1

ASSESSMENT OF COGNITIVE FUNCTION IN PATIENTS

WITH STAGE 3 TO 5 CHRONIC KIDNEY DISEASE AT THE

UNIVERSITY COLLEGE HOSPITAL, IBADAN.

BY

UDUAK E. WILLIAMS MB, B.Ch (CALABAR) 1999

A DISSERTATION SUBMITTED TO THE NATIONAL

POSTGRADUATE MEDICAL COLLEGE OF NIGERIA IN

PARTIAL FULFILMENT OF THE AWARD OF THE

FELLOWSHIP OF THE COLLEGE OF PHYSICIANS

(IN THE SUBSPECIALTY OF NEUROLOGY).

NOVEMBER 2010

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DECLARATION

I declare that this dissertation is an original work by me. It has not been presented to

any other college for a fellowship award nor has it been submitted elsewhere for

publication.

Signature……………………….........................................

Name…………………………….........................................

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CERTIFICATION

The study reported in this dissertation was done by this candidate Dr Uduak E. Williams

under my supervision. I have also supervised the writing of the dissertation to my

satisfaction and authorized the submission of the work for the Fellowship Examination

in the Faculty of Internal Medicine.

Supervisor

Signature.....................................................................

Name of supervisor......................................................

Status of supervisor......................................................

Date..............................................................................

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ATTESTATION

I certify that the work reported in this dissertation was carried out by Dr Uduak E.

Williams in the Department of Medicine, University College Hospital, Ibadan and under

the supervision of Professor Adesola Ogunniyi.

Address...........................................................................................................

Name...............................................................................................................

Signature.........................................................................................................

Designation.....................................................................................................

Date................................................................................................................

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DEDICATION

This dissertation is dedicated foremost to Him who was, and is, and is to come. And to

my lovely ladies- Honey girl and Jessica for their inspiring love.

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ACKNOWLEDGEMENT

I will like to acknowledge my supervisor and mentor, Professor Adesola Ogunniyi for

painstakingly taking me through this dissertation and for giving me the chance to hone

my clinical skills in Neurology.

Drs OSA Oluwole and MO Owolabi deserve special thanks for their unquantifiable

contribution to my training as a Neurologist. I will indeed eternally remain grateful to

them.

My special thanks to the consultant staff and residents of the University College Hospital

(UCH) and the neurology unit for contributing to making me a better physician

Drs Adedokun and Ameh deserve special mention for their contributions as medical

statisticians to this work.

The University of Calabar Teaching Hospital (UCTH) paid my salary and other

allowances during the period of my training and are hereby heartily commended. My

immediate bosses Dr(Mrs) Philip-Ephraim and Dr Sidney Oparah, and other consultant

staff of Internal Medicine department UCTH including Prof C. Odigwe, Drs V. Ansa, O.

Essien, E. Peters, and R. Agbulu encouraged me all the way during this training. I am

grateful to all of them. I am indebted to Drs Effa, Enang, Akpan, Odudu-Umoh, Umoh,

Otu, Ekanem, Ezunu, and Onaga for their friendship. Theirs is an uncommon assistance

and unyielding encouragement throughout the duration of this work.

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Let me also appreciate my siblings Eno, Maggi, Edem, Felicia, Maria and Rosa for all

their prayers! Many thanks to you all!

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TABLE OF CONTENTS

Title page … … … … … … … … … … … … i

Declaration … … … … … … … … … … … ii

Certification … … … … … … … … … … … iii

Attestation… … … … … … … … … … … … iv

Dedication … … … … … … … … … … … … v

Acknowledgement… … … … … … … … … … … vi

Table of contents… … … … … … … … … … … vii

List of Tables… … … … … … … … … … … x

List of Figures… … … … … … … … … … … xi

Key to abbreviations… … … … … … … … … … xii

ABSTRACT … … … … … … … … … … … … xiii

CHAPTER ONE: INTRODUCTION… … … … … … … … 1

CHAPTER TWO: AIMS AND OBJECTIVES… … … … … … … 4

CHAPTER THREE: LITERATURE REVIEW… … … … … … … 5

CHAPTER FOUR: MATERIALS AND METHODS… … … … … … … 23

CHAPTER FIVE: RESULTS… … … … … … … … … 30

CHAPTER SIX: DISCUSSION … … … … … … … … … 56

CHAPTER SEVEN: CONCLUSION, LIMITATIONS AND

RECOMMENDATION… … … … … … … 64

REFERENCES … … … … … … … … … … … 66

APPENDIX 1: CONSENT DOCUMENT(ENGLISH)… … … … … … 76

APPENDIX 2: CONSENT DOCUMENT (YORUBA)… … … … … … 77

APPENDIX 3: QUESTIONAIRE … … … … … … … … … 78

9

APPENDIX 4: TRAIL MARKING TEST A… … … … … … … … 80

APPENDIX 5: TRAIL MARKING TEST B… … … … … … … … 81

APPENDIX 6: COMMUNITY SCREENING INSTRUMENT FOR DEMENTIA… … … 82

APPENDIX 7: ETHICAL APPROVAL CERTIFICATE… … … … … … 91

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LIST OF TABLES

Table 1: Socio-demographic characteristics of subjects and controls… …. 31

Table 2: Presence of cognitive impairment among CKD patients and controls

using CSID…. …. …. …. …. …. …. … …. 33

Table 3: Presence of cognitive impairment among CKD patients and controls

using TMTA… … … … … … … … ... 41

Table 4: Presence of cognitive impairment among CKD patients and controls

using TMTB… … … … … … … … … 43

Table 5: Correlation of cognitive in CKD patients with biochemical parameters,

packed Cell volume and blood pressure based on CSID performance 45

Table 6: Correlation of cognitive in CKD patients with biochemical parameters,

packed Cell volume and blood pressure based on TMTA performance 47

Table 7: Correlation of cognitive in CKD patients with biochemical parameters,

packed Cell volume and blood pressure based on TMTB performance 49

Table 8: Multivariate logistic regression analysis of accurate predictors of

cognitive Impairment using CSID… … … … … … 51

Table 9: Comparism of the mean CSID performance between controls and CKD

Patients… … … … … … … … … … 53

Table 10: Comparism of the mean time taken to complete TMTA and TMTB among

the controls and CKD patients… … … … … … .. 55

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LIST OF FIGURES

Figure 1: Percentage distribution of the CKD patients by the disease stage… … 35

Figure 2: Cumulative dialysis sessions undertaken by CKD patients… … … 37

Figure 3: Error bar showing the total CSID score of controls, CKD patients and

the subjects in the pre-test population… … … … … … 39

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LIST OF ABREVIATIONS

CGF - Cockcroft-Gault formula

CNS - Central nervous system

CrCl - Creatinine clearance

CSID - Community screening instrument for dementia

CVLT - California verbal learning test

EEG - Electroencephalogram

eGFR - Estimated glomerular filtration rate

ERP - Event related potential

ESRD - End-stage renal disease

FePsy - Iron-psychology test battery

GFR - Glomerular filtration rate

IQ - Intelligence quotient

K/DOQI - Kidney disease outcome quality initiative

MDRD - Modification of diet in renal disease

MMSE - Mini-mental state examination

NHANES 111 - 3rd National health and nutrition examination survey

NKF - National Kidney foundation

PCV - Packed cell volume

SDLT - Serial digital learning test

SDST - Symbol digit subtraction test

SRTT - Simple reaction test time

3MS - Modified Mini-mental scale examination

6CIT - 6-Item cognitive impairment test

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SUMMARY

Background: Cognitive impairment has been reported in chronic kidney disease (CKD).

This has a negative effect on quality of life. This study was prompted by the paucity of

literature on cognitive impairment in Nigerians and indeed Africans with CKD.

Objectives: To determine the frequency, pattern and predictors of cognitive

impairment in patients with stages 3 to 5 CKD.

Method: Cognitive function was assessed in the CKD patients and controls using

community screening instrument for dementia (CSID), trail marking test A (TMTA) and

trail marking test B (TMTB).

Results: The number of CKD patients with cognitive impairment using CSID compared

with controls was 41(51.9%) and 2(2.5%) (X2=48.59; p=<0.001); on TMTA it was

42(53.2%) and 0(0%) (X2=57.21;p=<0.001); and on TMTB it was 22(40%) and

0(0%) (X2=35.26; p=<0.001) (X2=35.26; p=<0.001).

The odds of having cognitive impairment increased in the presence of CKD when

assessed using CSID (OR=2.026; CI=1.607-2.555); TMTA (OR=3.13; CI=2.40-4.09)

and TMTB (OR=3.22; CI=2.42-4.25). The best predictor of cognitive impairment was

the estimated glomerular filtration rate (β=0.378; CI=-1.560-0.208).

CKD patients performed poorer on tests of executive function TMTA ( t=67.848;

p=<0.001) and TMTB (t=27.30; p=<0.001). But CSID showed significantly lower

scores for CKD patients on naming (t=13.100; p=<0.001); fluency (t=9.760;

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p=<0.001); attention/calculation ( t=3.098; p=<0.001); orientation in place (t=4.048;

p=<0.001); immediate recall (t=8.497;p=<0.001) and praxis (t=10.504; p=<0.001).

Conclusion: The result shows that there is a high prevalence of cognitive impairment

among CKD patients. The cognitive domain impaired includes executive function,

language, attention, calculation, orientation in place, immediate recall and praxis.

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CHAPTER ONE

INTRODUCTION

Chronic kidney disease (CKD) is a growing public health problem,1,2,3 with incidence

rising in all age groups.1 There is also an increase in prevalence globally.4,5,6 Although

the exact prevalence is not known in Nigeria, it is reported to account for 1-8% of

hospital admissions,3,7,8 and it is an important cause of morbidity and mortality.9 CKD

often go unrecognised for years, until late in the course of the disease.10

Individuals with CKD defined either as Glomerular Filtration Rate (GFR) less than 60ml

per minute per 1.73m2 body surface area or kidney damage for three or more

months,11-14 at all stages are at a higher risk of developing neurocognitive

impairment.1,3,15 This impaired cognitive function greatly affects their quality of life3.

Cognitive impairment is found even in young patients with mild CKD.12Cognitive

function is viewed in terms of information processing and the adaptive behaviour that

depends on it, with its sphere including memory, attention, calculation, language,

executive function, higher sensory perception, visual perception and praxis. 16

Cognitive impairment is defined as a deficit involving at least two areas of cognition1

including aspects of memory, executive functioning, attention, perceptual motor abilities

and language. The high burden of cognitive impairment in CKD patients has only been

recently recognised.17, 18 Murray observed that up to 70% of haemodialysis patients

aged 55years and above have moderate to severe cognitive impairment.19

16

Early diagnosis and prompt treatment to retard the progress of cognitive decline in

patients with CKD is very important as poor cognitive function has been associated with

increased risk of death in dialysis patients.20 It is a key determinant of quality of life

since patient’s decision making and adherence to both pharmacological and non-

pharmacological management principles depend on a sound cognitive state.21

The exact pathophysiologic mechanism for cognitive decline in patients with CKD is not

yet determined.1,11,22 Several factors have been linked with the development of

cognitive impairment in the setting of CKD including elevated cytokines, serum lipids21

and clinical parameters such as asterixis, hypertension, anaemia, nausea, and

vomiting.15 Electrolyte derangement and uremic acidosis are also thought to play an

important role. A positive correlation has also been established between cognitive

impairment in CKD and serum creatinine, urea, uric acid and serum calcium levels.15

Tests for neurocognitive function can be broadly classified into neurophysiological and

neuropsychological tests.1, 23 Examples of neuropsychological tests are Mini-Mental

State Examination (MMSE), Modified Mini-Mental State Examination (3MS), Community

Screening Instrument for Dementia (CSID), and Trail Marking Test A& B (TMTA &

TMTB). Electroencephalogram (EEG), Cognitive evoked potential and Sensory evoked

potential are examples of neurophysiologic tests.

The high incidence of cognitive impairment in CKD is largely unrecognised17 thus,

increasing the burden on care givers. It results in greater utilisation of health resources,

more frequent hospitalisation, increased number of days spent in the hospital, and

17

difficulty obtaining consent from patients for necessary treatment procedures.22,24

People with cognitive impairment are at a greater risk of employment problems and this

could compromise money available for treatment. Cognitive impairment in CKD

therefore mitigates against improved quality of life which is the main focus in the

management of these patients.20,25, 26

To address the above mentioned challenges, there is the need to assess neurocognitive

function in CKD patients with a view to determining the pattern of cognitive decline, the

biochemical and clinical correlates, and other possible associations. Although, cognitive

function in CKD has been widely studied in the western world, few studies are available

in Nigeria and indeed Africa.15 It is in a bid to address this information gap that this

cross-specialty study was undertaken.

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CHAPTER TWO

AIMS AND OBJECTIVES

GENERAL:

To determine the frequency, pattern and predictors of cognitive impairment in

patients with stages 3 to 5 CKD at the University College Hospital, Ibadan.

SPECIFIC:

1. To ascertain the correlation between cognitive function and biochemical

parameters such as serum urea, creatinine, sodium, potassium, phosphate,

calcium, and uric acid in patients with CKD.

2. To determine the correlation between level of haemoglobin and cognitive

function in CKD patients.

3. To determine the correlation between the cognitive scores and estimated

Glomerular Filtration Rate.

4. To determine the relationship between blood pressure and cognitive function in

CKD patients.

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CHAPTER THREE

LITERATURE REVIEW

3.1 Epidemiology

Chronic Kidney Disease (CKD) has been described by many as a growing public health

problem1,3,13,27 with evidence pointing to an increasing incidence and prevalence

worldwide.28,29 It affects about 6.2million people aged 12 years and above in the United

States2 .CKD is grossly under-diagnosed in Nigeria and indeed in the developed world.

According to Akinsolaet al, the hospital frequency ranged between 1.6 to 8% of hospital

admissions.5 Abioye-kuteyiet al reported a prevalence of 19.9% of undetected kidney

disease in a rural populace in Nigeria.30

CKD affects all races equally, but end-stage renal disease (ESRD) is four times more

prevalent in blacks than whites in the United States1. CKD is found in persons of all

ages, but higher incidence rates occur in patients 65 years and above. 31-33 A lower

average age has been reported among Nigerians.5

There is a high incidence of cognitive impairment among patients with chronic renal

impairment.1,15,23,31 Murray et al24 observed in their study of 338 haemodialysis patients,

that 37.0% had severe cognitive impairment which was more than three times the 5-

10% estimated prevalence of dementia in US population-based studies. Sehgalet al

reported a prevalence of 22% of mild mental impairment among haemodialysis

patients.34 Cognitive function is a major determinant of quality of life and outcome of

20

treatment.1Ogunrinetal at Benin15 studied sixty non-dialysed patients with clinical and

biochemical evidence of chronic renal failure and sixty age-, sex-, and educational level-

matched controls. The patients with chronic renal disease had significantly poorer

memory scores compared to controls. The CKD patients also had retardation of

psychomotor speed, which indicates slow perceptual motor speed. Madanet al23 and

Kurellaet al22 have shown that decreased kidney function is associated with decreased

cognition. Greater emphasis in the management of CKD is placed on early detection and

improvement of patient’s quality of life.15Hailpernet al12 studied 4849 subjects under the

Third National Health and Nutrition Examination Survey (NHANES 111). They reported

that moderate CKD was significantly associated with poorer performance in visual

attention and learning /concentration.

Kurellaet al 20 concluded that, cognitive impairment in CKD is associated with a poorer

prognosis. They therefore advocated routine screening for cognitive impairment among

elderly patients with CKD in order to identify those at risk for associated adverse

outcomes.

3.2 Definition and Classification of CKD

The definition and classification of CKD is helpful in identifying affected patients, with

the possibility of early institution of effective therapy35. Guidelines proposed by the

National Kidney Foundation (NKF) of the United States through its Kidney Disease

Outcomes Quality Initiative (K/DOQI) program is the internationally accepted basis for

staging CKD.23 K/DOQI defines CKD as either kidney damage or a decreased renal

glomerular filtration rate (GFR) of <60 mL/min/1.73 m2 for 3 or more months.11,13,14, 37

CKD is staged into five stages as follows: 27,33,39, 41

21

Stage 1: Kidney damage with normal or increased GFR

(>90 ml/min/1.73 m2)

Stage 2: Mild reduction in GFR (60-89 ml/min/1.73 m2)

Stage 3: Moderate reduction in GFR (30-59 ml/min/1.73 m2)

Stage 4: Severe reduction in GFR (15-29 ml/min/1.73 m2)

Stage 5: Kidney failure (GFR <15 ml/min/1.73 m2 or dialysis).

This K/DOQI definition and the classification of CKD allow better communication and

intervention at the different stages of CKD,41 it also predicts the risk of comorbidity and

complications.6

The two formulae which have been validated and commonly used to estimate the GFR

for staging CKD, are the Cockcroft-Gault formula (CGF) and the Modification of Diet in

Renal Disease (MDRD) Study equation. CGF for estimating creatinine clearance (CrCl) is

recommended routinely as a simple means to provide a reliable approximation of

residual renal function in all patients with CKD. CGF is simple and easy to apply, and

has been found to reliably and validly predict creatinine clearance in healthy patients as

well as those with CKD,39 it is better than MDRD for estimating eGFR in advance renal

disease. (M) The Cockcroft-Gault formula is as follows 39, 40

CrCl (male) = ([140-age] X weight in kg)/(serum creatinine in mg/dl X 72)

CrCl (female) = ([140-age] X weight in kg)/(serum creatinine in mg/dl X 72)X

0.85

22

The MDRD is believed to be more useful in elderly patients, 41 and for the outpatient

setting.42It is important to note that Kurellaet al reported that eGFR results obtained

from using MDRD and those using CGF to be similar.22

3.3 Cognitive Function

The key areas of cognition are attention, memory, language, visuo-spatial skills and

frontal/executive functions.24, 16 Attention is the level of wakefulness, and has been

seen by Grabowski et al 43as “ orientation to and action upon selected sensory

perceptions and conjunctive operation”, when it is lost, patients becomes easily

distractible. Attention depends on an intact reticular activating system with its

projections to the reticular nucleus of the thalamus, and the frontal cortex where it is

related to working memory. 43

Memory involves the encoding, storage and retrieval of information. 43A defect in one or

more of these components of memory results in amnesia.43Memorycould be short term

or long term or immediate recall.43, 44The anatomic substrate for memory includes;

mesial temporal lobe for episodic memory, cerebellum and basal ganglia for motor

learning, and prefrontal cortex for working memory. 43The basal forebrain nuclei

produce acetylcholine which is the major neurotransmitter involved in memory, loss of

cholinergic function is a key feature of dementia.45

Language disturbance occurs in affectation of the dominant hemisphere.45 An acquired

defect in language comprehension or formulation is referred to as aphasia. 43The

anatomical substrate of language among others includes; Broca’s area in the inferior

23

gyrus which is responsible for speech formulation, and the Wernicke’s area in the

posterior aspect of the left superior temporal gyrus involved in speech comprehension.

43, 45

The parietal lobe in the right hemisphere controls visuo-spatial skills which are the

processes by which objects are arranged in space under visual guidance such as three-

dimensional constructions with blocks and drawings. 43, 45Apraxia is a disorder of skilled

movement in the absence of motor, sensory or cerebellar disorder. 43The cortical lesions

involving the left parietal lobe in right handed persons results in apraxia. 43

Executive function involves the processes concerned with decision making,

prioritization, planning and social response to the environment. It depends on the

functioning of the prefrontal cortex. 43Grabowski et al 43divided signs of its dysfunction

into negative and positive, with examples of the negative signs being lack of planning,

failure to complete task, deficient empathy and limited behaviour initiation; while the

positive signs would include; social disinhibition, perseveration, impulsiveness and

distractibility.

3.4 Cognitive Dysfunction

Cognitive impairment has been defined as a deficit in at least two aspects of cognitive

function1. This could involve a combination of changes in memory, executive function,

attention, perceptual motor skills and language. When activities of daily living are not

affected, cognitive impairment is said to be mild. Dementia on the other hand, affects

activities of daily living and behaviour.1, 46 This can also be defined with respect to the

24

assessment test used for assessing the cognitive performance.1 A cut-off score of less

than 80 is used when using the Modified Mini Mental Scale (3MS) and less than 24 with

Mini Mental State Examination (MMSE).1, 22 However, such tests showing educational

and cultural biases are not valid for use in predominantly illiterate populations.1

3.5 Cognitive Dysfunction in Chronic Kidney Disease

There is a growing interest in studying cognitive function in CKD because of its

detrimental effect on health-related quality of life measures.6 47Etgenet al 3 enrolled a

total of 3679 participants in the Intervention Project on Cerebrovascular Disease and

Dementia in the community-based cohort study, and observed an association between

moderate to severe impaired kidney function and incident cognitive impairment after

two years.

Kurellaet al 48 in their study of primarily white postmenopausal women who had

coronary artery disease and participated in the Heart Oestrogen/ Progestin Study,

observed that low eGFR significantly associated with impaired global cognitive function,

executive function, language, and memory. This observed association was independent

of residual effects of age and race and other cofounding variables. In studying cognitive

function in stage 3-4 CKD patients, Kurellaet al20 observed that they had worse

performance on tests of executive function and verbal memory compared with

published norms. In another study,31 poorer performance on TMTB and Modified Mini-

mental State Examination was also reported among stages 3 and 4 CKD patients when

compared with age and education matched published norms.

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In children with ESRD, Fannellet al49 demonstrated that the acquisition of new

information and problem solving processes are more likely to be affected than

previously learned materials such as factual material and vocabulary. In “the Health,

Aging, and Body composition study”, Kurellaet al 22 showed that change in cognitive

function vary directly over time with the severity of CKD. The Reasons for Geographic

and Racial Differences in Stroke (REGARDS) study50concluded that impaired kidney

function was associated with increased prevalence of cognitive impairment independent

of confounding factors.

Slickers et al51 studied twenty-nine children aged 7-19years, with an estimated

creatinine clearance of 4-89ml/min per 1.73m2 body surface area. They observed that

increased severity of CKD was associated with lower memory function and intelligence

quotient (IQ) scores. They further concluded that, increased disease severity, longer

duration of disease and younger age of onset of kidney disease potentially place

children with CKD at increased risk of neurocognitive deficits.

3.6 Mechanism and Risk Factors of Cognitive Impairment in CKD

The mechanism by which cognitive dysfunction occurs in CKD is not fully

understood.1,15,20,52, Though the pathophysiology is poorly understood, the public health

implications of this substantial burden are immediate.11This lack of proper

understanding of the risk factors for cognitive impairment has greatly affected the

availability of treatment for this group of patients1. However, traditional risk factors that

are associated with cognitive impairment in the general population such as age,

26

hypertension, diabetes, hyperlipidaemia,53depression54and high normal uric acid19 are

often prevalent in patients with CKD. These risk factors may cause subclinical damage

to the central nervous system (CNS).12 Cerebrovascular disease is believed to be a

stronger risk factor for cognitive impairment in CKD than Alzheimer’s disease.1Buchman

et al 55observed that a low eGFR at baseline was associated with a more rapid cognitive

decline.

Accumulation of solutes has also been implicated as a cause of cognitive impairment in

CKD, which may make it a potentially reversible cause.12This is in keeping with the

findings of Fennell etal49 who found improvement of cognitive function in CKD patients

one year after renal transplant.Madero et al1 summarized by grouping risk factors for

cognitive impairment into vascular, non-vascular and procedure related factors.

Examples of the vascular risk factors include hypertension and hypercholesterolemia,

while the non-vascular risk factors include anaemia, hyperparathyroidism, poly-

pharmacy, and sleep disturbances. The procedure related risk factors are

haemodialysis-related hypotension, microembolization, and cerebral oedema. Murray et

al 22believe these key changes are that of acute intravascular volume loss and fluid

shifts that occur during dialysis. This then induces cerebral oedema, and decreased

intracerebral blood pressure, blood velocity, and cerebral perfusion.

3.7 Predictors of Cognitive Dysfunction in Patients with CKD

Several biochemical abnormalities have been used to explain the cognitive dysfunction

in CKD patients; these include intracellular and extracellular cation and anion changes.56

27

Ogunrinet al15 observed that creatinine level greater than 9mg/dl and increased urea

adversely affected the verbal memory performance of patients with CKD. This

association was also reported by Munang etal39 and Seligeret al57. In terms of clinical

features, they also noted an association between asterixis, exertional dyspnoea,

hypertension, nausea/vomiting and cognitive impairment. Creatinine level was the most

potent predictor of cognitive dysfunction. Madanet al23 also reported a positive

correlation between cognitive function in CKD patients and serum urea, creatinine and

uric acid levels, but noted significant negative correlation with GFR, serum calcium, and

haemoglobin. Hailpernet al in the NHANES 111 study12 concluded that, “compared with

those with normal kidney function, those with moderate CKD were more likely to be

older; have higher systolic and diastolic BP; be hypertensive; have higher total serum

cholesterol; have higher blood urea nitrogen (BUN); body mass index, C-reactive

protein; and albumin-to-creatinine ratio; and have lower HDL. Those with moderate

CKD were less likely to be black and consume one or more alcoholic drinks per week”.

Tsivgouliset al53observed the association of higher diastolic blood Pressure cross-

sectionally and independently with cognitive impairment in stroke free individuals.

Kurellaet al in studying correlates and outcome of dementia, 20 noted that there was no

significant association between diagnosed dementia and smoking status, blood

pressure, cholesterol, parathyroid hormone, dialysis dose or aluminium concentration.

However, it must be pointed out that they diagnosed cognitive impairment based on

subjects’ medical records but not on formal cognitive function testing.

28

The place of anaemia in cognitive impairment has been highlighted by several scholars,

and treatment of anaemia results in improved cognitive function.58, 59,60

Serum uric acid has been suggested as a possible marker of cognitive decline and

dementia especially in the elderly.61Its role in age-related cognitive decline is still

controversial because of its antioxidant properties. Elevated levels have been associated

with an increased burden of cerebral ischemia.18,62It has been studied as a marker for

CKD.63Schretlenet al53 pointed out the fact that its level increases in diseases that often

lead to cognitive impairment. They observed in a study of 96 elderly adults that patients

with serum uric acid at the upper limit of normal were 2.7 to 5.9 times more likely to

score in the lowest quartile of the sample on measures of processing speed, verbal

memory, and working memory.

3.8 Assessment of Cognitive Dysfunction in CKD

Neuropsychological and neurophysiologic test instruments have been used in assessing

cognitive impairment.1There are no clearly stated guidelines on the ideal instrument or

frequency for assessing cognitive impairment in patients with chronic kidney

disease(CKD).64How often patients are assessed and what instruments will be used will

depend on the availability of both instruments and the skilled man-power to use

them.64Ogunrinet al15 used the Iron Psychology test which is a computer-based

instrument. Differences have been reported when comparing their use to the pencil and

paper version, but it is still said to be valid.15Madanetal23 believe that since prolongation

of the P3 latency is one of the earliest signs in CKD, the events related potential (ERP)

29

assessment may be a more sensitive and useful method for assessing cognitive

function. Hailpernet al12 used three computer-based tests -Simple Reaction Time Test

(SRTT), Symbol Digit Subtraction Test (SDST), and Serial Digit Learning Test (SDLT).

Moderate CKD was only associated with poor cognitive function in two of the three

tests: SDST and SDLT. It must be pointed out that these computer-based tests may not

be widely available in low income countries, and even where available, level of

computer literacy may affect results obtained.

3.9 Impact of Cognitive Impairment on Quality of Life in CKD

It has been reported that cognitive impairment in CKD worsens the prognosis in

patients1, 47 and also increases the burden on medical and non-medical care

givers.Tamuraet al 64opined that cognitive impairment may hinder adherence to the

complex regimens often prescribed to renal failure patients, increases the risk of

adverse events and impair informed decision making. Kurella et al20 observed that

cognitive impairment has been associated with an increased risk of death and dialysis

withdrawal, independent of a number of confounding factors. Sehgal et al21 reported

that cognitive impairment was associated with an increased number of hospital days

and greater staff time after the termination of a dialysis session. Gusseloo et al noted

the association of severe cognitive impairment with increased mortality in their study of

impact of mild cognitive impairment on survival in very elderly people.65Studies1,64, 66, 67,

have concluded that cognitive impairment leads to difficulty in adhering to dialysis

recommendations especially with respect to dietary modifications and medication

compliance. They therefore opined that, studies to elucidate methods of halting or

30

delaying cognitive decline in CKD is a very pertinent area of medical research. Cognitive

impairment in ESRD is seen as one of the challenges in achieving performance targets

in patients’ management. 64

Sehgal et al21 were of the opinion that severe cognitive impairment in patients with CKD

may impede their ability to comply with dialysis schedules, medications, and fluid and

dietary restrictions, and ultimately lead to increased cost for dialysis unit care and

hospitalization. Murray et al24and Tamura et al64think that most importantly, such

patients may lack adequate judgement to make decisions regarding initiating,

maintaining dialysis and pre-emptive vascular assess placement. In another study,

Murray et al17reported that, severe cognitive impairment or dementia among

haemodialysis patients is associated with an appropriately 2-fold increase risk of both

mortality and dialysis withdrawal.

3.10 The Screening Instruments

There are no studies which have validated the best instruments for cognitive function

screening or a clinical diagnosis of dementia among CKD patients.64 Instruments used

will depend on the age, educational level and English fluency of the patients, as these

will influence their performance. 64The community screening instrument for dementia

(CSID) was developed by the Indianapolis-Ibadan dementia project group.68,69 It places

emphasis on making each item harmonious with the local language and culture.68 The

instrument is structured to assess the cognitive function of the participant and also

interview a close relative (informant) evaluating the daily functioning of the participant.

Initial studies at participant’s location are usually done to determine normative values

31

and optimum cut-off scores.68 As a neuropsychological test, it has been validated at the

University College Hospital Ibadan, and in communities for the Ibadan-Indianapolis

Dementia Project, it is said to have a sensitivity of 87% and specificity of 83%.68 The

CSID was designed specifically for use in non-literate and literate populations;

satisfactory performance has been reported in several populations.68 The adaptation of

its items to local language and culture, making it one of the most suitable instruments

in our African setting.68

The Trail Making Test A (TMTA) and Trail Making Test B (TMTB) are well-established

tests sensitive to impairment in multiple cognitive domains,70,71,72 The original form was

the Tailor number series consisting of numbers 1-50. It was later reviewed as part of

the Army Individual Test of General Ability and was given the name Trail Making Test.

It consists of two parts A and B, with emphasis placed on speed. The object of part A is

for the subject to connect encircled numbers from 1 to 25 randomly spread across a

sheet of paper beginning with 1 and ending with 25, in as little time as possible. Part B

is more complex than A because it requires the subject to connect numbers and letters

in an alternating pattern (1-A-2-B-3-C, etc.) in as little time as possible. Part B

particularly tests thought processing and attention.72,73 The entire test takes 5 to 10

minutes to complete. Results from both Parts A and B are reported as time required for

completing the task, higher scores therefore, reveal greater impairment. Average times

are 29 and 75 seconds for Tests A and B respectively. Cognitive domains tested by the

TMTA and TMTB includes; attention, concentration, visual scanning, psychomotor speed

32

and sequencing.58,74,75. Both the TMTA and TMTB particularly tests motor speed and

visual attention.75

The other widely used neuropsychological instrument is the Mini-Mental State

Examination (MMSE). It is acknowledged to be the best known and most widely used

cognitive test for dementia screening. 64 This is a 11-question, 30-point test which takes

about 10 minutes to administer.76According to Tamura et al,64 a score of less than 24-

points has a greater than 80% sensitivity and specificity for detecting dementia. Its

item includes orientation, attention, recall, language, and visuo-contruction. It is

standardized and easy to administer and evaluate broad spheres of cognition except

executive function.77 This is why it is an insensitive test for detecting deficits affecting

the frontal lobe. 64, 76 The absence of timed-items, makes it is not insensitive for

detecting disorders characterised by slowing of cognition especially subcortical cognitive

impairment as is seen in vascular cognitive impairment.76MMSE is particularly a poor

instrument in screening for early Alzheimer’s disease. 76, 77

Event-Related Potential (ERP) is the prototype neurophysiological instrument for

cognitive function screening. The ERPs are voltage changes induced within the brain in

response to a variety of cognitive, sensory and motor processes. 78It consist of

sequence of positive and negative fluctuations that are labelled components which are

identified with cognitive, sensory or motor processes embedded in

electroencephalographic activities recorded on the scalp no-invasively. 78, 79

33

The amplitude of ERP provides an index of the extent of neural activation, while latency

reveals the timing of activity.78, 79The fluctuations also called “peaks”, “waves”, or

“components”, are named with a “P” or “N” to indicate positive or negative, and a

number is added to indicate the timing of the peak e.g. “P1” for the first positive peak

or “P300” for a latency of 300 millisecond.79Its recording of reaction time events are

useful in understanding cognitive processes including perception, memory, language

and motor programming. 79 During neurocognitive assessment, patients are asked to

make living/non-living judgements about a series of pictures of objects followed by a

corresponds to the time it takes for subjects to make semantic judgement, this is

recorded as RT with a standardized mean of 542 minutes and a standard deviation of

140 minutes. 78

3.11 Management of Cognitive Impairment in CKD

Identification and treatment of co-morbidities (e.g. anaemia) has yielded improvement

in the overall functioning of patients with CKD.12, 40Given these findings, it is important

to institute routine screening for cognitive impairment in CKD patients. Murray17

proposed predialysis cognitive screening in patients with CKD as this will provide critical

information regarding the benefit versus risks of receiving dialysis. He believes it will

also improve quality of care and outcomes by raising clinicians’ awareness of the

potential effects of cognitive impairment on medication, fluid, dietary compliance and

the ability to make advance directive decisions among dialysis patients. Several non-

pharmacological interventions to manage behavioural, psychological, functional and

34

caregiver needs have to be utilised in the management of CKD patients with cognitive

impairment. These include counsellors, religious support, and health educators’ etc.1

Kurellaetal20advised that though benefits of pharmacological therapy are minimal and

have not been tested in patients with CKD, drugs in development may be efficacious..

They also believe that dialysis care providers may find multidisciplinary approach

positively affecting aspects of the CKD management such as improved medication and

dietary adherence.Tamura et al in their review concluded that there are no published

data on the safety or efficacy of cholinesterase inhibitors and N-methyl aspartate

receptor antagonist in the management of CKD patients. 64

Madero et al1 advise the treatment of blood pressure and dyslipidemia to the targets

recommended in the NKF K/DOQI guidelines being a blood pressure of <140/90mmHg,

a value used by World Health Organization to define hypertention33 and lipids in the

range of triglyceride level of 150mg/dl; low density lipoprotein of <100mg/dl and high

density lipoprotein of 40mg/dl and above.

Several studies have shown that increase of haemoglobin concentration improves

cognitive function.58, 59, 60 Madero et al1 recommended haemoglobin levels between 11

to 12g/dl in all stages of CKD based on the NKF K/DOQI recommendations. Murray

etal24 identified dialysis dose and stroke as potentially modifiable factors associated with

severe cognitive impairment. They also believe that haemoglobin level less than

11.0g/dl was of border line significance. Therefore, slower, gentler, and more frequent

dialysis over a longer period and aggressive stroke prevention, and improved anaemia

35

management were recommended. Pliskinet al80observed no clear cognitive deficit in

CKD patients who had adequate dialysis when compared with people without CKD.

Continuous ambulatory peritoneal dialysis was observed to be of more benefit in

restoring cognitive function than haemodialysis dialysis in CKD patients studied by

Williams et al81

Renal transplant has been shown to improve cognitive function in CKD patients.1, 18,71, 82

Fennell et al49 assessed cognitive function in 20 children and adolescents with end-

stage renal disease 1 to 3 weeks before haemodialysis and at 1 year after successful

kidney transplantation and results were compared with those of a matched control

group. They observed that group with renal disease had marked improvement from

base-line scores at one month after transplant, while there was no significant difference

in performance among the control group. Kramer and his group found that cognitive

dysfunction can be reversed after transplant.83This was confirmed by Grivaet al 84.

Gelbet al 39were of the view that if cognitive impairment does not improve after

transplant, it might be due to the fact that only metabolic derangements improve after

transplant, while other co-morbid conditions linked to CKD remain unchanged.

Finally, assessment of neurocognitive function, allows for early diagnosis, discussion of

prognosis, decisions on management options and as the case may be including end-of-

life care. This will improve understanding and reduce patient and caregiver stress.

36

3.12 JUSTIFICATION FOR THE STUDY

Few reports are available on cognitive function in CKD in Africa generally and Nigeria in

particular. Ogunrinet al13 in Benin used serum creatinine to select patients with chronic

renal impairment (serum creatinine> 3mg/dl). This study, which is in keeping with the

current internationally accepted criteria for classification of CKD, used estimated

glomerular filtration rate. In addition, it evaluated the relationship between serum uric

acid, phosphate, calcium, and anaemia with cognitive performance in patients with

CKD, which were not considered in earlier studies. It is hoped that this study will raise

further awareness and highlight correlates of cognitive impairment in CKD patients. This

ultimately will improve the care and quality of life of patients with CKD, and

subsequently reduce the burden on the care givers.

37

CHAPTER FOUR

MATERIAL AND METHOD

4.1 Study Design and Location

The study was a single centre, observational, case-control study involving patients with

chronic kidney disease seen in the outpatient clinics, wards and the dialysis unit of the

University College Hospital (UCH), Ibadan, south western Nigeria.

4.2 Study Subjects

The subjects were consecutive adult patients seen in the medical wards, medical

outpatient clinic and dialysis unit of UCH with a diagnosis of CKD based on their

estimated Glomerular filtration rate. The controls consisted of consenting healthy

subjects matched for age, gender and educational status, chosen from the hospital

environment including patients, medical and paramedical staff, with no history or

laboratory parameters suggestive of CKD.

4.3 ETHICAL CONSIDERATION

1. Informed consent was obtained from all the subjects involved in the study.

2. Participation was voluntary.

3. Information provided by patients will remain confidential.

4. Ethical clearance was obtained from the Research and Ethical Committee of the

University College Hospital, Ibadan.

38

4.4 PROTOCOL FOR ETHICAL APPROVAL

Invitation to Participate

All eligible participants had the study introduced to them. They were told that

participation at the study was voluntary and that their care will in no way be affected by

their refusing to participate in the study.

Purpose of Study

CKD is a growing global public health problem, with an increasing incidence and

prevalence worldwide. CKD has been reported to be associated with a high incidence

of cognitive impairment. Cognitive function in CKD is a major determinant of quality of

life of patients which is the main focus in their management. Impairment of cognitive

function in CKD could be global or may just affect a component like executive function,

language or memory.

Cognitive impairment contributes to the overall morbidity and mortality of CKD.

Therefore, screening for cognitive impairment in CKD will be beneficial to patients as

physicians will then institute measures to correct the impairment or slow down its

progression.

Confidentiality

Participants were assured of confidentiality as regards all information given by them

regarding their bio-demographic data and other features of their illness. They were

assured that only the investigator and his supervisor would have access to any data

39

obtained and that all materials (electronic and hard copies) would be kept under lock

and key.

Voluntary Participation

Participants were required to give their written or oral consent to participate in the

study with freedom to withdraw from the study at any time. They were guaranteed

respect for their personal and religious beliefs where necessary. All these were

explained fully to all participants in the language they best understand.

Beneficence

There was no monetary benefit for participating in the study and the cost of all

investigations pertaining to the study was borne by the candidate. Participants

benefited by having to know their assessed level of cognitive function.

4.5 Sample Size

The sample size of patients and an equal number of demographically matched controls

was gotten using the formula of difference in proportions stated as follows:85

n = {u √[π1(1-π1) + π0 (1-π0) } + v √[2π̌(1- π̌)]}2 / (π0- π1)2

where;

n is the sample size of each group ( CKD patients and controls).

u is one-side percentage point of the normal distribution corresponding to 100% minus

the power. For a power of 90%, u is equal to 1.28.

40

v is the percentage point of the normal distribution corresponding to the significance

level. For a significance level of 5%, v is equal to 1.96.

π̌= π0+ π1 /2

In the absence of any local studies comparing the proportion of CKD patient with

controls having cognitive impairment, the reference study chosen was that of Etgenet

al. 3From this study, the proportion of patients with moderate to severe CKD having

cognitive impairment (π1) was 21.5%, while the proportion of controls with cognitive

impairment (π0) was 5.8%.

From the above study, the difference in the two proportions (π0- π1) was 15.7

%(0.157), but for the purpose of obtaining a more robust finding, this study aimed at

detecting a difference of 20%(0.200).

n={1.28√(0.215x0.785) +(0.015x0.985) +1.96√2x0.115x0.885}2 / (0.20)2

n={ 1.28√0.169+0.0151 + 1.96√0.204}2 /0.04

n={0.549+0.886}2/0.04

=2.06/0.04

=51.5

This study recruited 79 patients with stages 3 to 5 CKD, and 79 demographically

matched controls.

41

INCLUSION CRITERIA

1. Adults i.e. age >15 years with a diagnosis of stage 3 to 5 CKD using their eGFR.

2. Stages 3 to 5 CKD patients who had consented to take part in the study.

EXCLUSION CRITERIA

1. Patients with a history of cerebrovascular disease.

2. CKD patients in whose consent to participate in the study could not be obtained.

3. CKD patients with comorbid neurological or psychiatric disorder.

4. Patients who had visual or hearing impairment.

5. CKD patients with impaired sensorium.

4.6 CONDUCT OF THE STUDY

Administration of questionnaire

All subjects were interviewed using a structured questionnaire (appendix 1).

Demographic information such as age, sex, occupation, and educational status, was

obtained. Other relevant history included drug and alcohol use, past history of diabetes

mellitus and hypertension, and a history of some of the clinical features of CKD such as

leg swelling, peri-orbital facial puffiness, nausea/vomiting, hiccups and frothy urine. A

general physical and neurological examination was carried out on all subjects.

Assessment of Cognitive Function

Cognitive function was assessed using some items of the Community Screening

Interview for Dementia (CSID) and the Trail marking Test A and B (TMTA and TMTB).

42

The items of the CSID left out are the components used for interviewing close relatives

regarding patients’ activities of daily living. The selected items of the CSID and the Trail

marking test were validated for the diagnosis of cognitive impairment in a subsample of

normal subjects and normative values and cut off scores were obtained. The pretest

population consisted of individuals in the hospital population of both sexes with age

ranging from 15 years to 75 years. Their level of education included primary, secondary

and tertiary education. The mean of the total CSID score from the pretested population

was 57(SD=7) and 2XSD was 14. Cognitive impairment based on performance on CSID

was fixed at total CSID less than 57 minus 2XSD (i.e. any score < 43). The mean TMTA

and TMTB scores from the pretest were 38.5 and 76 seconds respectively. These time

span was below the cut-off point above which subjects are normally judged to be

cognitively impaired based on performance on TMTA and TMTB which are 90 seconds

and 180 seconds respectively, which were the cut-off points used to evaluate subjects

for cognitive impairment in this study.

In patients who had dialysis, the cognitive function was assessed at least twelve hours

after the last dialysis session because the worst time to communicate with dialysis

patients is usually during the dialysis session.17, 64

Subjectshad their blood pressure measured using a mercury sphygmomanometer after

they had rested for about 5 minutes in a sitting position. The measurement of blood

pressure for each patient was rechecked three times and the average calculated. Serum

electrolytes (Sodium, Potassium, Bicarbonate, Phosphate, and Calcium), Urea,

Creatinine, and Uric acid were measured using Hitachi® automated machine under

43

standardized condition in the UCH, chemical pathology laboratory. The packed cell

volume (PCV) was determined by centrifuging heparinised blood in a micro-haematocrit

tube, and the value read with a micro-haematocrit reader.

Creatinine clearance was estimated using the Cockcroft and Gault formula for predicting

Glomerular Filtration (GFR) as follows:30, 39

(140-Age) x weight (Kg) x (0.85 for women)

72 x serum creatinine (mg/dl)

4.7DATA ANALYSIS

Data generated from the study were analysed using the Statistical Package for the

Social Sciences (SPSS) version 16. Results are presented in proses, tables, and

illustrations. Numerical data are presented as means and standard deviation, while

categorical data were presented as frequencies and proportions. Correlation analysis

for biochemical parameters and CKD was done using both the Pearson correlation for

parametric data and Spearman’s ranked correlation non-parametric data. The difference

in frequencies was analysed using chi-square test among the categorical variables,

while the difference between means were tested using the students t-test. Significant

level was set at p-value less than 0.05.

44

CHAPTER FIVE

RESULTS

5.1 SOCIO-DEMOGRAPHIC CHARACTERISTICS

Seventy nine consenting subjects aged 17-72years with stages 3 to 5 CKD and an equal

number of controls matched for age, sex, and educational status formed subjects for

this study.

There were more males patients than females, with a total number of males being 52

(65.8%), and the females were 27 (34.2%). The male to female ratio was 1.9:1.

Only 2 subjects (2.5%) each were aged less than 20years and more than 70 years. The

number of the other patients by their age was 25 (31.6%) 41-50 years; 21 (25.3%) 21-

30 years; and 18 (21.4%) 31-40 years. The mean age of patients was 39.7 years

(SD=11.0), while that of the control was 39.0 years (SD= 11.9)

All the consenting CKD patients had at least a primary school education. The academic

distribution of the CKD patients was as follows; 20 (25.3%) had primary education; 24

(30.45%) had secondary education; and 35 (44.3%) completed tertiary education.

Although there was a slight difference in the educational levels attained by the controls,

it was not statistically significant. The socio-demographic distribution is as shown on

table 1.

45

Table 1. Socio-demographic characteristics of subject

Variable Controls (n = 79 ) CKD patients (n = 79 ) Total (n = 158) Test statistic p - value

Age group (years)

11 – 20 2 (2.5) 2 (2.5) 4 Fishers test 1.000

21 – 30 20 (30.5) 20 (30.5) 40

31 – 40 19 (24.1) 19 (24.1) 38

41 – 50 25 (31.6) 25 (31.6) 50

51 – 60 7 (8.9) 7 (8.9) 14

61 – 70 4 (5.6) 4 (5.6) 8

≥ 71 2 (2.5) 2 (2.5) 4

Sex

Male 52 (65.8) 52 (65.8) 104 Chi square test (0.0) 1.000

Female 27 (34.2) 27 (34.2) 54

Education

None 0 (0.0) 0 (0.0) 0 Chi square test (0.0) 1.000

Primary 20 (25.3) 19 (24.1) 39

Secondary 24 (30.4) 25 (31.6) 49

Tertiary 35 (44.3) 35 (44.3) 70

46

5.2 Mean Blood Pressures, Biochemical Parameters and eGFR of CKD

Patients

The means systolic and diastolic blood pressure, biochemical parameters and estimated

glomerular filtration rate are as show in table 2. The mean systolic blood pressure was

145.0 (26.61) mmHg and the mean diastolic blood pressure was 88.5 (16.77) mmHg.

The mean values of biochemical parameters for the CKD patients were: sodium, 130.1;

potassium,4.6; bicarbonate, 17.5 chloride, urea, creatinine, uric acid, phosphate, and

calcium were, 130.

47

Table 2. Mean Blood Pressures, Biochemical Parameters and eGFR of CKD

Patients

Variables Mean (SD)

systolic blood pressure 145.0 (26.61)

Diastolic blood pressure 88.5 (16.77)

Serum Sodium 130.1 (20.75)

Serum Potassium 4.6 (2.12)

Serum bicarbonate 17.5 (3.63)

Serum chloride 100.5 (12.24)

Serum urea 137.4 (69.07)

serum creatinine 7.7 (5.93)

Egfr 15.9 (10.31)

serum uric acid 10.0 (10.70)

serum phosphate 8.1 (16.93)

serum calcium 7.6 (1.44)

packed cell volume 23.1 (5.45)

48

5.2 Percentage Distribution of the CKD Patients According to the Stage of CKD

Figure 1 is a pie chart showing the distribution of the patients according to their stage

of chronic kidney disease. The greater proportion of the patients 42 (53.2%) had stage

5 CKD, while 28 (35.4%) and 9 (11.4%) were in stages 4 and 3 CKD respectively.

49

Figure 1. Percentage Distribution of the CKD Patients According to the

Disease Stage of CKD

11.40%

35.40%

53.20%

Stage 3 CKD

Stage 4 CKD

Stage 5 CKD

50

5.3 Cumulative Session of Dialysis Undertaken by CKD Patients

Figure 2 is a pie chart showing the total number of dialysis sessions the CKD patients

had undertaken before being recruited for the study. The distributions shows that

majority of the patients had not undergone dialysis before being recruited for this study

despite the fact that most of them are in stages 4 and 5 CKD. Only 6 (7.6%) had six or

more sessions of dialysis, 14 (17.7%) had between one to five sessions of dialysis, and

59 (74.7%) had no dialysis.

51

Figure 2. Cumulative dialysis sessions undertaken by CKD patients

52

5.4 Frequency of Cognitive Impairment Among CKD Patients and Controls

Using the CSID

Figure 3 shows the frequency of cognitive impairment among CKD patients and controls

using the CSID as the screening instrument. The number of CKD patients with cognitive

impairment on the CSID was 41 (51.9%), compared to only 2 controls (2.5%), and this

was statistically significant (p value <0.001). The number of CKD patients without

cognitive impairment was 38 (48.1%) compared to controls which was 77 (97.5%). The

odds ratio for having cognitive impairment in the presence of CKD stages 3 to 5 was

2.026 (95% confidence interval =1.61-2.56).

53

Figure 3. Frequency of cognitive impairment among CKD patients and

controls using CSID

OR=2.026, 95% CI= (1.61-2.56)

51.90%

2.50%

0.00%

10.00%

20.00%

30.00%

40.00%

50.00%

60.00%

CKD Controls

frequency of cognitive impairment

frequency of cognitiveimpairment

54

5.5 Frequency of Cognitive Impairment Among CKD Patients and Controls

Using the TMTA

The proportion of CKD patient and control with cognitive impairment detected using the

TMTA is as shown in table 3. A total of 42 (53.2%) CKD patients had cognitive

impairment, while there was no detectable cognitive impairment among the controls

using the TMTA as screening instrument. This was statistically significant. (p= <0.001).

The odds ratio was 3.13 (95% confidence interval = 2.40 to 4.09).

55

Table 3. Frequency of cognitive impairment among CKD patients and controls

using TMTA

CKD patients Controls Total X2 df p-value

n(%) n(%) n(%)

Present 42 (53.2) 0(0.0) 42(26.6) 57.21 1 <0.001 Absent 37(46.8) 79(100) 116(73.4) Total 79(100) 79(100) 158(100)

OR=3.13, 95% CI = (2.40-4.09)

56

5.6 Frequency of Cognitive Impairment Among CKD Patients and Controls

Using the TMTB

The number of CKD patients with cognitive impairment using TMTB was 22 (40.0%),

but there were no controls with detectable cognitive impairment using this same

instrument. This was statistically significant (p=<0.001). The odds ratio is 3.22 (95%

confidence interval = 2.42 to 4.25). This finding is as shown in table 4.

57

Table 4. Frequency of cognitive impairment among CKD patients and controls

using TMTB

CKD patients Controls Total X2 df p-value

n(%) n(%) n(%)

Present 22 (40.0) 0(0.0) 22(17.2) 35.26 1 <0.001 Absent 33(60.0) 73(100) 106(82.8) Total 55(100) 73(100) 128(100)

OR=3.22 95% CI =(2.42-4.25)

58

5.7 Correlation of CSID Scores in CKD Patients with Biochemical

Parameters, Packed Cell Volume and Blood Pressure

Table 5 shows the correlation of cognitive impairment in CKD patients with their

biochemical parameters (serum urea, creatinine, sodium, potassium, phosphate, uric

acid and calcium), PCV, and blood pressure. Negative weak correlations were found for

urea (r=-0.192, p=0.091), creatinine (r=-0.218, p=0.054), sodium (r=-0.032,

p=0.778), and PCV (r=-0.019, p=0.0870). There was no significant correlation between

cognitive impairment and serum potassium (r=0.041, p=0.718), phosphate (r=0.027,

p=0.810), uric acid (r=0.074, p=0.515), systolic blood pressure (r=0.004, p=0.971) or

diastolic blood pressure (r=0.140, p=0.220). Significant correlation was obtained for

serum calcium (r=0.240; p=0.033) and eGFR (r=0.379; p=0.0006).

59

Table 5. Correlation of CSID Scores in CKD Patients with Biochemical

Parameters, Packed Cell Volume and Blood Pressure

Variable Correlation coefficient p-value

Urea -0.192 0.091 Creatinine -0.218 0.054 Sodium -0.032 0.778 Potassium 0.041 0.718 Phosphate 0.027 0.810 Uric acid 0.074 0.515 Calcium -0.240 0.033 PCV -0.019 0.870 eGFR 0.379 0.0006 SBP 0.004 0.971 DBP 0.140 0.220

(PCV= packed cell volume; eGFR= estimated glomerular filtration rate; SBP= systolic

blood; DBP=diastolic blood pressure)

*Test statistic- Spearman’s ranked correlation

60

5.8 Correlation of TMTA Time in CKD Patients with Biochemical

Parameters, Packed Cell Volume and Blood Pressure

Using the performance of CKD patients on TMTA, there was no significant correlation

between cognitive impairment in the CKD patients and their serum urea, creatinine,

potassium, phosphate, calcium, sodium, uric acid, PCV, eGFR, systolic blood pressure or

diastolic blood pressure. These are shown in table 6.

61

Table 6. Correlation of TMTA Time of CKD Patients with Biochemical

Parameters, Packed Cell Volume and Blood Pressure.

Variables Cognitive impairment (n=79) Correlation coefficient p-value

Urea 0.164 0.149 Creatinine 0.134 0.237 Sodium -0.023 0.884 Potassium 0.078 0.492 Phosphate 0.038 0.743 Uric acid -0.084 0.465 Calcium 0.108 0.346 PCV -0.017 0.885 eGFR -0.201 0.076 SBP -0.046 0.686 DBP -0.047 0.680

* Test statistics- Spearman’s ranked correlation.

62

5.9 Correlation of TMTB Time of CKD Patients and Biochemical Parameters,

Packed Cell Volume and Blood Pressure.

Table 7 shows there was a non-significant positive correlation between urea, creatinine,

sodium, potassium, phosphate, uric acid, calcium, PCV and cognitive impairment in

stages 3 to 5 CKD patients using TMTA as the screening instrument, while eGFR,

systolic blood pressure and diastolic blood pressure had a non-significant negative

correlation.

63

Table 7. Correlation TMTB Time in CKD Patients with Biochemical

Parameters, Packed Cell Volume and Blood Pressure

Variables Correlation coefficient p-value

Urea 0.164 0.234 Creatinine 0.970 0.481 Sodium 0.123 0.347 Potassium 0.021 0.881 Phosphate 0.191 0.162 Uric acid 0.024 0.862 Calcium 0.094 0.491 PCV 0.046 0.742 eGFR -0.135 0.327 SBP -0.141 0.303 DBP -0.123 0.371

*Test statistics-Spearman’s ranked correlation

64

5.10 Multivariate Linear Regression Analysis of Accurate Predictors 0f

Cognitive Impairment Using CSID

The serum calcium and estimated glomerular filtration rate which were parameters with

a strong linear relationship with cognitive impairment were adjusted for using

multivariate linear regression technique. The result is as shown in table 8. Serum

calcium has no predictive value (β=-0.159, p=0.132), while estimated glomerular

filtration rate has a strong predictive value (β=0.378, p=<0.001).

65

Table 8. Multivariate Linear Regression Analysis of Accurate Predictors of

Cognitive Impairment Using CSID

Variable Regression

coefficient (β)

95% CI for β P value

Serum calcium

-0.159

0.1-0.350

<0.132

Egfr

0.378

-1.560-0.208

<0.001

66

5.11 Comparism of the Mean CSID Performance between Controls and CKD

Patients

In comparing the mean performance of the controls and CKD patients, the mean CSID

scores is lower among CKD patients. All the cognitive domains assessed by the

elements of CSID recorded lower scores for the CKD patients when compared to

controls.Statistically significant lower scores were only obtained for language(naming)

(t=13.100, p=<0.001), language(fluency), (t=9.760, p=<0.001), attention and

calculation (t=3.098,p=<0.001), orientation in place (t=4.048,p=<0.001), immediate

recall (t=8.497, p=<0.001), and praxis (t=10.504, p=<0.001). This is shown in table 9.

67

Table 9. Comparism of the Mean CSID Performance between Controls and

CKD Patients

Variable (N) Mean (SD) t-value Significant level (p value)

Total CSID Control CKD Total

79 79 158

54.0(5.0) 42.6(5.9)

13.10

<0.001

Language(naming) Controls CKD Total

79 79 158

6.9(0.4) 5.7(0.8)

11.78

<0.001

Language(definition) Controls CKD Total

79 79 158

4.0(0.1) 3.9(0.4)

1.73

0.164

Language(fluency) Control CKD Total

79 79 158

15.6(4.2) 9.4(3.8)

9.76

<0.001

Attention & calculation Controls CKD Total

79 79 158

3.0(0.1) 2.8(0.6)

3.10

<0.001

Orientation(time) Controls CKD Total

79 79 158

4.9(0.3) 4.6(1.1)

2.26

0.019

Orientation(place) Controls CKD Total

79 79 158

4.9(0.5) 4.5(0.8)

4.05

<0.001

Memory(Immediate recall) Controls CKD Total

79 79 158

4.6(0.5) 4.5(1.3)

8.50

<0.001

Memory(registration) Controls CKD Total

79 79 158

3.1(0.4) 3.0(0.3)

0.47

0.256

Praxis Controls CKD Total

79 79 158

6.9(0.4) 5.3(1.3)

10.50

<0.001

68

5.12 Comparism of the Mean Time Taken to Complete TMTA and TMTB

between Controls and CKD Patients

Table 10 compares the mean time taken in second to complete TMTA and TMTB. It

took the CKD patients a mean of 102.6 seconds to complete the TMTA, which was

much longer than the time taken by the controls which was 44.6 seconds, the

difference was statistically significant ( p=<0.001). This value was much longer than

the cut-off point of 60 seconds for defining cognitive impairment. It took the CKD

patients an average of 169.5 seconds to complete the TMTB compared to 78.3 second

used by the controls. This was also statistically significant (p=<0.001).

69

Table 10. Comparism of the Mean Time Taken to Complete TMTA and TMTB

Among the Controls and CKD Patients

Variable

(N)

Mean time in

seconds (SD)

t-value

df

Significant

level

(p value)

TMTA

Controls

CKD patients

Total

79

79

158

44.6(16.7)

102.6(43.6)

67.848

156

<0.001

TMTB

Controls

CKD patients

Total

55

55

110

78.3(28.9)

169.5(56.0)

27.20

126

<0.001

70

CHAPTER SIX

DISCUSSION

6.1 Patient Characteristics.

This cross-sectional study examined neurocognitive function using CSID, TMTA and

TMTB among patients with stages 3 to 5 CKD and compared the findings with that of

controls. It involved 79 CKD patients who were matched for age, sex and educational

status with the controls. A similar study carried out in this country15, 25involved 66 pre-

dialysis patients who were demographically matched with an equal number of controls.

This study involved patients across all age ranges, with majority of the patients (31.6%)

being between the ages of 41-50 years. This is similar to the age distribution of the

patients studied by Ogunrin AO et al15, 25, and is therefore different from most studies

carried out in western subjects which mostly assessed cognitive function in elderly

patients with CKD.3, 31, 74

This study had more males subjects than females with the ratio of males to females

being 1.9:1. Ogunrinet al15 observed a female preponderance but with male to female

ratio of 1:1.3. Etgenet al in the INVADE study3 had a more males in the study, the

male to female ratio was greater than 15:1. The INVADE study however took place in a

Western country. These differences in male to female ratio may be due to the different

sampling method employed in these studies. While this study and that of Ogunrin

recruited consecutive patients presenting in the hospital, the INVADE study was a

community based study.

71

This study observed that a greater proportion of the CKD patients were in stages 4 and

5 CKD which constituted 35.4% and 53.2% respectively. This is likely due to the fact

that patient in this climes usual present late in CKD when they are symptomatic. A

similar pattern of distribution was observed previously by Alebiosu et al9. These patients

therefore would require dialysis, but however this study observed that majority of the

patients (74.4%) had no dialysis which might have had a negative effect on their

cognitive performances. Gelb etal86 had a unique selection of patients in their study;

these included 42 renal transplant patients, 45 pre-dialysis patients and 49 controls.

Their patient selection was to enable them compare the impact of transplant on

cognitive function.

6.2 Cognitive Screening Instruments

Different cognitive screening instruments have been utilised in different studies to

assess cognitive function in CKD patients including Iron-psychological test battery

(FePsy)15, the 6-item Cognitive Impairment Test (6CIT)3, Modified Mini-Mental Scale

Examination (3MS)24, 31, 74, Trail marking test A (TMTA)23 and Trail marking test B

(TMTB)31, 74, Mini Mental State Examination (MMSE)23, Event-related potential (ERP)23,

and California Verbal Learning Trial (CVLT)23among others. This study is apparently

the first to utilize the CSID to assess cognitive function in CKD patients. The high

sensitivity and specificity of the CSID quoted as 87% and 83% respectively in the

literate and non-literate populations, and adaptability to our African setting is supported

by its ability to detect cognitive impairment among controls in this study even when

TMTA and TMTB could not detect any cognitive impairment among this group of

72

subjects. About 56% of the subjects in this study had a secondary school certificate or

less.

It will be interesting to compare the sensitivity and specificity of the CSID with that of

events-related potential which Madanet al believed to be the most sensitive instrument

for detecting cognitive impairment in CKD. In their study of neurologically asymptomatic

(MMSE >24) CKD patients, they were able to demonstrate P300 latency changes

indicating cognitive deficits.23

6.4 Proportion of Patients with Cognitive Impairment

A few studies evaluated mainly pre-dialysis CKD patients1, 25, 82, while others enrolled

CKD patients undergoing dialysis23, 24. This study like that undertaken by Kurellaet al3, 31

included both pre-dialysis and dialysed patients. Proportion of CKD patients with

cognitive impairment compared with that of controls from these studies are slightly

different. This study noted a slight difference in proportions of patients and controls

when using the different neuro-psychological assessing instruments. The proportion

with cognitive impairment among CKD patients was 51.9%, 53.2% and 40.0% using

CSID, TMTA and TMTB respectively. These findings are slightly higher than the

frequencies reported in previous studies. Kurellaet al31 comparing cognitive performance

of eighty patients in stages 3 to 4 CKD with that of eighty patients in stage 5 CKD,

observed that 38% of the patients with end-stage renal disease, 23% of the patients

with advanced kidney disease and 5% of the patients with mild-to-moderate CKD had

cognitive impairment. The INVADE study3,on the other hand, reported similar findings

73

among patients with CKD, with values of 9.9% among patients with mild CKD and

21.5% among patients with advanced CKD. Interestingly however, they observed that

5.8% of the normal subjects had cognitive impairment, which was higher than the

2.5% observed among controls in this study. This slightly higher proportion might be

due to the fact that the INVADE study considered mainly elderly community dwellers,

unlike this study which had only 7.6% of the patients above 60 years. Advancing age is

associated with most of the traditional risk factors for cognitive impairment and

cerebrovascular diseases such as hypertension, diabetes mellitus and dyslipidemia.3, 12,31

In another study, Murray et al24 classified 38% of the primary sample of 338

haemodialysis patients with cognitive impairment, which was also lower than the

proportions observed in this study. It is difficult to explain the high prevalence of

cognitive impairment in this study. The possibilities could include the effect of other risk

factors for cognitive impairment such as depression and use of centrally acting

antihypertensive medications such as alpha methyldopa in these patients. The challenge

of procuring dialysis and the financial burden of sustaining such treatment in a third

world country might be risk factors for depression in these CKD patients. The negative

impact of central nervous system acting medications on cognitive function was

contradicted by the finding of no association between use of β-blockers and central

nervous system acting medications and cognitive function by a previous study31.

CKD has been found to be an independent risk factor for cognitive impairment.22,31The

odds ratio of developing cognitive impairment in the presence of CKD using CSID for

assessment was 2.026. Kurellaet al48on evaluation of menopausal women with

74

eGFR<30ml/minute per 1.73m2 found a four-fold greater odds of cognitive impairment

compared to women with eGFR>60ml/minute per 1.73m2, independent of age, race

and other confounding factors. Seligeret al in another study 57, observed that there was

over 25% increase risk of dementia in an individual with creatinine clearance of 2.0

mg/dl compared to those with creatinine of 1.0 mg/dl.

6.5 Predictors of Cognitive Impairment in Patients with CKD

Previous studies had documented conflicting correlations between serum electrolytes,

urea, creatinine, blood pressure, eGFR and haemoglobin concentration (or PCV) with

cognitive function in CKD patients. These parameters could be helpful in predicting the

cognitive status of the patients where tools for detail assessment or trained personnel

are not available. In this study, cognitive performances using TMTA and TMTB did not

demonstrate any statistically significant correlations between any of the above

mentioned variables with cognitive function in our CKD patients. But the CSID

demonstrated a weak positive correlation between serum creatinine and cognitive

impairment ( r=0.218; p=0.054). There was a statistically significant positive correlation

between cognitive impairment with serum calcium (r=0.240; p=0.033) and eGFR

(r=0.379; p=0.0006). These findings are similar to that documented by Ogunrinet al25.

They had documented a negative correlation between creatinine and cognitive

parameters such as auditory time and visual reaction. Additionally, after multiple logistic

analyses, they noted negative correlation between cognitive performance with

creatinine, urea and hypertension. Kurellaet al31 found no association between global

cognitive function or executive function and clinical factors such as PCV, serum calcium,

75

albumin, cholesterol, parathyroid hormone and aluminium. Murrayet al 24on bivariate

analysis observed that haemoglobin levels less than 11.0g/dl was associated with

cognitive impairment. This relationship between haemoglobin/PCV and cognitive

function in CKD could not be confirmed in this study probably because most of the

patients had blood transfusion before being evaluated.

In keeping with the findings of this study, several studies have documented a

significant correlation between renal function determined by eGFR or serum creatinine

with cognitive function. It was observed in this study that as eGFR decreased, cognitive

impairment increased. Among the sixty-consecutive renal patients studied by Ogunrinet

al15creatinine level was observed as the most potent factor affecting the memory

performances of subjects.Slininet al74 in a study of community dwelling men found an

independent association between low eGFR and poorer cognitive performances on

TMTB and 3MS, findings also noted by Kurellaet al31. After a multivariate logistic

regression analysis of accurate predictors of cognitive impairment using CSID showed a

weak predictive value for serum calcium compared to that of eGFR, which is in keeping

with findings in these studies.

6.6 Pattern of Cognitive Impairment in CKD Patients

CSID like MMSE and 3MS are neuropsychological tools for assessing global cognitive

function, while TMTA and TMTB predominantly evaluate attention, concentration,

psychomotor speed, cognitive shifting and complexing which are functions localised to

the frontal lobe. It has been hypothesised that in the early stages of CKD, frontal lobe

functions are selectively impaired, but at the later stages global cognitive function is

76

impaired.31, 74, 87. This study showed that in all the cognitive domain assessed by CSID

including language (naming/definition/fluency), attention, calculation, orientation

(place/time), memory (registration and immediate recall) and executive functions, CKD

patients performed worse than the controls. The total CSID scores of CKD patients were

lower than those of controls and the pre-test population. The widest variability of total

CSID score within the different groups was recorded for the pre-test population. This is

probably due to the greater heterogeneity of the pre-test population. This study further

demonstrated statistically significant poorer performance on TMTA and TMTB in CKD

patients than controls demonstrating the presence of impairment of frontal lobe

executive functions in CKD patients with stages 3 to 5 CKD. Other cognitive domains

with significant impairment in CKD patients compared to the controls in this study were

language (naming), language (fluency), attention and calculation, orientation in place,

immediate recall, and praxis. One would conclude therefore, that this study in addition

to demonstrating impairment in executive function, the CKD patients also had some

impairment of global cognitive function. Ogunrinet al15, 25 showed that CKD patients

performed poorly on visual/auditory reaction time task, and verbal/non-verbal memory

task compared to the controls. With respect to concentration and attention, the renal

failure patients in their study compared favourably with the controls on binary choice

reaction task. Their findings regarding concentration and attention are not in keeping

with reports from other findings of global cognitive impairment among CKD patients30.

Slininet al74, and Kurellaet al31 found an association between mild to moderate kidney

disease and poor performance on TMTB. This supports the hypothesis that early CKD is

77

mainly associated with executive dysfunction. Gelb et al 86observed that when cognitive

functions in CKD patients were compared between controls and post-transplant renal

patients, CKD patients had significantly worse verbal learning, verbal memory and set-

shifting task compared to other groups of subjects.

78

CHAPTER SEVEN

CONCLUSIONS, RECOMMENDATIONS AND LIMITATIONS

CONCLUSIONS

1. Cognitive impairment is higher in patients with stages 3 to 5 CKD patients than

demographically matched non chronic kidney disease subjects.

2. There is impairment of executive function, language, attention, calculation,

orientation in place, immediate recall and praxis among patients with stages 3 to

5 CKD.

3. Estimated glomerular filtration rate and the stage of chronic kidney disease are

the best predictors of cognitive impairment in patients with CKD.

LIMITATIONS OF THE STUDY

1. Inclusion of both pre-dialysed and dialysed patients among the cases did not

allow for a comparative study of the benefit of dialysis on cognitive function.

2. Time constraints did not allow for a prospective study that would have followed

the progression of cognitive deficit in patients with CKD as renal function decline

and possible benefits of renal transplant in Nigerian-Africans.

3. Assessment of patients after dialysis, blood transfusion and other treatment

measures were initiated would have influenced the findings in this study.

79

4. The estimation of eGFR from serum creatinine rather than being measured

directly may give unduly high or low values in certain patients including the

obese ones.88

RECOMMENDATIONS

1. In view of the high prevalence of cognitive impairment in CKD, it will be ideal to

routinely evaluate all CKD patients for cognitive impairment.

2. A prospective study to evaluate baseline cognitive function in CKD patients and

subsequent changes in cognitive function as renal function declines would be

highly beneficial.

3. It will also be necessary to evaluate the impact of cognitive decline in CKD on

hospital stay and utilization of health resources.

4. In view of the high prevalence of global cognitive dysfunction as renal function

declines decision making at certain stages of CKD should not be left to the

patients alone as their decision making might be impaired.

80

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APPENDIX 1

CONSENT DOCUMENT

To be read out to patients before consultation starts.

I am Dr Uduak Effiong Williams of the department of internal medicine at the

University College Hospital, Ibadan.

I am conducting a study on “Assessment of Cognitive function in Patients with

Chronic Kidney Disease Stages 3 to 5 at the University College Hospital, Ibadan”

You are hereby invited to take part in the study.

Please note that any information we receive from you will be kept secret and your

name will not appear directly in the record.

You will be required to have your blood samples taken for some investigations.

The purpose and the procedure of this study had been explained to me and I

agree to participate in the study.

----------------------------- -------------------------------

Signature/thumb printing Signature of Investigator

of subject.

-------------------------------- ------------------------------

Date Date

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APPENDIX 2

IWE-MO GBO-MO BGA

A o kaa fun Olukopaki a to bereiwadi.

Emi Uduak Effiong Williams ti mo je osise ile iwosan Orita- mefa Ibadan.

Mo nse iwadi lori “Ayewo nipa sise opolo lara awon alaisan Kidirin ni ile –

iwosan Orita – mefa, Ibadan’’ .

Mo pe yin latiko pa nibe.

Gbogbo ohun ti e ba so fun wa, la o fi se oro asiri, oruko yin koni jade ninu iwewa.

A o si gba eje yin fun awon ayewo kan.

Won ti salaye fun mi lekun rere nipa iwadi yi, mo si ti gba lati kopa nibe.

............................. ..............................

Signature/ ika-tite. ika- awadi / doctor.

............................. ...............................

Ojo Ojo

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APPENDIX 3

ASSESSMENT OF COGNITIVE FUNCTION IN PATIENTS WITH STAGE 3 TO 5

CHRONIC KIDNEY DISEASE AT THE UNIVERSITY COLLEGE HOSPITAL, IBADAN.

A.DEMOGRAPHIC INFORMATION

Name (Initials)..............................................................................

Serial No..................................Hospital No..................................

Age....................Sex...................Religion....................................

Educational status......................................................................

Occupation.................................................................................

Duration of illness......................................................................

B. SYMPTOMS

Facial swelling........ Leg swelling........... Frothy urine............

Nausea/vomiting.......... Change in urine volume...................Hiccups.............

C. DRUG HISTORY

....................................................................................................................................

.................................................................................................................................

D. ALCOHOL HISTORY

Type (wine, gin, beer)............................... Quantity............................................

Duration of alcohol use...................................

E. PHYSICAL EXAMINATION

(i) Anthropometry: Weight.............. Height..............

(ii) General Examination: Pallor........... Oedema................ Jaundice..............

Scratch marks..................

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(iii) Neurologic examination:

Asterixis................ Seizures..............

Motor system................................................................................

(iv) CVS. Pulse................................ Blood Pressure................mmHg

F. INVESTIGATIONS

(i) Electrolyte/ Urea/ Creatinine:

Na+.......................................................

K+..........................................................

HCO2-.....................................................

PO2-.......................................................

Ca2+.......................................................

Urea......................................................

Creatinine..............................................

Estimated GFR........................................

(ii) Packed Cell Volume.............................

(iii) Serum Uric Acid.................................

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APPENDIX 4

TRAIL MARKING TEST A

Patients Name.................................. Serial No...................

95

APPENDIX 5

TRAIL MARKING TEST B

Patient’s.............................Serial No..........................

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APPENDIX 6

SELECTED ELEMENTS OF CSID

A) Language expression- Naming

We will begin with naming things. I will point to something and I would like for you to tell to me

the name of the object. For example…

A o berepelusisoorukoawonorisirisinkan. Ti moba tin a owosinkanna, emiyiofeki e so oruko re

fun mi. APejuwe: (Mo fi owokaneti) ____________kiniyi?

Show your pencil.

1.What is this called? 0….Incorrect

Ki ni an peeleyi 1….Correct

Point to your watch

2.What is this? 0…Incorrect

Kiniyi? 1…Correct

Pat your chair

3.What about this… 0…Incorrect

Eletinnko? 1…Correct

Point to shoes

4.And these…. 0…Incorrect

Ati a won eyi? 1…Correct

Show your knuckles.

1. What do we call these? 0…Incorrect

Kini a npeeleyi? 1…Correct

Point to the elbow.

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2. What do we call this? 0…Incorrect

Kini a npeeyi? 1…Correct

Point to the shoulder.

3. And this, what do we call this part of our body? 0…Incorrect

Kini a se npeeyaaratimo fi owokanyi? 1…Correct

B) Language Expression – Definition

I was just showing you thing and you told me what we call them. Now I will tell you the name of

something and I want you to describe what it is. For example…

Mo tinfiawonnkahan yin, e siti so orukoti a npe won fun mi. nisisiyiemi s so orukonkankan

fun nyin. Emi o sifeki e juwenkantiaqwonna je. Gegebuapejuwe… oko: a nfikoebe.

4. What is a bridge?

Kiniafara je?

(Examples of correct answer: something that goes across a river, canyon, road.)

(Lati da omikoja) 0...Incorrect

____________________ 1…Correct

5. What do you do with a hammer?

Kini a nfi hammer se?

(Examples of correct answer: drive nails, build things, bang things.)

(lati fi kaniso, lati fi koila.) 0…incorrect

________________________ 1…Correct

6. What do people do in a church/mosque?

(Examples of correct answer: pray, sing, praise God, read, meditate, etc.)

Kiniawonenia ma nseniSositabiMosalasi?

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Latigbadura - To pray

Lati sin Olorun - To worship God

LatiKorin - To sing

LatiKewu - To read Quran

Latigbeyawo - Towed 0…Incorrect

Awonmiran - (Others)_________________ 1…Correct

7. Where do we buy medicine?

(Examples of correct answer: drug store, pharmacy, special section of

supermarket…)

Nibonietinraoogun? 0…Incorrect

__________________ 1…Correct

C) Memory - Recall

8. Do you remember my name? what is it? 0…incorrect

Nje e rantioruko mi? kini? 1…Correct

9. If Incorrect: well, I’ll ask you again very soon. Remember

My last name is___________________________.

Ma tun bi yin nioruko mi laipeyi. E rantipeoruko mi nje___________________

(repeat 3 times if necessary, rough approximation

of name is acceptable.)

D) Language Expression – Name, Fluency

10. Now we are going to do something a little different, I am going to give you a category

and I want you to name, as fast as you can, all of the things belong in that category. For

example, if I say ‘articles of clothing,’ you could say shirt, tie or hat. Can you think of

other articles of clothing?

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Nisisiyi, ao se awonnkanmiranti o yato die sieleyiti a tin se bo. Emi a fun yin niorukoti

a nfijuweawonnkankan. Emi a sifeki e daruko bi e bati le yara so gbogboawonnkanti e

bamoti o ‘jemoorukonaa. Ni apejuwe, timoba so wipe “Asoti a wo”, eyin le so agbada,

dandogo, singilet, ibante, gele).

That’s fine. I want you to name things that belong to another category ‘animals’.

I want you to think about all the many different kinds of animals you know. Think of any

kind of animal in the air, on land, in the water, in the forest, all the different animals.

Now I would like for you to tell the names for as many different animals as you can. You

will have a minute to fdo this. (Interviewer – look at your watch.) are you ready? Let’s

begin…

Iyendara. Mo feki e darukoawonnkanti ale so penwonje elemi, yatosieniaatiigi. E le da

orukoorisirisi: Orisirisiawonerankoiletabitiigbo, awoneiyeojuorunatitiile,

awonejainuomi (atiosa, atiokun). Mo feki a berenisisiyilati ma darukonwon.

Isejukanni a fun yin latidarukoawonorisiriseranko, eiye, ejati e ba mo. O se Pataki ki e

yaradarukogbogboerankoti e bamoniisejukanyi, nitoriiyeti e ba le darukonimofeka. O

ya o’

Record number of animals______________________

E) Registration

Now I am going to tell you three words and I would like for

You to repeat them after me.

Nisisiyiemi a so oro meta fun yin tie mi a feki e petele mi

11. Repeat after me these words:

(E peawonorowonyitele mi: Oko, Ile, Eja).

Oko (Boat) 0…Incorrect

100

1…correct

Ile(house) 0…Incorrect

1…correct

Eja (Fish)

0…Incorrect

1…correct

(Repeat, up to 5 attempts, until subject has successfully said the three words).

Record number of attempts______________

Very good, now try to remember these words because I will be asking you later.

O darapupo. Ma feki e fi awonoro meta ti a sese so yos’okan, nitoriemi a tun bi yin

lerenipanwaonlaipeyi.

F) Attention and Calculation

Now we’re going to do some things with numbers. This is something hard for people, just try

to do the best you can.

Nisisiyi a fe se isiro die. Isiro ma nniranigbamiranfrunawonenia. Sugbonmofeki e saipa yin ki

e si se iwonti e le se.

12. If I have 20 Naira and give you 2 Niara, how many naira would

I have left? N18.00

Ti mobaniogunNiara, timosi fun yin ni 0…Incorrect

Naira meji, eelo lo kusiowo mi? 1…Correct

G) Recall

13. Do you remember that three words I told you Oko (Boat)

0…Incorrect

a few minutes ago? 1…correct

Ile (house)

0…Incorrect

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1…correct

Nje e rantiawonoro meta timo so fun yin ni Eja (Fish)

0…Incorrect

iwoniseju die ti o koja 1…correct

H) Attention and Calculation

14. If one sweet costs 2 Naira, how much would 2 sweets costs? 0...Incorrect (N4)

1...correct

15. How much would 3 sweets cost? 0...Incorrect (N6)

1...Correct

Ti ekoagidikanba je Naira meji, elonimejiyio je?

Meta nko, Merinnko?

I) Orientation to Place

Now I would like to ask some questions about your home, this area.

Nisisiyi, ma fe bi yin ile/agbegbe yin.

16. What is the name of this city?

0…Incorrect

Kiniorukoiluti a wayi? 1…Correct

____________________________

Who is the Traditional ruler of this city? 0...Incorrect

1...Correct

KiniOrukoobailuyi?

____________________________

17. What are two major streets near your home?

0…Incorrect

Kinioruko tit nlamejiti o wanitosiile yin? 1…Correct

____________________________

18. Where is the city market?

0…Incorrect

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Niboniojanlawa? 1…Correct

____________________________

19. What is your address?

0…Incorrect

Kiniorukoagbo-ile yin? 1…Correct

J) Orientation to Time

Now I would like to ask some questions about time.

20. What day of the week is it? 0…Incorrect

Kiniojoonijkeninuose? 1…Correct

____________________________

21. What month is it?

0…Incorrect

Osukeloni a wayi 1…Correct

22. What year is this?

0…Incorrect

Nje e le so fun mi odunwoni a wayi? 1…Correct

23. What season is it?

0…Incorrect

Kiniigbati a wayi? Igbaojo, erun, tabioye? 1…Correct

24. Did it rain yesterday?

0…Incorrect

Njeojorolana? 1…Correct

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K) Language Comprehension – Motor Response

I am going to ask you to carry out some actions so please listen carefully because I will only tell

you one time. [Interviewer – give complete instructions at one time, do not give them step by

step].

Emi yioniki e se awonnkankan. Nitoripeekansosoniemiyio so nkantimofeki e se yi, o se Pataki

ki e f’eti sile dada

25. Please nod your head.

0…Incorrect

E jowo e fi ori yin se apejuwebeni. 1…Correct

26. Please point first to the window and then to the door.

0…Incorrect

Mo feki e kokonaowosiferese, ki e wanaowosiilekun 1…Correct

[should the subject not complete the full sequence, then the whole instruction may be

repeated to ensure it has been heard and understood].

27. I’m going to give you a piece of paper. When I do,

take the page in your right hand, fold the paper Right Hand

0…Incorrect

in half with both hands, and put the paper down 1…Correct

on your lap.

Folds

0…Incorrect

Emi yio fun nyinni paper (takadi) yi. T mbati 1…Correct

fun yin ni paper na, e fi owootun yin gba, In Lap

0…Incorrect

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ki e kasimejipeluowo yin mejeji, ki e si fi si 1…Correct

oriitan yin.

L) Memory – Recall

28. Do you remember my name? (close approximation acceptable as correct)

0…Incorrect

Nje e rantioruko mi? 1…Correct

M) Praxis – Copying

Now I would like for you to take my pencil and copy these figures in the space below.

Nisisiyiemifeki e mu pencil, nkanti a nko we, ki e siyaawonaworanyigangegebi a tiyasibi

33 34

Incorrect....0 Incorrect....0

Correct......1 Correct......1

105