Cognitive function assessment in patients with end- stage renal disease in Nigeria: A single center experience.

AIM: The purpose of this comparative study was to evaluate cognitive function in end-stage renal disease (ESRD) patients in comparison with age, sex, and level of education-matched control.
MATERIALS AND METHODS: This is a cross-sectional study involving 80 ESRD patients receiving maintenance hemodialysis treatment and recruited conservatively at the nephrology unit of our hospital. Eighty apparently healthy control, that were matched with the patients for age, sex and education, were also recruited. Following exclusion of depression and severe functional disability, a computer-assisted neuropsychological test, the FePsy, was used to assess  memory, psychomotor speed, concentration and attention using simple auditory and visual reaction time tasks, recognition memory tests (RMTs), finger tapping task, and binary choice task (BCT) for both the ESRD patients and controls.
RESULTS: ESRD patients performed worse on simple auditory and visual reaction time tasks (P < 0.05), RMTs (P < 0.05), finger tapping task (P < 0.05), BCT, and computerized visual search task (P < 0.05).
CONCLUSION: Performance in memory, psychomotor tasks, concentration, and attention tasks were found to be reduced among patients with ESRD compared with age, sex and level of education-matched control.

Introduction

Chronic kidney disease (CKD) is increasingly a public health problem.[1] It is characterized by progressive destruction of renal mass with irreversible sclerosis and loss of nephrons over a period of at least months to many years, depending on the underlying etiology.[2] Cognitive impairment is common in end-stage renal disease (ESRD) patients in comparison with the general population.[34] Previous studies have shown that CKD influences the cognitive function of adults.[5] Cognitive dysfunction may occur as a result of deficits in a number of domains of cognition including concentration, judgment, abstraction, memory, and executive function and this may impair the patients’ capability. There is a growing body of evidence that CKD is associated with comorbidities such as hypertension, diabetes mellitus (DM), hyperlipidemia, and stroke that are known to increase the risk of cognitive impairment.[67] Earlier studies have demonstrated that renal transplantation is associated with improvements in both neuropsychological tests such as the mini-mental state examination (MMSE), and neurophysiological markers of cognitive function measured using evoked potential latencies and electroencephalographic rhythms.[8910] This cognitive impairment does not only have implication for the patient's ability to participate in adequate care of the ESRD[3] but also have major implications for informed consent in relation to dialysis initiation or maintenance, and ultimately, renal transplantation.[1112]

In spite of the importance of knowing cognitive status of patients with ESRD, there is limited data, particularly from the developing countries where CKD is increasingly becoming a major public health problem. The purpose of this comparative study was to evaluate cognitive function in ESRD patients in comparison with age, sex and level of education-matched control.

Materials and Methods

Participants and study design

The study was cross-sectional in design. Eighty ESRD patients on maintenance hemodialysis, who consented to participate in the study, were recruited consecutively from the dialysis unit of Aminu Kano Teaching Hospital (AKTH) during the study period (from June 2010 to June 2014). Eighty healthy, age, sex and level of education-matched controls recruited from the general out-patient clinic and healthy volunteers among members of staff of the hospital.

The exclusion criteria were age <18 years, education <6 years, presence of comorbidities that could cause cognitive dysfunction (e.g., DM, hypertension, epilepsy, other metabolic diseases, cerebrovascular disease, Parkinson's disease, epilepsy, human immunodeficiency virus, brain tumor etc., subjects with psychiatric disorders were also excluded). Other exclusion criteria included drug abuse, current use of psychoactive drugs, history of pervious head injury with loss of consciousness, severe functional impairment (Karnofsky performance <50%, alcohol intake, presence of cardiac failure and use of anti-cholinergic medications). The same exclusion criteria were applied to the normal control subjects. A questionnaire was developed and applied to all subjects and emphasis in the questionnaire was on sociodemographic, anthropometric CKD-related data. The study participants were evaluated by way of a detailed general physical and neurological examination.

Data sources

Using a questionnaire-based proforma, we obtained information on sociodemographic characteristics and CKD-related information, history of hypertension, heart disease, previous stroke, and diabetes. Subsequently, all the patients had screening for functional performance and depression using Karnofsky scale and Hamilton and Anxiety Depression Scale (HADS) respectively. Those with Karnofsky performance more than 50% and no evidence of depression on HADS proceeded with the study. Results of blood count, coagulation tests, serum electrolytes, and glucose and renal function tests (urea, creatinine levels) were also obtained in cases.

Cognitive function measure

The cognitive assessment was conducted with the aid of a computer-assisted neuropsychological test battery called iron psychology (“FePsy” version 6.8, The Psychology company, Amsterdam, Netherlands).[13] FePsy, “The Iron Psyche” is a system for automated neuropsychological testing. It contains a set of highly sensitive computerized tests for cognitive neuropsychological functions and a relational database system for storage of the results.[13] FePsy had been validated for use in studies of cognitive functions.[1415] The FePsy test has been validated for use among Nigerians and in patients with chronic renal impairment.[1516] The tests employed in the present study included simple reaction time task, binary choice reaction time, computerized visual scanning task, recognition memory task and finger tapping test. The tests were administered in a quiet and well-lit room at a room temperature with the subject sitting at distance of 40–60 cm from the visual display screen of the computer. The memory function was assessed using the recognition memory test (RMT-word and figure). Mental or psychomotor speed was assessed using the simple reaction time test (auditory and visual). Binary choice task (BCT), which is a complex form of continuous performance test, was used in the study to assess psychomotor speed, attention, and concentration. The computer-assisted visual scanning task (CVST). Which could be used to detect presence of brain damage in the subject reflects accuracy and speed of responses and are evaluated within the context of visual (complex) information processing and perceptual-mental strategies.[15] Finger tapping test was also performed in the context of motor activation and fluency.

The higher the mean scores on auditory reaction test, visual reaction test, and computerized visual search task the poorer the cognitive performance. Conversely the higher the mean scores on recognition test, BCT, and tapping task (which are expressed as correct percent of total) the better the cognitive performance.

On conducting these neuropsychological tests, care was taken to ensure good brightness and contrast of screen, sufficient sound level of the speaker and to elucidate a history of photosensitive seizure from the patients.

Data analysis

Analysis of data was done using GraphPad Prism version 5.03 (GraphPad Software, Inc., CA 92037, USA). The normality of the numerical data was assessed using D’Agostino and Pearson Omnibus tests. Numerical data that were normally distributed were expressed as the mean ± standard deviation (SD). Comparisons of cognitive function parameters between ESRD patients and control subjects were performed using Student's independent sample t-test and Mann–Whitney test in the case of parametric and nonparametric data respectively. P <0.05 was considered statistically significant.

Ethical approval was obtained from the Ethical Committee of AKTH.

Results

During the study period, 80 patients and 80 age- and sex-matched control comprising 45 (56.2%) males and 35 (43.8%) females, in each arm, were evaluated. The mean age ± SD of the patients, were 49.85 ± 10.58 and 49.84 ± 10.55, respectively, the difference in their age was not statistically significant (P = 0.990). The median duration of CKD from diagnosis was 2 years (range 0.2–5 years) [Table 1].

Table 1

Sociodemographic, clinical and laboratory characteristics of the study participants

Variable	ESRD patients (%)	Control (%)	P
Mean age	49.85±10.58	49.84±10.55	0.990
Sex
Male	45	45	1.000
Female	35	35
Level of education
Primary	8 (10)	8 (10)	1.000
Secondary	50 (62.5)	50 (62.5)
Tertiary	22 (27.5)	22 (27.5)
Occupation
Civil service	28 (35)	30 (37.5)	0.848
Homemaker	19 (23.8)	20 (25)
Farming	10 (12.5)	7 (8.75)
Trading	10 (12.5)	10 (12.5)
Student	5 (6.3)	8 (6.3)
Others	8 (10)	5 (10)
Etiology
Chronic glomerulonephritis	35 (43.8)
DM	9 (11.3)
Hypertension	29 (36.3)
Hypertension + DM	6 (7.5)
Undefined	1 (1.3)
Mean creatinine level	486.72±266.4
Mean urea level	23.81±10.2
Mean hemoglobin level	7.3±1.8
Median duration of CKD	2 (0.2-5) years
Mean BMI	17.84±7.9

ESRD=End stage renal disease, CKD=Chronic kidney disease, DM=Diabetes mellitus, BMI=Body mass index

Regarding etiology of CKD in the patients, 35 (43.8%) had chronic glomerulonephritis, 29 (36.2%) patients had hypertension only, 9 (11.2%) had type -2 DM only, 6 (7.6%) had hypertension and diabetes and 1 (1.2%) patient had unidentified etiology [Table 1].

Considering test of psychomotor speed, median score of cognitive performance was significantly (P < 0.0001) prolonged in ESRD patients compared to control on dominant auditory reaction time (350.8 vs. 196.9 ms), nondominant auditory reaction times (375.9 vs. 204.6 ms), dominant visual reaction time (284.1 vs. 133.4 ms), nondominant auditory reaction times (310.0 vs. 141.9 ms) [Figure 1]. For test of memory; RMT was significantly (P < 0.0001) prolonged in ESRD patient than control as mean response time on visual RMT in ESRD in cases and control were 71.8 ± 16.8 ms and 53.9 ± 14.3 ms, respectively, and on word RMT in ESRD and cases were 51.4 ± 19.0 ms and 35.8 ± 14.3 ms, respectively. With the CVST which can distinguish brain damage from normal brain; mean response time was significantly (P < 0.0001) prolonged in ESRD patient than controls (14.23 ± 3.9 vs. 6.95 ± 1.5 respectively).

Figure 1

Cognitive performance on: Auditory reaction test (a) dominant (b) nondominant, visual reaction time test (c) dominant (d) nondominant in end-stage renal disease and matched control

On assessment of attention, concentration and psychomotor speed with BCT, binary choice accuracy was lower in ESRD patients (57.94 ± 17.2) than in controls (71.07 ± 12.3), P < 0.05.

The mean finger tapping scores in ESRD patients and controls were 32.52 ± 18.8 and 58.17 ± 12.4 respectively in the dominant hand, and 31.2 ± 19.0 and 61.1 ± 12.3 respectively in the nondominant hand. P < 0.05 was considered statistically significant in each case [Figure 2].

Figure 2

Cognitive performance on: (a) computer assisted visual task (b) binary choice task, finger tapping task (c) non-dominant (d) dominant in ESRD and matched control

Discussion

In the present study, we found a significant difference across all the cognitive domains assessed in ESRD patients in comparison with age, sex and level of education-matched control. This finding is in conformity with reports from other workers.[10171819]

Cognitive involvement and dementia are commonly seen in patients with CKD, particularly in subjects with advanced stage disease, but are poorly recognized by nephrologists.[20] Previous studies[111718] reported a close association between CKD and cognitive impairment. In a study, the prevalence of mental impairment was as high as 30% among persons with kidney failure.[3] A systematic review estimated that as many as 60% of dialysis patients may meet diagnostic criteria for cognitive dysfunction.[21]

We found in this study that ESRD patients performed significantly worse than controls on memory tests. This finding is compatible with previous reports.[1016] Our observation suggests that ESRD patients may be at higher risk of memory impairment than the general population. Similarly, there was demonstrable reduced performance in attention, concentration, visual processing speed, motor activation and fluency and psychomotor performance in ESRD patients. These findings are in agreement with reports from other studies.[2223] However, relative reduction in attention and concentration seen in the current study is in contrast with the finding of Egbi et al.[10] This difference may not be unconnected with methodological differences. Cognitive symptoms appear to represent one of the core features of depressive disorders with an impact on many functional outcomes;[2425] thus, deliberate effort was made in the present study to exclude depression and severe functional disability in the study patients.

Although this study was not designed to evaluate the relationship between cognitive performance and glomerular filtration rate as the focus of our study was ESRD, other studies have shown a graded association between CKD and cognitive impairment with different cognitive screening instruments, such as the six-item cognitive screening test derived from the widely used MMSE.[11116] Other neuropsychological detecting for detecting impaired cognitive function in specific domains suggest that even small reductions in kidney function are associated with clinically significant consequences for cognitive functioning.[1718]

Cognitive dysfunctions in CKD patients have implication for therapy and quality of life. For instance, cognitive impairment in ESRD patients that is severe enough to preclude reliable compliance is an established contraindication to kidney transplantation.[26] However, there is clear evidence that cognitive performance improves following renal transplantation; Griva et al. reported a remarkable improvement in cognitive functions compared to baseline values 6 months after transplantation.[22]

The mechanism underlying cognitive impairment in persons with ESRD is largely unknown. The mechanisms proposed as mediators of relations between kidney function and cognition are similar to those that have been advanced to explain relations between other risk factors for cardiovascular disease and cognition.[16] Body of evidence suggests that cerebrovascular disease may play a prominent role in the neuropathology of cognitive dysfunction in ESRD. The vascular beds of the brain and kidney have similar anatomic and hemodynamic features. Consequently, cognitive impairment in ESRD or CKD may be a reflection of vascular injury in end organs.[20] This relationship is further corroborated by neuroimaging studies which revealed a large vessel stroke, small vessel stroke, and white matter lesions.[2728]

Given that cognitive impairment is associated with high risks of death, dialysis withdrawal, hospitalization, and disability among patients with ESRD, recognizing and effectively managing cognitive impairment may improve the care of persons with ESRD. Periodic screening is, therefore, needed to accurately identify patients with cognitive impairment to improve their care and quality of life. Screening for cognitive dysfunctions in persons with ESRD could begin with questioning of the caregivers as caregivers often notice cognitive deficits before they are apparent to clinicians, and their observations or the availability of a pre-ESRD cognitive assessment is useful for helping to establish the course of impairment. Preventive measure focusing on vascular risk factor modification, physical and cognitive activity, that have shown some promise in the general population, may be reasonably extended to the ESRD patients.

In spite of our findings, the current study has some limitations, the control, unlike ESRD patients, did not have extensive hematological and biochemical evaluations, thus, they might not have been perfect control. Nonetheless, the control was strictly matched in the areas known to influence cognitive functions i.e., age, sex and level of education.

Conclusion

This study showed a significant difference across all the cognitive domains assessed in ESRD patients in comparison with age, sex and level of education-matched controls. Our data further emphasize the need to assess CKD patients for cognitive impairment to improve their care and quality of life.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.