|Year : 2012 | Volume
| Issue : 4 | Page : 222-229
Cognitive functions in patients with liver cirrhosis: Assessment using community screening interview for dementia
Olusegun Adekanle1, Taofiki A Sunmonu2, Morenikeji A Komolafe1, Dennis A Ndububa1
1 Department of Medicine, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State, Nigeria
2 Department of Medicine, Federal Medical Centre, Owo, Ondo State, Nigeria
|Date of Web Publication||24-Oct-2012|
Taofiki A Sunmonu
Department of Medicine, Federal Medical Centre, Owo, Ondo state
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: Neurocognitive dysfunction is common in patients with liver cirrhosis who have no evidence of overt hepatic encephalopathy and is usually associated with impairment of activities of daily living in the patients.
Materials and Methods: Forty patients with liver cirrhosis without overt hepatic encephalopathy were studied along with forty-one healthy controls. Blood samples were taken from the patients for liver function tests and Hepatitis B and C screening. Liver disease severity was graded using the Child-Pugh scoring system. Community Screening Interview for the Dementia (CSID) questionnaire was administered to all subjects. The CSID questionnaire assesses the cognitive functions of the subjects in the domains of language, memory, orientation, attention/calculation, and praxis. The data were collated and analyzed with the aid of SPSS 15.0 software for frequency, means, and comparison of means using Student's t-test and one-way ANOVA. Significant level was put at P< 0.05.
Results: The mean age ± SD of the patients was 46.15±15.31 years and the controls was 45.66±11.54 years. There were 30 males and 10 females in the patients group while the control had has 26 males and 15 females. Majority of the patients had secondary level of education. Nine out of 40 patients (23%) had abnormally low total CSID score. The patients with liver cirrhosis performed poorly in the domains of language, memory, attention/calculation, and praxis. There was no difference in the orientation scores between the patients and the normal controls. The type of Hepatitis virus infection, serum liver enzyme, serum albumin, serum bilirubin, prothrombin time and Child Pugh class of the patients did not influence cognitive performance in the patients.
Conclusion: Patients with liver cirrhosis have significant cognitive impairment compared with controls and liver function tests/ clinical parameters in the patients did not correlate with their cognitive functions.
| Abstract in French|| |
Contexte: Neurocognitive dysfonctionnement est fréquente chez les patients avec cirrhose du foie qui n'ont aucune preuve manifeste encéphalopathie hépatique et est généralement associé à l'atteinte des activités de la vie quotidienne chez les patients atteints de.
Matériaux et procédés: Quarante patients atteints de cirrhose du foie sans encéphalopathie hépatique manifeste ont été étudiés ainsi que quarante et un témoins sains. Des échantillons de sang ont été prélevés les patients pour les tests de la fonction hépatique et le dépistage de l'hépatite b et C. Gravité de la maladie hépatique a été classée à l'aide de l'enfant-Pugh, système de notation. Entrevue de dépistage communautaire pour le questionnaire de démence (CSID) a été administré à tous les sujets. Le questionnaire CSID évalue les fonctions cognitives des sujets dans les domaines de la langue, la mémoire, l'orientation, l'attention et calcul et praxis. Les données ont été compilées et analysées à l'aide du logiciel SPSS 15,0 pour la fréquence, des moyens et la comparaison des moyens en utilisant le test t et ANOVA à sens unique de l'étudiant. Niveau important fut mis au p< 0,05.
Résultats: L'âge moyen ± SD des patients a été 46.16 ± 15.31 années et les contrôles a 45.66 ± 11.54 ans. Il y a 30 mâles et 10 femelles dans le groupe les patients alors que le contrôle a eu 15 femelles et mâles a 26. La majorité des patients avait un niveau secondaire de l'éducation. Neuf des 40 patients (23%) avaient anormalement faible score CSID. Les patients atteints de cirrhose du foie mal effectué dans les domaines de la langue, la mémoire, l'attention et calcul et praxis. Il n'y n'avait aucune différence dans les notes d'orientation entre les patients et les témoins normaux. Le type d'hépatite infection par le virus, enzyme sérique foie, albumine, bilirubine sérique, temps de prothrombine et Child Pugh classe des patients n'influence pas la performance cognitive chez les patients.
Conclusion: Patients atteints de cirrhose du foie ont des troubles cognitifs importants comparativement aux contrôles et tests de fonction hépatique / paramètres cliniques chez les patients ne pas en corrélation avec leurs fonctions cognitives.
Mots clés: Fonctions cognitives, l'encéphalopathie hépatique, cirrhose du foie
Keywords: Cognitive functions, hepatic encephalopathy, liver cirrhosis
|How to cite this article:|
Adekanle O, Sunmonu TA, Komolafe MA, Ndububa DA. Cognitive functions in patients with liver cirrhosis: Assessment using community screening interview for dementia. Ann Afr Med 2012;11:222-9
|How to cite this URL:|
Adekanle O, Sunmonu TA, Komolafe MA, Ndububa DA. Cognitive functions in patients with liver cirrhosis: Assessment using community screening interview for dementia. Ann Afr Med [serial online] 2012 [cited 2020 Oct 24];11:222-9. Available from: https://www.annalsafrmed.org/text.asp?2012/11/4/222/102853
| Introduction|| |
Minimal hepatic encephalopathy (MHE) is a neurocognitive dysfunction which occurs in cirrhotic patients that is characterized by a number of quantifiable neuropsychological deficits and yet patients have a normal mental and neurological status on global examination. , The global prevalence of MHE ranges from 30% to 80% in patients with liver cirrhosis. , The current proposed mechanism for hepatic encephalopathy includes the accumulation of neurotoxins such as ammonia.  and other nitrogenous waste products such as Gamma Amino-butyric acid which may accumulate in the body and achieve toxic levels in the central nervous system.  The presence of increased tissue levels of false neurotransmitters within the brain.  elevated CNS glutamate and glutamine levels.  and elevation of putative endogenous CNS benzodiazepines have been reported as pathophysiological mechanisms underlying the development of MHE in liver cirrhosis patients.
Abnormalities of neurophysiological and neuroimaging parameters have been documented in patients with cognitive dysfunctions while abnormalities of the electroencephalogram (EEG) were reported in some patients with liver cirrhosis without overt encephalopathy. , Brain stem auditory evoked potential response abnormalities have been documented in MHE and recently Saxena et al.  showed increased P300 wave latency in patients with chronic liver disease. Abnormal changes were also observed on magnetic resonance imaging of the brain which showed brain oedema, cortical atrophy, hyperintensity of globus pallidus and other subcortical nuclei. 
The cognitive dysfunctions in patients with liver cirrhosis without overt encephalopathy is characterized by deficit in attention, vigilance, memory and orientation.  MHE also causes disorders of sleep and sleep wake cycle.  Several studies have demonstrated impaired health related quality of life in cirrhotic patients with neurocognitive dysfunctions. , The cognitive impairment also affects the ability to perform complex tasks such as driving, operation of machinery and other work-related activities. , MHE may also affect patient socio-economic status by interfering with work performance.  Schomerus and Hamster in 2001.  showed that working and earning capacity are reduced in cirrhotic patients with cognitive dysfunctions. The presence of neurocognitive dysfunctions predicts not only development of overt hepatic encephalopathy but also premature death. , There is paucity of literature on neurocognitive functions in liver cirrhosis patients without hepatic encephalopathy in sub-Saharan Africa and hence the need for this study.
| Materials and Methods|| |
This is a cross sectional study in which.  patients with liver cirrhosis without overt hepatic encephalopathy were studied along with.  normal controls at the gastroenterology clinic of the Federal Medical Centre, Owo, Ondo State, Nigeria and Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria between June 2008 and August 2010. The ethical committee of the Federal Medical Centre, Owo gave approval for the study and informed consents were obtained from the patients and normal control subjects. The normal controls were recruited from the members of staff of the hospital and patients attending the hospital medical outpatient clinic who did not have risk factors for cognitive dysfunctions. The Inclusion criteria were age equal to or greater than 16 years, liver cirrhosis as diagnosed by clinical, ultra-sonographic, biochemical and histological criteria. Patient must not have overt hepatic encephalopathy (West Heavens grade 0) The exclusion criteria were age lesser than 16 years, presence of overt hepatic encephalopathy, presence of other medical illness / psychiatric illnesses such as diabetes mellitus, hypertension, hypothyroidism, hypovitaminosis, epilepsy, depression, and dementia. The participants who use psychotropic drugs or engaged in drug abuse were also excluded Applicable exclusion criteria were used in the selection of normal control subjects for the study. A questionnaire was developed and applied to all subjects. Emphasis was placed on socio demographic data, history of symptoms and risk factors for liver cirrhosis. General physical and neurological examinations were performed on all subjects.
Blood samples were taken from the patients for liver function tests that assessed two functions; the liver enzymes such as Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Alkaline phosphatase; these assess the hepatic injury while serum albumin, prothrombin time ratio (PTR) assess hepatic synthetic function. Liver ultrasound scan was done for all patients. Liver biopsy was done for the patients without contraindications and histological classification of the degree of liver fibrosis was done using the KNODELL criteria. The patient's liver disease severity was graded using the Child-Pugh scoring system.  The Community Screening Interview for Dementia (CSID) adapted for Nigerians which had been used in several studies in Nigeria. , was used to assess the participants. Though the CSID has not been used previously in the evaluation of cognitive function in patients with liver cirrhosis but it is a simple, cheap, readily available "Paper and Pen" instrument that assesses the following cognitive domains: language (tasks assessing naming, comprehension, motor response, naming fluency, definition, and repetition), memory (tasks assessing recall, registration, and remote memory), attention and calculation, orientation (to place and time), and praxis (copying). The CSID had been shown to have impressive screening quality for detection of cognitive dysfunction in some patients in a Nigerian study. 
Differences in demographic details (age, sex, and level of education) between patients with liver cirrhosis and controls were compared using the X 2 test. Mean scores of the various CSID subscales of the liver cirrhosis patients were compared with controls using Student t-test. The impact of clinical/laboratory variables on cognitive performance in liver cirrhosis patients was analyzed using Student t-test and One way Analysis of Variance (ANOVA) as appropriate and this generate F value, t value and P value. P<0.05 was taken as being significant.
| Results|| |
Sociodemographic details of subjects
There were 40 patients with liver cirrhosis and 41 normal healthy controls in the study. These were 30 males and 10 females in the liver cirrhosis group while there were 26 males and 15 females in the control group. The mean (SD) age of patients with liver cirrhosis in years was 46.15 ± 15.31 while that of the controls was 45.66 ± 11.54 years. The other details of the socio-demographic details were as highlighted in [Table 1].
Comparison of cognitive function between patients with liver cirrhosis and controls using the CSID
The liver cirrhosis patients scored lower than the normal controls in the domains of language, memory, attention/calculation, praxis, and total CSID score (P < 0.05); however there was no difference in the score on orientation between the patients with liver cirrhosis and normal controls (P >0.05). This is as highlighted in [Table 2]. Nine out of the 40 patients with liver cirrhosis had abnormally low total CSID score i.e. < mean total CSID score minus 2 standard deviation of the control (63.0), while none of the controls scored below this value.
|Table 2: Comparison of cognitive function between patients with liver cirrhosis and normal controls using CSID|
Click here to view
The impact of laboratory/clinical variables on cognitive functions in liver cirrhosis patients is as highlighted in [Table 3] a and b.
Viral serological markers . The hepatitis B surface antigen (HBsAg) positive patients performed slightly better on all the various subtests of the CSID and the total CSID scores when compared to HBsAg negative patients, but this did not reach statistical significance (P>0.05). The antihepatitis C virus antibody (anti-HCV) positive patients performed better in the domains of language and memory than the anti-HCV negative patients, but this did not reach statistical significance (P>0.05). However, the performance of anti-HCV negative patients was better on attention/calculation, praxis, and the total CSID score when compared to the anti-HCV positive patients, but this did not reach statistical significance (P>0.05). The performance on the orientation subscale was statistically better among the anti-HCV negative patients when compared to HCV positive patients (P<0.05).
Serum aspartate aminotransferase test (AST): The patients with AST level in the normal range had marginally lower scores in the domains of the language, attention, and praxis than the controls but this did not reach statistical significance. The scores on memory and total CSID score were also not affected significantly by the level of AST.
Serum alanine aminotransferase test (ALT): The patients with moderately elevated ALT level performed better on the memory, orientation, attention\calculation, praxis, and total CSID score when compared to the patients with ALT in the normal range, but this did not reach statistical significance.
Alkaline phosphatase (ALP) test: The performance on the memory orientation, attention/calculation, and total CSID scale was better with increasing ALP levels, but this did not reach statistical significance; there was also no statistically significant difference in performance on language and praxis scale among the patients with normal, moderately, and severely elevated ALP levels.
The performances on memory, orientation, attention\calculation subscales became better with increasing serum albumin levels, but this did not reach statistical significance (P>0.05). There was also no statistical difference in language, praxis, and total CSID score among the patients with normal, or abnormally low serum albumin levels (P>0.05).
Total bilirubin : There was no significant importance of serum bilirubin levels on the performance on language, memory, orientation, attention\calculation, praxis, and total CSID score in the patients with liver cirrhosis.
Patients in Child-Pugh class A performed better than patients in Child-Pugh classes B and C on memory, orientation attention\calculation, and total CSID scores, but this did not reach statistical significance (P>0.05). There were also no statistically significant differences in performance among the Child-Pugh classes on language and praxis scales (P>0.05).
Prothrombin time ratio
Patients with normal prothrombin time ratio (PTR) had higher scores in performances in the domains of language, memory, orientation, attention/calculation, and praxis. Total CSID scores became poorer with prolonged prothrombin time ratio; however this did not reach statistical significance (P>0.05).
| Discussion|| |
Previous studies demonstrated that patients with liver cirrhosis with minimal hepatic encephalopathy exhibited poor performance on neuropsychological examinations when compared with normal control subjects. ,,, The cognitive dysfunctions include poor psychomotor function, attention/concentration impairment, memory impairment, and language abnormalities. ,, In this study, the patients with liver cirrhosis performed poorly when compared to controls in the domains of language, memory, attention/calculation, and praxis, but there was no difference in the performances on the orientation scale between the patients with liver cirrhosis and normal control subjects. The prevalence of cognitive dysfunction in the patients with liver cirrhosis without overt hepatic encephalopathy in this study was 23%.
Memory impairment have been documented in patients with MHE,  and in these studies verbal memory, visual memory, and complex memory processes were affected and this is in agreement with this study in which memory performance in the patients with liver cirrhosis was worse than control subjects. This finding is in keeping with the findings of Bahceci et al. where a 36-92% decrement in various memory scores was found in cirrhotic patients when compared to healthy controls. Some other authors have been able to demonstrate working memory deficit in cirrhotic patients.  However some workers were of the opinion that short- and long-term memory are relatively spared in cirrhotic patients who did not have clinical evidence of hepatic encephalopathy. , The markers of hepatic injury (liver enzymes) and hepatic synthetic function (serum albumin and Prothrombin time ratio) had no influence on memory performance in the patients in this study. A study showed that in MHE patients, memory abnormalities correlated with liver function impairment,  while another study showed that biochemical markers of hepatic injury and hepatic synthetic function had no influence on memory functions.  The findings from this study showed that memory impairment did not correlate with liver function tests' derangement. Several studies have shown that the severity of liver disease (as assessed by Child-Pugh scores) had no impact on memory function; ,,, however some studies reported a correlation between the severity of liver disease and memory scores, , but in this study the severity of liver disease had no impact on memory function in the patients. The patients with hepatitis C virus infection are known to have poor cognitive performances including memory tasks,  but in this study there was no difference in cognitive performances between the hepatitis B virus and hepatitis C virus infected patients probably because the number of hepatitis C virus infected patients in the study is small which represents only 5% of the patients in this study.
Various studies have shown that the language is relatively spared in cirrhotic patients with MHE, , while some other studies showed that language functions were impaired in patients with MHE; , however in this study, language function is impaired in the patients with liver cirrhosis relative to healthy controls. In this study the liver function tests and the extent of liver disease severity and the type of hepatitis virus infection did not influence the language function of the patients. A previous study showed that theb impaired hepatic protein synthetic factor (as assessed by serum albumin and Prothrombin ratio) correlated negatively with language efficiency, while hepatic injury factors (serum ALT, AST, alkaline phosphatase) did not correlate with any of the neuropsychological dimensions in MHE patients. 
Attention and concentration were frequently impaired in cirrhotic patients without overt hepatic encephalopathy, ,,, but a study with a small sample size showed normal attention abilities in patients with liver cirrhosis without overt hepatic encephalopathy.  This study corroborated the former studies as the patients with liver cirrhosis scored lower on the attention/concentration scales relative to the healthy control subjects. In this study, the attention of patients was not influenced by the extent of hepatic injury, hepatic synthetic dysfunction, disease severity or the type of hepatitis virus infection. The impact of liver function tests on attention abilities in MHE patients is poorly known. The deleterious effect of hepatitis C virus infection on cognitive functions in patients with MHE had been documented in previous studies, , but this study showed no significant difference in cognitive performances of both the hepatitis B and hepatitis C infected patients probably because only a small proportion of the patients (5%) had hepatitis C infection. Also the severity of liver disease correlated with cognitive performance including attention tasks in patients with liver cirrhosis with MHE in some studies. , In the studies by Bahceci et al.  and Fontana et al.  the liver disease severity as assessed by the Child-Pugh scores did not correlate with performance on attention and concentration scales. In this study, the Child-Pugh classes of the patients did not correlate with their attention performance.
In overt hepatic encephalopathy, orientation of the patients is usually impaired. In patients with minimal hepatic encephalopathy, impairment of orientation tasks have been noted.  In this study, there was no difference in the orientation scores between the patients with liver cirrhosis and normal control subjects probably because the study sample size was small and probably again a different cognitive tool was employed in this study. The impact of liver function tests, disease severity, and type of hepatitis virus infection on orientation functions in the liver cirrhosis patients is poorly known, but in this study these variables had no impact on orientation task performance of the patients.
Abnormalities of praxis do occur in cirrhotic patients with MHE, ,,, and this is in keeping with the findings from this study where the patients with liver cirrhosis performed very poorly compared with the controls on praxis scale. Some other studies reported preserved visuo-spatial skills in some patients with MHE.  The patients variables that may influence visuo-practic abnormalities in the MHE patients include impaired nitrogen processing abilities of the liver which include blood urea nitrogen and blood ammonia while abnormalities of hepatic injury and hepatic protein synthesis showed no correlation with visuo-practic skills in patients with liver cirrhosis with MHE,  and these were in keeping with the findings from this study where indices of hepatic injury (increase in liver enzymes) and indices of hepatic synthetic function (serum albumin, prothrombin time ratio) did not correlate with cognitive functions in the patients with liver cirrhosis. The liver disease severity had negative correlation with praxis score in previous studies, , but this is in contrast to the findings from this present study where the liver disease severity (as assessed by the Child-Pugh score) of the patients has no correlation with their score on the praxis scale. This discrepancy may be due to the small sample size of the patients in this study.
| Conclusion|| |
This study has shown that patients with liver cirrhosis without overt hepatic encephalopathy performed poorly in the domains of language, memory, attention/calculation, praxis, and total CSID score than the controls. However there was no difference in performance between the patients with liver cirrhosis and normal controls on orientation task. Also the hepatic biochemical functions and extent of liver disease severity (Child-Pugh class) did not correlate with cognitive functions of the patients with liver cirrhosis in this study.
The study is limited by a small sample size and this may be due to poor hospital attendance and late presentation with increased morbidity/mortality in the patients with liver cirrhosis in this study. Many of the patients preferred spiritual/native medicine therapy to orthodox medical therapy.
| Acknowledgments|| |
The authors are grateful to the Ibadan-Indianapolis Dementia Research Project Unit of University College Hospital, Ibadan, Nigeria for supplying the Community Screening Interview for Dementia (CSID) questionnaire that was used in this study.
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[Table 1], [Table 2], [Table 3]