Brain, Stroke and Kidney

K. Toyoda

• Publisher: S. Karger
• Year: 2013
• ISBN:
  9783318023527
• Topic: Medicina
• Subtopic: Nefrologia

Chronic kidney disease (CKD) is an established risk factor for cardiovascular diseases. Stroke, on the other hand, is not only a major player in cardiovascular disease, but it also has strong two-way relationships with CKD. Moreover, subclinical cerebral abnormalities are also associated with CKD. But despite all these connections, the cerebro-renal interaction has so far not received much attention. This book includes easily understandable reviews on brain, stroke and kidney by both experts in nephrology and neurology. Examined are underlying concepts for cerebro-renal interaction, risk of clinical and subclinical brain damage in CKD patients, primary prevention and acute/chronic management for stroke patients with CKD and end-stage kidney disease.This book promotes not only further understanding and a multidisciplinary collaboration between nephrologists and neurologists, but it is also of interest for neurosurgeons and cardiologists.

Risk of Clinical and Subclinical Brain Damage in Kidney Disease

Toyoda K (ed): Brain, Stroke and Kidney.
Contrib Nephrol. Basel, Karger, 2013, vol 179, pp 42-57 ( DOI: 10.1159/000346722 )

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Kidney Disease and Cognitive Function

Merrill F. Elias^a · Gregory A. Dore^b · Adam Davey^c

^aDepartment of Psychology and Graduate School of Biomedical Sciences and ^bDepartment of Psychology, The University of Maine, Orono, Me., and ^cDepartment of Public Health, Temple University, Philadelphia, Pa., USA

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Abstract

We provide a brief review of research on chronic kidney disease and cognitive performance, including dementia. We touch briefly on the literature relating end-stage-renal disease to cognitive function, but focus on studies of modest and moderate forms of chronic kidney disease (CKD) that precede dialysis and transplantation. We summarize previous reviews dealing with case control studies of patients but more fully examine community-based studies with large samples and necessary controls for demographic risk factors, cardiovascular variables, and other confounds such as depression. In addition we suggest potential biological and social-psychological mediators between CKD and cognition. Studies follow in two categories of design: (1) cross-sectional studies, and (2) longitudinal studies. In each, CKD is related to a wide range of deficits in cognitive functioning including verbal and visual memory and organization, and components of executive functioning and fluid intellect. In general, prior to the need to treat with hemodialysis (HD) or kidney transplant (KT), magnitude of effect with relation to CKD and function are small or modest in persons free from acute stroke and dementia. However, HD and KT can result in major impairment. We discuss needed controls, the greater demand on controls after the start of HD and KT, and suggest that mechanisms intervening relations between hypertension, or diabetes, and cognitive performance may be similar to those intervening between hypertension and cognitive performance and the hypertension and diabetes literature on cognition provides a good model for the study of early stage kidney disease and cognitive ability. We posit that the mechanisms linking CKD and cognition may be similar to those linking hypertension or diabetes to cognition. We identify the need for more studies with multiple cognitive test batteries, measures of every-day cognitive abilities relevant to patient understanding of the disease and treatments, and more studies with prevalent and incident dementia outcomes. Descriptors: kidney disease, chronic kidney disease, cognitive function, dementia and cardiovascular risk factors.

Copyright © 2013 S. Karger AG, Basel

Table 1. Common predictor variables in studies of renal disease and cognitive performance

Predictor	Metric or type of measurement	Type of variable
Uremic patient^1 vs. controls eGFR^2 Serum creatinine (sCR) Stage of kidney disease^3	diagnostic criteria ml/min/1.73 m^2 body surface mg/dl or umol/l standard diagnostic criteria	categorical categorical^4 or continuous continuous^5 categorical
^1Uremia defined as the accumulation of urinary waste products in the urine or the constellation of signs and symptoms indicating kidney disease or failure. ^2eGFR can be estimated via different formulae: modification of diet in renal disease (MDRD) study equation; chronic kidney disease epidemiology collaboration (CKD-EPI) equation; Mayo Clinic Quadratic equation. ^3See reference 5 for definitions and criteria. ^4Studies often use eGFR ≥60 (ml/min/1.73 m^2) versus <60, or, for example, normal (≥90); mildly decreased (60 to 89); moderate CKD (30-59), severe CKD (15 to 29) and kidney failure (<15), or clinical criteria, tertiles, quartiles, quintiles etc. ^5Continuously distributed such as eGFR in units (ml/min/1.73 m^2) or sCR in units (1 mg/dl) expressed as 1/sCR due to skew [e.g. 26].

A new case of dementia occurs every 4 seconds worldwide, which is equivalent to 7.7 million cases each year, and mild cognitive impairment is even more prevalent [1]. Chronic kidney disease (CKD) is a risk factor (RF) for dementia and cognitive decline [2, 3–5]. Cognitive impairment detracts from quality of life and is a risk factor for dialysis-related mortality [6]. In this brief review we summarize the literature on CKD in relation to cognitive function, discuss intervening mechanisms, and comment on some methodological issues, but refer the reader to other reviews of the many studies comparing treatments such as hemodialysis (HD), peritoneal dialysis (PD) and transplantation. We emphasize a pretreatment stage of CKD, but include studies examining modest to severe CKD.

Renal Functioning Predictors of Cognitive Function

Renal disease is well-defined in previous reviews [2, 3, 5, 7]. Table 1 summarizes commonly used predictor variables in cognitive studies and the measurement metrics used to define them. Common predictors are estimated glomerular filtration rate (eGFR), serum creatinine (sCR) and far less commonly stages of renal disease [2] involving measures such a proteinuria, biopsy or structural imaging.

Cognitive Outcomes in Renal Studies

A previous review provides a list of tests commonly used in the renal literature [3] and other reviews illustrate how multiple tests should be used where the goal is to infer the locus of brain impairment from one or more specific cognitive deficits [8, 9]. Studies designed to examine which abilities do and do not relate to a disease must examine a wide range of different abilities [8, 9]. Definitions of terms used in the psychometric literature are given in table 2. Outcome variables can be dichotomous (i.e. dementia, impairment, deficit), ordinal categories of performance level, or continuously distributed test scores representing performance level. We use the term cognitive impairment only if this cognitive status has been established by clinical criteria, i.e. neuropsychological (NP) evaluation and/or normative data. The term deficit is used as a comparative term indicating a lower average level of performance relative to a reference group or groups. The term decline is only used for longitudinal change in performance.

Overview: End-Stage Renal Disease and Treatment

We refer the reader to previous reviews [2, 3, 5] for a summary of this literature. However, it is important to note that an estimated 70% of HD patients over age 55 exhibit moderate-to-severe cognitive impairment [5] with a similar prevalence for PD patients [10]. Griva et al. [6] reported that two-thirds of a community-dwelling sample of 145 PD, home dialysis and in-center HD patients in London, UK, suffered from what the authors defined as mild or moderate cognitive impairment: 1.00-1.99 and 2-2.99 SD below the mean, respectively. We agree with Murray and Knopman [5] that performance 2.00 SD below the mean (2% of the population fall here) is not moderate, but is reflective of clinically significant cognitive dysfunction. Comprehensive reviews of this literature indicate that HD, PD and transplantation are associated with wide ranging deficits in attention, memory, speed of performance, and components of executive functioning (EF) [5], although it is clear that adverse cognitive outcomes are attenuated when cognitive testing is timed properly in relation to dialysis treatment [2].

There have been few studies of practical everyday cognitive tasks and kidney disease. Numeracy skills are critical to advance planning necessary to comply with treatment regimens and disease understanding [11]. Numeracy...