| Abstract|| |
Cognitive dysfunction includes reduced mental alertness, intellectual impairment, decreased attention and concentration, memory deficits and diminished perceptual-motor coordination. Chronic kidney disease (CKD) patients may suffer from cognitive impairment, which may decrease an individual's quality of life, increase resource utilization and result in suboptimal medical care. This study was carried out on 120 patients with different stages of CKD from our nephrology outpatient clinic divided into three groups: Group I: 50 CKD patients, stage 3 and stage 4; Group II: 50 end-stage renal disease patients on regular hemodialysis with K t/v >1.1; and Group III: 20 acute kidney injury patients, followed-up till their renal functions stabilized besides Group IV: 20 healthy subjects served as controls. All patients underwent laboratory investigations and psychometric tests, which include trial making test part B, digit span test, digit symbol test and mini-mental state examination. There was a significant difference of mean values of cognitive function tests in Groups I, II and III on comparing them with Group IV. Stage 3 CKD scored better than stage 4 CKD, which was worse than hemodialysis patients, and lastly acute kidney injury patients had mild cognitive impairment, which was restored after recovery. We found an association between hemoglobin and cognitive function tests score in the studied groups. The degree of cognitive impairment was associated with the severity of CKD, and dialysis improved cognitive performance.
|How to cite this article:|
Nasser ME, Shawki S, El Shahawy Y, Sany D. Assessment of cognitive dysfunction in kidney disease. Saudi J Kidney Dis Transpl 2012;23:1208-14
|How to cite this URL:|
Nasser ME, Shawki S, El Shahawy Y, Sany D. Assessment of cognitive dysfunction in kidney disease. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2013 May 24];23:1208-14. Available from: http://www.sjkdt.org/text.asp?2012/23/6/1208/103561
| Introduction|| |
Cognition is the mental process of acquiring knowledge by the use of reasoning or perception, and underlies all daily activities, from the most basic to the most complex.  Cognitive dysfunction includes reduced mental alertness, intellectual impairment, decreased attention and concentration, memory deficits and diminished perceptual-motor coordination.  Cognitive impairment is associated with an increased risk of death in dialysis patients, which is mostly due to cerebrovascular disease and prevalence of traditional and non-traditional vascular risk factors in chronic kidney disease (CKD). 
The severity of CKD is associated with the severity of cognitive impairment, independent of age, education and other key confounders.  Cognitive impairment in patients with CKD may also be mediated by the retention of putative neurotoxins, including products of nitrogen metabolism and parathyroid hormone. Furthermore, chronic inflammation is a risk factor for development of cognitive impairment. 
It is important to identify those patients with cognitive impairment to reduce the considerable morbidity associated with this condition and improve their quality of life.  There is improvement in short-term memory after starting maintenance hemodialysis. However, cognitive dysfunction, including reduced concentration capacity, learning and memory as well as cognitive inflexibility and impaired complex novel problem solving, is commonly reported to persist in dialysis patients.  Some absolute levels of cognitive function, particularly the attention and concentration test scores, were found to be associated with the adequacy of dialysis. 
Two broad classes of tests are used to assess cognitive function in the general population. Neurophysiological testing uses imaging techniques and electrophysiology to evaluate structural and functional abnormalities, and uses validated questions and screening tests. 
Our study aims to assess the cognitive function in CKD and acute kidney injury (AKI), and correlation with various clinical and laboratory parameters. In addition, we evaluate the changes in the cognitive function following dialysis treatment.
| Materials and Methods|| |
We studied 120 patients with different stages of CKD, and divided them into four groups: Group I: included 50 CKD patients, 28 of them with stage 3 and 22 with stage 4, selected from our nephrology outpatient clinic at Ain Shams University Hospital; Group II: included 50 patients on regular hemodialysis thrice weekly (4 h each session) with K t/v >1.1; Group III: included 20 AKI patients, who were followed-up till recovery of renal function; and Group IV: included 20 healthy subjects matched with patients as regards age, sex and education.
We excluded from the study patients with evident cerebrovascular disease, thyroid disease, severe anemia, uncontrolled hypertension, malnutrition, major psychiatric illness, major visual or hearing impairment, unstable coronary heart disease, collagen vascular disease and vasculitis. All the medications were revised to exclude any drugs that might have an effect on the cognitive function.0
We obtained history, clinical examination and laboratory investigations from all the patients. Psychometric tests were done on the dialysis off day, which included a trial of making test part B (TMT-B), which requires that the subject connects with lines in a given sequence circled digits and letters randomly distributed on a page as shown in [Figure 1]. The prescribed sequence is from 1 to A to 2 to B to 3 to C, etc., and performance is scored in terms of time to complete the task correctly. The TMT-B assesses attention, visual scanning, psychomotor speed and ability to sequence to shift the cognitive set. 
The digit span (D-span) psychometric test is a widely used auditory verbal short-term (working) memory test. It requires the subject to repeat a spoken string of digits, two trials each, for stings three to nine digits in the forward order and two to eight digits in the reverse order. The score is the number of correct trials.
The psychometric D-symbol test evaluates the sustained attention, visual searching, visual sequencing and new learning abilities of the patients. Subjects are given nine different symbols that are matched to numbers and are required to change the number with its matched symbol as shown in [Figure 2]. The score of the test is the number of symbols changed correctly within 90 s.  The psychometric mini-mental state examination as shown in [Table 1] is a widely used well-validated screening tool for cognitive impairment. It tests five areas of cognitive function; the first area includes orientation, which is assessed by asking the usual questions about time, day, date and location; the second area includes registration, which is actually a short-term memory test where the subject must recall three objects named by the examiner; the third and fourth area include attention and calculation, which are measured by having the subject begin with the number 100 and count backwards by seven (serial 7s); then, recall by which the subject must recall the three objects named previously.
Finally, language functions are assessed by having the subject name simple objects, repeat a sentence and follow a three-stage command. A constructional task is also included in the language section where the subject must copy overlapping pentagons.
Each discrete subtask completed correctly earns one point toward a maximum score of 30. The mild cognitive impairment score ranges between 26 and 28, moderate cognitive impairment score between 18 and 25 and severe impairment below 18. 
| Statistical Analysis|| |
The statistical analysis of data was performed by using excel program and the statistical package for social science (SPSS) program version 10. The description of the data done was written in the form of the mean (±) SD for quantitative data. The analysis of the data was done to test statistically significant difference between groups, where P-value less than 0.05 was considered as significant. For quantitative data, Student's t-test was used to compare the two groups and paired sample t-test was used to compare one group at different measurements. One way analysis of variance (ANOVA) test with post hoc analysis was used to compare more than two groups. To test the association between variables, Pearson correlation co-efficiency test was used.
| Results|| |
This study included 120 patients; 53.6% males and 46.4% females, with a median age of 45 years and a range from 22 to 60 years, and the mean of the education period was 8.14 ± 3.5 years. There were no significant differences in the gender, median age and education years among the different study groups or controls. The etiology of end-stage renal disease (ESRD) in the participating subjects is shown in [Figure 3], and the etiology of AKI in the participating subjects is shown in [Figure 4].
[Table 2] shows that there were highly significant differences between the mean values of the cognitive function tests of Groups I, II and III as compared with Group IV (control group), indicating that uremia had a major influence on the cognitive function in CKD patients. In accordance, we found that cognitive function in stage III was worse than that in stage 4, indicating that cognitive function deteriorates with progress-sion of kidney disease.
|Table 2: Comparison of the scores (mean ± SD) of the cognitive function tests among the four groups.|
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[Table 2] and [Table 3] show that dialysis improved the cognitive function as patients under regular efficient hemodialysis for more than one year performed better in the evaluation tests of cognitive function than the pre-dialysis patients with stage 3 and stage 4 CKD. [Table 4] shows that the cognitive function in stage III was worse than that in stage 4, indicating that cognitive function deteriorates with progression of kidney disease.
|Table 4: Comparison between mean values of cognitive function tests of stage III and IV CKD.|
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[Table 2] and [Table 3] also show that patients with AKI had mild degree of cognitive dysfunction in comparison with CKD and hemodialysis patients. In addition, cognitive impairment was corrected within the recovery of kidney function as shown in [Table 5].
There was a significantly positive correlation between the means of the hemoglobin levels and cognitive function tests score in pre-dialysis, hemodialysis and AKI patients [Table 6]. In contrast, there was no correlation between dialysis duration and cognitive function tests score.
|Table 6: Pearson correlation of hemoglobin with cognitive function tests in the studied groups.|
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| Discussion|| |
Cognitive impairment is a well-recognized manifestation of uremia. This is characterized by quiet stupor, dullness of intellect, sluggishness of manner and drowsiness.  The severity of the cognitive impairment correlates with the severity of CKD, independent of age, education and other key confounders. The prevalence of global cognitive impairment in persons with CKD is more than twice that of the age-matched general population, as shown in our study, and it was not explained by commonly measured metabolic alterations associated with CKD.  However, the cognitive status improves following initiation of dialysis in comparison with the untreated advanced CKD patients, as shown in our study.  Cognitive impairment also improves with renal transplantation.  Nevertheless, up to 70% of hemodialysis patients aged 55 years and older have moderate to severe chronic cognitive impairment, yet it is largely undiagnosed.  Conventional hemodialysis may induce recurrent episodes of acute cerebral ischemia, which, in turn, may contribute to acute decline in cognitive function during dialysis. Thus, the worst time to communicate with dialysis patients may be during the hemodialysis session. Both symptomatic and occult, subclinical ischemic cerebrovascular disease appears to play a large role in a proposed model of accelerated vascular cognitive impairment in these populations. Severe cognitive impairment among hemodialysis patients is associated with an approximately two-fold increased risk of both mortality and dialysis withdrawal. Therefore, awareness of cognitive function in dialysis patients improve quality of care and outcomes by raising clinicians' awareness of the potential effects of cognitive impairment on medication, fluid and dietary compliance. 
In our study, there was a highly significant difference between CKD stage 5 patients on HD and control groups in the mean values of cognitive function tests score. This was in agreement with the results of other studies. , Furthermore, there were highly significant differences between stages 3 and 4 CKD and ESRD patients on hemodialysis in the mean values of cognitive function tests score; these results were in agreement with the results of other reports. ,,
In our study, there was a significant correlation between hemoglobin levels and cognitive function tests in CKD, ESRD and AKI patients, and this was in agreement with the studies of other investigators. ,,,
In our study, we found mild impairment in cognitive function in AKI in comparison with CKD and ESRD, with significant improvement in cognitive performance after recovery, which may be due to uremic toxins and/or hypoperfusion of the brain tissue that accompanies hypovolemia that occurs frequently with AKI. Further studies are needed to investigate the role of hypovolemia in cognitive dysfunction.
In conclusion, we found, in our study, significant differences of cognitive function tests results in CKD 3, 4, 5 and AKI patients, and that the severity of cognitive impairment was associated with the severity of the kidney disease, which improved with dialysis. Finally, cognitive performance was affected by hemoglobin level, suggesting that treatment of anemia in CKD patients may improve cognitive performance.
| References|| |
|1.||Teri L, McCurry SM, Logsdon RG. Memory, thinking and aging. What we know about what we know. West J Med 1997;167:269-75. |
|2.||Pliskin NH, Yurk HM, Ho LT. Neurocognitive function in chronic hemodialysis patients. Kidney Int 1996;49:1435-40. |
|3.||Kurella M, Chertow GM, Luan J, Yaffe K. Cognitive impairment in chronic kidney disease. J Am Geriatric Soc 2004;52:1863-9. |
|4.||Madero M, Gul A, Sarnak MJ. Cognitive function in chronic kidney disease. Semin Dial 2008;21:29-37. |
|5.||Kurella M, Yaffe K, Shlipak MG, Wenger NK, Chertow GM. Chronic kidney disease and cognitive impairment in menopausal women. Am J Kidney Dis 2005;45:66-76. |
|6.||Luan J, Kurella M, Yaffe K. Validation of the kidney disease quality of life (KDQOL) cognitive function subscale. Kidney Int 2004; 66:2361-7. |
|7.||Pliskin NH, Yurk HM, Ho LT. Neurocognitive function in chronic hemodialysis patients. Kidney Int 1996;49:1435-40. |
|8.||Griva K, Newman SP, Hankin's M. Acute neuropsychological changes in hemodialysis and peritoneal dialysis patients. Health Psychol 2003;22:570-8. |
|9.||Pereira AA, Weiner DE, Scott T. Cognitive function in dialysis patients. Am J Kidney Dis 2005;45:448-62. |
|10.||Marsh JT, Brown WS, Wolcott D. rHuEPO treatment improves brain and cognitive function of anemic dialysis patients. Kidney Int 1991;39:155-63. |
|11.||Lee SY, Lee HJ, Kim YK, et al. Neurocog-nitive function and quality of life in relation to hematocrit levels in chronic hemodialysis patients. J Psychosom Res 2004;57:5-10. |
|12.||Crum RM, Anthony JC, Bassett SS, Folstein MF. Population based norms for the MiniMental State examination by age and educational level. JAMA 1993;269:2386-91. |
|13.||Kurella M, Chertow GM, Luan J, Yaffe K. Cognitive impairment in chronic kidney disease. J Am Geriatric Soc 2004;52:1863-9. |
|14.||Krishnan AV, Kiernan MC. Neurological complications of chronic kidney disease. Nat Rev Neurol 2009;5:542-51. |
|15.||Murray AM. Cognitive impairment in the aging dialysis and chronic kidney disease populations: an occult burden. Adv Chronic Kidney Dis 2008;15:123-32. |
|16.||Fazekas G, Fazekas F, Schmidt R. Brain MRI findings and cognitive impairment in patients undergoing chronic hemodialysis treatment. J Neurol Sci 1995;134:83-8. |
|17.||Sehgal AR, Grey SF, DeOreo PB, Whitehouse PJ . Prevalence, recognition, and implications of mental impairment among hemodialysis patients. Am J Kidney Dis 1997;30:41-9. |
|18.||Khatri M, Nickolas T, Moon YP, et al. CKD associates with cognitive decline. J Am Soc Nephrol 2009;20:2427-32. |
|19.||Etgen T, Sander D, Chonchol M, et al. Chronic kidney disease is associated with incident cognitive impairment in the elderly: The INVADE study. Nephrol Dial Transplant 2009;24:3144-50. |
|20.||Khatri M, Nickolas T, Moon YP, et al. CKD Associates with Cognitive Decline. J Am Soc Nephrol 2009;20:2427-32. |
|21.||Marsh JT, Brown WS, Wolcott D. rHuEPO treatment improves brain and cognitive function of anemic dialysis patients. Kidney Int 1991;39:155-63. |
|22.||Brickman AL, Yount SE, Blaney NT, Rothberg S, De-Nour AK. Pathogenesis of cognitive complaints in patients on hemodialysis. Gen Hosp Psychiatry 1996;18:36-43. |
|23.||Madan P, Kalra OP, Agarwal S, Tandon OP. Cognitive impairment in chronic kidney disease. Nephrol Dial Transplant 2007;22:440-4. |
Division of Nephrology, Ain-Shams University, Cairo
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]