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      Kidney Disease and Cognitive Function: African American-Diabetes Heart Study MIND

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          Abstract

          Aims: Albuminuria and reduced estimated glomerular filtration rate (eGFR) are linked with poorer cognitive performance in European-ancestry populations with advanced nephropathy; relationships in African Americans (AAs) with type 2 diabetes (T2D) are less clear. Tests of cognitive performance, urine albumin:creatinine ratio (UACR), and CKD-EPI eGFR were performed in unrelated AAs with T2D to determine relationships. Methods: Cross-sectional analysis of 263 unrelated AAs with T2D recruited in the African American-Diabetes Heart Study (AA-DHS) MIND. Global cognitive function (mini-mental state exam [3MSE] and Montreal Cognitive Assessment [MoCA]), memory (Rey Auditory Verbal Learning Test [RAVLT]), executive function (Stroop, verbal fluency for animals, and Digit Symbol Copy [DSC]), UACR, and eGFR were determined. Relationships between cognitive tests and renal parameters were assessed using multivariate models, adjusted for age, gender, body mass index, hemoglobin A1c, level of education, hypertension, and LDL cholesterol. Results: Participants had a mean ± SD age of 60.2 ± 9.7 years, 62.7% were female, T2D duration was 14.3 ± 8.9 years, eGFR 86.0 ± 23.2 ml/min/1.73 m<sup>2</sup>, and UACR 155.8 ± 542.1 (median 8.1) mg/g. In adjusted models, higher UACR was associated with worse 3MSE (p = 0.014), MoCA (p = 0.0089), DSC (p = 0.0004), Stroop performance time (p = 0.003), Stroop errors (p = 0.032), and Stroop interference (p = 0.026). Higher eGFR was associated with better performance on DSC (p = 0.0071). Conclusions: In AAs with T2D, albuminuria and eGFR were associated with cognitive function, even in mild kidney disease. These data stress the need for interventions to prevent cognitive decline well before the late stages of kidney disease.

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          Most cited references 16

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          MoCA, ACE-R, and MMSE versus the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards Neuropsychological Battery after TIA and stroke.

          The Montreal Cognitive Assessment (MoCA) and Addenbrooke's Cognitive Examination-Revised (ACE-R) are proposed as short cognitive tests for use after stroke, but there are few published validations against a neuropsychological battery. We studied the relationship between MoCA, ACE-R, Mini-Mental State Examination (MMSE) and mild cognitive impairment (MCI) in patients with cerebrovascular disease and mild cognitive impairment (MCI). One hundred consecutive non-institutionalized patients had the MMSE, MoCA, ACE-R, and National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards Neuropsychological Battery ≥ 1 year after transient ischemic attack or stroke in a population-based study. MCI was diagnosed using modified Petersen criteria in which subjective cognitive complaint is not required (equivalent to cognitive impairment-no dementia) and subtyped by number and type of cognitive domains affected. Among 91 nondemented subjects completing neuropsychological testing (mean/SD age, 73.4/11.6 years; 44% female; 56% stroke), 39 (42%) had MCI (amnestic multiple domain=10, nonamnestic multiple domain=9, nonamnestic single domain=19, amnestic single domain=1). Sensitivity and specificity for MCI were optimal with MoCA 70% at a cutoff of <29, mainly due to relative insensitivity to single-domain impairment. The MoCA and ACE-R had good sensitivity and specificity for MCI defined using the Neurological Disorders and Stroke-Canadian Stroke Network Vascular Cognitive Impairment Battery ≥1 year after transient ischemic attack and stroke, whereas the MMSE showed a ceiling effect. However, optimal cutoffs will depend on use for screening (high sensitivity) or diagnosis (high specificity). Lack of timed measures of processing speed may explain the relative insensitivity of the MoCA and ACE-R to single nonmemory domain impairment.
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            Stroop interference: aging effects assessed with the Stroop Color-Word Test.

            A large, cross-sectional aging investigation of performance on the Stroop Color-Word Test (SCWT) was carried out. Subjects were 247 volunteers, ages 20-80 in seven age levels. Although all subjects thought themselves to be normal and healthy, a post hoc division could be made on the basis of biological life events (BLE). BLE are mild biological or environmental factors, such as repeated experiences of general anesthesia, that can hamper optimal brain functioning. Apart from the anticipated age effects, performance was poorer in subjects who had experienced one or more BLE: The slowing due to BLE was comparable to the effect of age, especially on the task involving language interference in color-naming. Education had a significant effect on performance: More highly educated subjects performed better than less educated subjects. No sex differences were observed. These findings replicate observations made with other tests in parallel studies. They are also in line with several other studies reporting interactions between the effects of aging and physical fitness. This study questions some of the validity of cognitive aging research, as our data suggest that screening for BLE as age-extrinsic factors in nondiseased subjects can reduce many of the performance deficits usually ascribed to aging per se.
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              Uremic encephalopathy and other brain disorders associated with renal failure.

              Kidney failure is one of the leading causes of disability and death and one of the most disabling features of kidney failure and dialysis is encephalopathy. This is probably caused by the accumulation of uremic toxins. Other important causes are related to the underlying disorders that cause kidney failure, particularly hypertension. The clinical manifestations of uremic encephalopathy include mild confusional states to deep coma, often with associated movement disorders, such as asterixis. Most nephrologists consider cognitive impairment to be a major indication for the initiation of renal replacement therapy with dialysis with or without subsequent transplantation. Sleep disorders, including Ekbom's syndrome (restless legs syndrome) are also common in patients with kidney failure. Renal replacement therapies are also associated with particular neurologic complications including acute dialysis encephalopathy and chronic dialysis encephalopathy, formerly known as dialysis dementia. The treatments and prevention of each are discussed. © Thieme Medical Publishers.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2014
                October 2014
                10 October 2014
                : 40
                : 3
                : 200-207
                Affiliations
                aDepartment of Biochemistry, bCenter for Genomics and Personalized Medicine Research/Center for Diabetes Research, cDepartment of Internal Medicine-Section on Gerontology and Geriatric Medicine, dDepartment of Radiology, ePublic Health Sciences, and fDepartment of Internal Medicine-Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, N.C., USA
                Author notes
                *Barry I. Freedman, MD, Section on Nephrology; Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1053 (USA), E-Mail bfreedma@wakehealth.edu
                Article
                367669 PMC4216628 Am J Nephrol 2014;40:200-207
                10.1159/000367669
                PMC4216628
                25323981
                © 2014 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Tables: 4, Pages: 8
                Categories
                Original Report: Laboratory Investigation

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