile. Division of the cohort into subjects with a higher and lower risk profile shows significant differences in intra-subject across-test variability and volumes as well as cortical thickness of brain regions of the temporal lobe. There is no difference between the lower- and higher-risk groups in amyloid load using PET data from a subset of 81 subjects.ConclusionsWe here describe the study protocol and baseline findings of the SENIOR observational study which aim is the establishment of integrated, multiparametric maps of normal aging and the identification of early biomarkers for neurodegeneration. We show that intra-subject across-test variability as a marker of neuropsychological test performance as well as age, gender, and combined risk factors influence neuronal decline as represented by decrease in brain volume, cortical thickness, and increase in white matter lesions. Baseline findings will be used as underlying basis for the further implications of aging and neuronal degeneration as well as examination of brain aging under different aspects of brain pathology versus physiological aging.

Project description:BackgroundChronic kidney disease is common and is associated with cardiovascular disease, cerebrovascular disease, and cognitive function, although the nature of this relationship remains uncertain.Study designCross-sectional cohort using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT).Setting & participantsParticipants 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).PredictorsUrine albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR).OutcomesCognitive 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.ResultsOf 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.LimitationsCross-sectional only, no patients with diabetes were included.ConclusionsIn 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.

Project description:Background & hypothesisCognitive impairment is common in patients being evaluated for a kidney transplant (KT). The association between pretransplant cognitive function and posttransplant outcomes is unclear.Study designWe performed a prospective cohort study to assess the association between pretransplant cognitive function and clinically relevant posttransplant outcomes.Setting and populationIn this single center study, participants from the transplant clinic were evaluated during their pretransplant clinic visits and followed prospectively.OutcomesOur primary outcome measure was allograft function. Secondary outcomes were length of hospitalization for KT, hospital readmission within 30 and 90 days, graft loss, graft rejection within 90 days and 1 year, and mortality.Analytic approachWe measured cognitive function with the Montreal Cognitive Assessment (MoCA) test. We assessed the association of pretransplant MoCA score with posttransplant outcomes; we used linear mixed effects models to assess the association with the change in estimated glomerular filtration rate, Poisson regression for length of hospitalization, Cox proportional hazard model for graft loss and mortality, and a logistic regression model for readmission and rejection.ResultsWe followed 501 participants for 2.7 ± 1.5 years. The mean age of the patients was 53 ± 14 years and the mean pretransplant MoCA score was 25 ± 3. Lower pretransplant MoCA scores did not adversely affect the primary outcome of allograft function or the secondary outcomes. Although higher MoCA scores predicted a higher decline in graft function (β = -0.28, 95% CI: -0.55 to -0.01, P = 0.04), the effect was small and not clinically significant. Older age was associated with longer hospitalization, lower likelihood of rejection, and higher mortality. Deceased donor KT (vs living donor KT) was associated with longer hospitalization but better graft function. Longer time receiving dialysis before KT was associated with longer hospitalization. A history of diabetes mellitus was associated with higher mortality.LimitationsSingle center study limiting generalizability.ConclusionsPretransplant MoCA scores were not associated with the primary outcome of allograft function or the secondary outcomes.

Project description: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.

Dataset Information

The Brain in Kidney Disease (BRINK) Cohort Study: Design and Baseline Cognitive Function.

Publications

The Brain in Kidney Disease (BRINK) Cohort Study: Design and Baseline Cognitive Function.

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