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Table of Content - Volume 4 Issue 1 - October 2017
Cognitive impairment and effects of abstinence on cognition in patients with alcohol dependence syndrome
Prakash Ambekar1, Sunil Goyal2*
1Assistant Professor, Department of Psychiatry, IIMSR Medical College, Badnapur, Jalna, Maharashtra, INDIA. 2Professor, Department of Psychiatry, INHS Ashvini Hospital, Colaba, Mumbai, Maharashtra, INDIA.
Abstract Background: Alcohol dependence continues to be one of the most costly health care problems in the world. Brain damage due to alcohol intake is more common than one may think. Consequent to brain damage, cognitive impairment has been a cause of concern. In this study, the focus is to examine the cognitive and executive function in alcohol dependence syndrome patients. Ojectives of the study were to assess different domains of cognition in patients of alcohol dependence syndrome and to reassess cognitive functioning after four weeks of abstinence. Methods: A total of 50 alcohol dependent male inpatients were recruited for this study in the age range of 20 to 50 years after exclusion of other morbidities and informed consent. Baseline demographic data of cases alongwith relevant investigations were collected in first week. Alcohol use further assessed with AUDIT (Alcohol Use Disorder Identification Test). Baseline cognitive assesment using PGI Battery of Brain dysfunction (PGI-BBD) was done for the study group (Pre-treatment group) after detoxification i.e. 2 days after benzodiazepines were tapered off. While the management continued in maintainance phase, Cognitive assessment of the study group (now as post-treatment group) was repeated after one month. Results: The mean age of subjects in study was 38.40 years. The mean education of subjects was 10.30 years, the mean AUDIT score was 18.56. Different domains of cognition such as memory, intelligence and percepto-motor functioning with sub-domains of each were recorded. Study results had validated assumption that there is significant cognitive impairment among alcohol dependent cases. Dysfunction rates in all domains of memory, intelligence and perception improved post-treatment in the study group. Conclusion: The cognitive deficits may not be detected in routine clinical examinations, but with formal neuropsychological assessment using sensitive scales, the extent of impairment can be assessed both qualitatively and quantitatively. Awareness of alcohol’s effects on cognition can help health-care providers in addressing the problem and instituting appropriate treatment as well in further research on specific neuro-toxic effects of alcohol. Key Words: Alcohol dependence syndrome, Cognitive impairment, Neuro-toxic effects of alcohol.
Alcohol dependence continues to be one of the most costly health care problems in the world. Alcohol consumption is the world’s third largest risk factor for disease and disability.1 In the Indian population, increasing social acceptance and trend to follow western world are important reasons for the phenomenal increase in alcohol consumption, with the initiation age going down to 13.6 years. National Household Survey of Drug Use recorded alcohol use in the past year in only 21 percent of adult males. The prevalence of current use of alcohol ranged from a low of 7 percent in the western state of Gujarat (officially under Prohibition) to 75 percent in the North-eastern state of Arunachal Pradesh.2 Brain damage due to alcohol intake is more common than one may think. It causes white matter damage throughout brain after long term alcohol use. Acceleration of age related loss of myelin may be observed.3 Consequent to brain damage, cognitive impairment has been a cause of concern for many decades. Substance dependence has been defined as- A syndrome manifested by a behavioral pattern in which the use of a given psychoactive drug, or class of drugs, is given a much higher priority than other behaviors that once had higher value. 4 The essential feature of dependence is a cluster of cognitive, behavioral, and physiological symptoms indicating that the individual continues substance use despite significant substance-related problems.5 Before discussing the effect of alcohol on cognition, an understanding of normal cognition is required. Cognition refers to the set of interwoven processes, such as memory, language, and problem solving, that we bring to generate structures and strategies to apply to our perceptions.6 In existing literature, neuro-cognitive test measures are often grouped into a variety of domains or dimensions such as attention, memory functions, verbal skills, construction / performance skills, concept formation and reasoning.6 Among the specific functions that can be assessed are orientation, the ability to learn necessary skills, solve problems, think abstractly, reason and make judgments, the ability to retain and recall events, mathematical ability and other forms of symbol manipulation, control over primitive reactions and behaviour, language use and comprehension, attention, perception and praxis.7 The deleterious effects of alcoholism on cognitive functioning were reported in the literature as early as the 1880s. In 1881, Carl Wernicke first described an illness8, Korsakoff SS a Russian psychiatrist, described the disturbance of memory in the course of long-term alcoholism in a series of articles.9 By the 1960s, the studies by Fitzhugh and coworkers introduced the clinical neuropsychological model to the study of cognitive function in alcoholism and marked the beginning of systematic research in this area.10,11 There are fewer studies done in India for cognitive evaluation of alcohol dependent subjects. In this study, the focus is to examine the cognitive and executive function in alcohol dependent subjects and effect of abstinence from alcohol for one month. MATERIALS The study was carried out in the Department of Psychiatry, in a tertiary care center. Ethics comittee approval was taken. Study was conducted between April 2011 to May 2012. Individuals in study and comparative group were enrolled after applying inclusion and exclusion criteria and after taking informed consent. Study group: A total of 50 alcohol dependent male inpatients were recruited for this study. To avoid selection bias all successive cases admitted in the psychiatry ward, meeting inclusion and exclusion criteria were included. The subjects were all male patients in the age range of 20 years to 50 years. Inclusion Criteria
Exclusion Criteria
Tools
PGI Battery of Brain dysfunction (PGI-BBD): The PGI-BBD was developed by Dr Dwaraka Prasad and Dr Santosh K Verma of Post Graduate Institute of Medical Education and Research, Chandigarh in 1990. This is a comprehensive battery and consists of tests to measure both verbal and performance quotient, memory and visuo-special ability. PGI-BBD is taken as a measure of cognitive functioning because it is standerdised on Indian population.It is battery of five tests It consists of following tests
For each test rating, Dysfunctional rating is graded into three categories i.e. 0, 2 and 3, raw score was changed to converted score, which in turn converted to dysfunctional, in the grade of increasing severity of impairment. Zero dysfunctional rating indicates no impairment, one indicates mild impairment and three indicates significant impairment on a given domain. METHODS Enrollment of cases and controls was done after applying inclusion and exclusion criteria. HAM-D and HAM-A scale was given to rule out depressive and anxiety disorders respectively. Informed consent was taken from subjects. Baseline demographic data of cases alongwith relevant investigations mentioned in proforma were entered in semi-structured proforma in first week of admission. Alcohol use further assessed with AUDIT (Alcohol Use Disorder Identification Test). Baseline cognitive assesment using PGI-BBD was done for study group (Pre-treatment group) after detoxification ie 2 days after benzodiazepines were tapered off. Patients were managed with enforced abstinence, vitamin supplements, alcohol psycho education, individual and group psychotherapy and relapse prevention counseling. Suitable anti-craving agent was added in fourth week of treatment. Cognitive assessment of study group (post-treatment group) was repeated after one month of initial assessment. Ethics committee approval was taken for this study. The data was analysed using Statistical Package for Social Sciences (SPSS) version 20. To check for normality, the Shapiro-Wilk test was applied. Pre-treatment and post-treatment group was compared with the help of Wilcoxon Signed Ranks Test. Correlation of age of onset of alcohol use, years of alcohol consumption and AUDIT scores with different domains of cognition is done using Spearman’s rank correlation coefficient. P-values less than 0.05 were taken as significant.
RESULTS The present study was carried out amongst 50 male participants. The mean age of subjects in study was 38.40 years.
Table 1: Mean scores of alcohol related variables in the study group (n=50)
It was seen from Table 1 that mean age of onset 23.90 years of age (Range- 15-38 years). Within the group the years of consumption of alcohol ranged from 3 to 29 years with mean duration being 14.48 years..The mean AUDIT score was 18.56 with range 14 to 27. Of the total alcohol dependent patients, 74% (n=37) were tobacco consumers or smokers and mean duration of tobacco consumption was 10.96 years. Table 2: PGI-Memory Scale Dysfunctional Scores
As seen from Table 2 that dysfunction rating on PGI-MS revealed that 22 (44%) pre-treatment group patients had dysfunctional remote memory as compared to 21 (42%) in post-treatment. Recent memory dysfunction was 21 (42%) and 14 (28%) in pre-treatment, post-treatment groups respectively. Mental balance dysfunction was 33(66%) and 33 (66%) in pre-treatment and post-treatment respectively. Attention and concentration dysfunction was 24 (48%) and 7 (14%) in pre-treatment and post-treatment respectively. Delayed recall dysfunction was 37 (74%) and 24 (48%) in pre-treatment and post-treatment respectively. Immediate recall dysfunction was 27 (54%) and 20 (40%) pre-treatment and post-treatment respectively. Dysfunction for retention of similar pairs was 23 (46%) and 12 (24%) in pre-treatment and post-treatment respectively. Dysfunction for retention of dissimilar pairs was 46 (92%) and 36 (72%) in pre-treatment and post-treatment respectively. Visual retention dysfunction was 45 (90%) and 31 (62%) pre-treatment and post-treatment respectively. Visual recognition dysfunction was 30(60%) and 21 (42%) in pre-treatment and post-treatment respectively. Table 3: Comparison of memory of pre-treatment group and post-treatment group after one month of abstinence
As seen in the Table 3 that no significant difference was found in the mean scores of remote memory of patients after admission as compared to that after one month of abstinence (p=0.157). The mean scores of recent memory in pre-treatment condition is lesser than that of post treatment condition and this difference was found to be statistically significant (p = 0.020). This shows that there has been an improvement in the cognitive condition in the study group post treatment. Significant difference was found in other domains of cognitions also which indicates that there has been an improvement in patients after treatment (p<0.001).
Table 4: Dysfunctional rating of performance quotient
As Table 4 shows that dysfunctional ratings for performance quotient (PQ) and there in was impairment of 40 (80%), 18 (36%) and 12 (24%) in pre-treatment and post-treatment respectively. Further PQ evaluation revealed that mean scores of 69.54 and 82.82. There was significant improvement between pre-treatment and post-treatment group (p<0.001).
Table 5: Comparison performance quotient of pre-treatment group and post-treatment group after one month of abstinence
Note: P/K –Ratio of test quotient of pass along test and Kohs Block design test. Table 5 shows, statistically significant difference in mean scores of performance quotient of pre-treatment group and post-treatment group (p<0.001). This implies significant improvement in performance quotient after one month of abstinence and treatment.
Table 6: Dysfunctional rating of Verbal Adult Intelligence Scale in subjects
As Table 6 shows, testing for Verbal quotient revealed that 28 (56%) and 20 (40%) dysfunction Pre-treatment and post-treatment respectively in Information quotient. Digit span dysfunction observed to be 8 (16%) and 7 (14%) Arithmetic dysfunction observed to be 5 (10%) and 4 (8%) the respective groups. Dysfunction in comprehension quotient was observed to be 24 (48%) and 15 (30%) in the pre-treatment and post-treatment group respectively. Table 7: Comparison of Verbal Quotient of pretreatment group and post-treatment group after one month of abstinence
Table 7 shows that there was significant difference in mean scores of pre-treatment and post-treatment group (p<0.05). This shows significant improvement in verbal quotient of study group after treatment and a month of abstinence.
Table 8: Dysfunctional rating of Perceptomotor functioning:
Table 8 shows the prevalence of perceptomotor impairment is more in pre-treatment group as compared to post-treatment group. Table 9: Comparison of percepto-motor task after admission and after one month of abstinence
Table 9 shows, statistically significant difference in mean scores of Nahor Benson test in pre-treatment group and post-treatment group (p<0.001). This implies significant improvement in percepto-motor task after treatment and abstinence for one month. Table 10: Comparison of percepto-motor task of pre-treatment group and post-treatment group after one month of abstinence
Table 10 shows, statistically significant difference in mean scores of BVMGT in pre-treatment group and post-treatment group (p<0.001). This implies significant improvement in percepto-motor task after treatment and abstinence for one month. Dysfunction on Nahor Benson testing was observed to be 19 (38%) and 10 (20%) in pre-treatment and post-treatment respectively. Nahor-Benson testing on pre-treatment and post-treatment group had shown mean error scores of 2.16 and 1.54 and statistically significant post-treatment improvement. Dysfunction on Bender Visual – Motor Gestalt testing observed to be 33 (66%) in 13 (26%) in pre-treatment and post-treatment respectively. Bender Visual – Motor Gestalt on pre-treatment and post-treatment group had shown mean raw scores of 5.30 and 3.60 and statistically significant post-treatment improvement. Table 11: Correlation of years of drinking with various cognitive domain of study group on admission (n=50)
Note-Figures in the table reflects Spearman’s rank correlation coefficient * Indicates correlation is significant at p<0.05, **Indicates correlation is significant at p<0.01 As Table 11 shows, increase in years of consuming alcohol of study group is associated with more cognitive impairment in all domains (p<0.05) except with visual retention and recognition. AUDIT scores shows negative correlation with remote memory, mental balance, attention and concentration, delayed recall, retention of similar and dissimilar pairs and comprehension. There is no significant correlation found between age of onset of alcohol use and cognitive impairment except on Nahor Benson test (p=0.007).
DISCUSSION The mean age of subjects in study was 38.40 years. The mean education of subjects in two groups was 10.30 years. PGI-BBD scoring system is also standardized and adjusted for age and education. Hence the factor of age and education affecting cognitive functioning is eliminated. Memory: In the present study, there was lesser prevalence of impairment in various domains of memory on PGI- Memory Scale in the post-treatment group than the pre-treatment group. This suggests that the impairment in memory is reversible in some of the patients after treatment and abstinence for one month. When pre-treatment group is compared to post-treatment group after one month of abstinence, there is significant improvement in recent memory, mental balance, attention and concentration, immediate recall (sentences), delayed recall (words), retention for similar and dissimilar pairs, visual retention and visual recognition. The improvement observed in remote memory in post-treatment group was not significant. Our results are in concordance with few previous studies 16,17, 18, 19, 20, 21, 22,, 23 Intelligence: Performance quotient: Present study shows that dysfunctional rating of Revised Bhatia’s short Battery of Performance tests of Intelligence in study group. There is significant improvement in performance quotient of the study group after one month of abstinence. This suggests that the impairment in performance quotient improves in the patients after treatment and abstinence for one month. On evaluation of Performance Quotient (PQ), there was significant improvement in post-treatment group in comparison to pre-treatment group (p<0.001). Verbal quotient: Our study that there was lesser prevalence of impairment in domains of verbal intelligence on dysfunctional rating of Verbal Adult Intelligence Scale in post-treatment group than pre-treatment group. This suggests that the impairment in Verbal Quotient is reversible in some of the patients after treatment and abstinence for one month. On analysis of sub-domains of Verbal Quotient (VQ) on Verbal Adult Intelligence scale, there is significant improvement in information, digit span, arithmetic and comprehension quotients in post-treatment group. These results are in concordance with study Bhat et al.24 The result of more improvement in verbal quotient as compared to performance quotient is also reported in previous studies. These studies observe impairments in fluid-intelligence skills of visuo-spatial processing and problem solving ie performance quotient persist during the intermediate-term abstinence period in most recovering alcoholic dependent patients, as evidenced by lower Performance IQ subtest scores relative to Verbal IQ subtest scores.25.26 Perceptomotor Functioning: Present study revealed that there was lesser prevalence of impairment in percepto-motor functioning on Nahor Benson test as well as Bender Gestault test in post-treatment group than pre-treatment group. This suggests that the impairment in percepto-motor functioning may be reversible in the patients after treatment and abstinence for one month. Tables 10 and 11 show on evaluation of percepto-motor functioning, there is significant improvement in post-treatment groups. This is in concordance with study done by Bhat et al.24 and few other studies 27,28 Correlation of cognitive impairment: The correlation of cognitive impairment of pre-treatment group with age of onset of alcohol use, years of alcohol consumption and AUDIT scores. There is no significant correlation found between age of onset of alcohol use and cognitive impairment. Increase in years of consuming alcohol of study group is associated with more cognitive impairment in all domains (p<0.05) except with visual retention and recognition. AUDIT scores shows negative correlation with remote memory, mental balance, attention and concentration, delayed recall, retention of similar and dissimilar pairs and comprehension. Alcohol use over a period of time causes brain damage. It causes widening of sulci and ventricular enlargement 29,30,31,32. Widened sulci have been found consistently in patients of all ages with chronic alcoholism. This widening is particularly apparent in the frontal and the fronto-parieto-temporal areas.31Also, alcoholism can interfere with memory, emotion, and other functions associated with damage to limbic system and diencephalic structures. This can also cause diffuse cortical damage affecting the functioning of both brain hemispheres (e.g., abstracting and problem-solving abilities, poor attention, disinhibition, and perseverative responding). Impairment in performance and verbal quotient may be attributed to cerebral atrophy.33 As several studies of alcoholism have reported significant correlations between intellectual impairment and cerebral atrophy.34,35,36 Nutritional deficiencies and alcohol withdrawal seizures which are commonly present in alcohol dependent patients may be contributing factor for cognitive impairment.37 Improvement in various domains of cognition suggests reversibility of brain damage with abstinence of one month and treatment. It has been found that cerebral atrophy reverses over time as abstinence continues, with more complete recovery of cortical volume in younger than in older alcoholics.21,38 Another explanation for improvement in cognitive functioning is the ability of the brain to compensate for a decline in function. One could implicate that plasticity, i.e. the ability of the brain to modify its organization and ultimately its function, may be one of the possibilities to account for improvement in cognitive functioning that is seen. Several factors are known to affect this plasticity and some of the known ones are experience, gonadal hormones, anti-inflammatory agents, growth factors, dietary factors, genetic factors, stress and brain injury.39 Study done by Bhat et al 24 shows significant difference in almost all domains of cognition was in contrast to this study showing significant difference in only some of the domains. This discordance in above results may be due to high baseline mean scores of participants in the study group of above subscales as compared to those of the study done by Bhat et al.24 Previous studies have shown that longer period of abstinence is needed so as to assess the recovery of cognitive functioning in alcohol dependent patients after abstinence.40,41,42 This study had also shown positive correlation between years of alcohol consumption and various domains of cognitive functioning. This indicates cumulative deleterious effect of alcohol on brain. However, there are inconsistent results of correlation between AUDIT scores and various cognitive domains of study group. This may be attributed to denial and minimisation defense mechanisms, which are commonly seen in alcohol dependent patients.
LIMITATIONS Practice effect can be a confounding factor in analysis and may have some role in improvement of scale scores in the study group, post-treatment. In this study, only male patients were studied so we can’t generalise these findings to females. Study group was re-evaluated after one month but as discussed above some studies mention further improvement in cognitive domains as period of abstinence increases. So the period of one month of abstinence from alcohol is inadequate for assessment of complete improvement of cognitive functioning.
CONCLUSION Study had validated assumption that there is significant cognitive impairment among alcohol dependent cases. These deficits may not be detected in routine clinical examinations, but with formal neuropsychological assessment using sensitive scales, the extent of impairment can be assessed both qualitatively and quantitatively. Dysfunction rates in all domains of memory, intelligence and perception improved post-treatment in the study group. Post-treatment, the study group had significant improvement in recent memory, mental balance, attention and concentration, immediate and delayed recall, retention of similar and dissimilar pairs, visual retention and recognition, verbal and performance quotient and percepto-motor functioning. Increase in years of consuming alcohol of study group is associated with more cognitive impairment in memory, intelligence and percepto-motor ability. Awareness of alcohol’s effects on cognition can help health-care providers in addressing the problem and instituting appropriate treatment. This study is among the rare Indian studies to assess cognitive function in alcohol dependent patients. Since it is an interventional study, it analyses effects of one month of abstinence after month and treatment. It not just establishes the presence of these residual cognitive differences in alcohol dependent patients but also correlates them with various variables.
REFERENCES
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