Effect of alcohol-dependence on cognitive performance in middle-aged men: Preliminary results

INTRODUCTION

Alcoholism is associated with brain damage and poor cognitive functioning.^[1] The alcohol-related neuropathology and cognitive impairment for different etiological factors, such as alcohol, thiamine levels, and age vulnerability show inconsistent evidence.^[1-3] This variation is due to methodological limitations^[4] in terms of study design, that is, population selection, age criteria, and a variety of neuropsychological tests measured. Few studies have also shown the effects of alcohol consumption on poor cognitive performance, particularly executive functions,^[5-11] episodic and working memory.^[10] In the present scenario, all clinicians use subjective analysis to assess the cognitive status of alcohol-dependent patients. Further, the assessment of how rapidly cognition is progressing has important clinical implications. For this, a biological marker for rapid cognitive decline would be of importance because at-risk patients can be targeted early for non-pharmacological, medical, and psychosocial interventions to slow deterioration. Thiamine, also known as Vitamin B1, exerts neuroprotective^[6,9,12] effects by maintaining blood–brain barrier integrity and is particularly, studied as a biological marker for cognitive decline.^[13] To date, no published literature is available to show the association between thiamine blood levels and cognition in alcohol-dependent patients among the Indian middle-aged population. With this background, the present study was designed with the primary objective of evaluating the effect of alcohol dependence on neurocognitive functions using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and cognitive biomarkerthiamine (Vitamin B1) levels among Indian middle-aged (36–55 years)^[4] men with alcohol dependence compared to non-alcohol dependent subjects. The secondary objective was to assess the correlation between the effect of alcohol dependence (alcohol use disorder identification test [AUDIT] scores) on the MoCA scores, MMSE scores, and serum thiamine levels and also provide a scientific association between the serum thiamine levels and MoCA scores.

MATERIALS AND METHODS

The present study was a cross-sectional pilot study with a comparison group including 82 right-handed, middle-aged (36–55 years) men with and without alcohol dependence (n = 41 each), carried out at a tertiary care hospital (All India Institute of Medical Sciences [AIIMS], Bathinda) in Western Punjab. This study was conducted by the Helsinki Declaration and was approved by the Institutional Ethics Committee (IEC) (Ref. No.: IEC/AIIMS/BTI/085; dated 17/03/2021). All participants provided written informed consent. The study was registered at the Clinical Trial Registry India (CTRI), CTRI/2021/12/039034. The study was conducted from September to November 2021 (the 2 months of the study period for the undergraduate Indian Council of Medical Research, New Delhi-STS-project 2020) in the Department of Psychiatry in association with the Department of Physiology and the Department of Biochemistry at AIIMS, Bathinda. The sample size for the study was calculated using n-master 2.0^[14] software assuming the prevalence^[15] of cognitive decline between 30% to 80% and 95% confidence interval with an absolute precision of 10% which came out to be 41 for each group.

Alcohol-dependent (Group A) participants were recruited on the basis of dependency on alcohol assessed by the International Classification of Disease Tenth Edition (ICD-10) criteria for diagnosis of alcohol dependence along with AUDIT.^[16] These patients came under F10 (alcohol withdrawal) according to ICD-10 criteria. The inclusion criteria include those participants who were willing to participate in the study program after the detoxification phase of 7–10 days was over. The average years of alcohol consumption were found to be 11.36 ± 6.85 (mean ± standard deviation) years. The exclusion criteria include patients with serious medical conditions, seriously sick, non-ambulatory, non-cooperative patients, with significant liver disease (cirrhosis of the liver), history of drug dependence other than nicotine or caffeine, clinical evidence of Wernicke–Korsakoff syndrome (WKS), a significant history of head trauma or brain surgery, organic brain syndrome, psychotic disorder, major depressive disorder, and bipolar disorder. Only clinical history was utilised to exclude other major psychiatric disorders.

An age-matched comparison group, Group B, that is, non-alcohol-dependent subjects was recruited from among the caregivers of patients attending the psychiatry outpatient department. The non-alcohol dependence was analysed on the basis of AUDIT scores. The subjects in the control group were non-alcohol dependent and few were social drinkers who were considered in Zone 1 based on the AUDIT scores according to the World Health Organisation (WHO) criteria.^[9,17,18] Exclusion criteria include those subjects having any serious medical problem or psychiatric illness on anamnestic recall, taking alcohol within 24 h of cognitive function assessment, a significant history of head trauma or brain surgery, history of drug dependence other than nicotine or caffeine. The aim of including the age-matched non-alcohol-dependent group was only to compare the natural variation in cognitive functions with the alcohol-dependent group.

We recorded sociodemographic data including age, height (stadiometer, Holtain Ltd., UK) body weight (digital weighing balance, Seca, Germany), body mass index (BMI), education level (<12 years, equal to 12 years and higher than 12 years)^[19] and family history of alcohol/drug use disorders through a family tree.

RESULTS

The present study included a total of 82 male participants with (n = 41) alcohol-dependent patients (age 41.72 ± 8.79 years) and (n = 41) non-alcohol-dependent subjects (age 43.34 ± 9.53 years) after meeting the inclusion and exclusion criteria [Table 1]. The alcohol-dependent patients had an average of 11.36 ± 6.85 years of alcohol consumption. No statistically significant differences were observed between alcohol-dependent and non-alcohol-dependent participants for age, education, BMI, systolic blood pressure, and diastolic blood pressure [Table 1].

Table 1: Demographic data and clinical parameters for study participants.

Neurocognitive assessments

For neurocognitive functions, both MMSE (26.46 ± 2.08; 29.09 ± 1.23; P = 0.001) and MoCA scores (23.14 ± 2.70; 28.18 ± 1.64; P = 0.008), respectively, were found to be significantly less for the alcohol- dependent patients when compared with the non-alcohol-dependent group. Further, the serum Vitamin B1 (thiamine) levels were found to be significantly (P = 0.021) low for alcohol-dependent patients (1509.43 ± 898.63 pmol/L) versus non-alcohol-dependent subjects (1862.81 ± 741.30 pmol/L) [Table 1].

Correlations between the different neurocognitive tests

Further, the correlations between the different neurocognitive tests, that is, MoCA scores, MMSE scores, and Vitamin B1 (thiamine) levels with AUDIT scores were evaluated using the Pearson correlation coefficient. The MoCA scores (r = −0.323; P = 0.039) and Vitamin B1 levels (r = −0.460; P = 0.002) had a significant negative correlation with AUDIT scores in middle-aged men with alcohol dependence [Figures 1a and b]. However, the MMSE scores were negatively correlated with AUDIT scores but no statistical significance (r = −0.215; P = 0.176) was observed between them. Importantly, the present study observed a significant (r = 0.550; P = 0.01) positive correlation between serum thiamine levels with MoCA scores [Figure 2].

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Figure 1:

(a) Correlation of alcohol dependence identification test (AUDIT) scores on thiamine (Vitamin B1) levels in alcohol-dependent patients, (b) correlation of alcohol use disorder identification test (AUDIT) scores on Montreal Cognitive Assessment (MoCA) scores.

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Figure 2:

Correlation of Vitamin B1 levels with Montreal Cognitive Assessment (MoCA) scores in alcohol-dependent patients.

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Sub-scores of cognitive domains assessed by MMSE and MoCA

Based on the distribution of each cognitive domain sub-score in total samples assessed by different items of MMSE and MoCA [Table 2]. The performance of orientation, execution, naming, registration, visuoconstructional skills, writing, and repetition was found to be significantly (P < 0.05) decreased in alcohol-dependent patients versus non-alcohol-dependent group using MMSE maximum scores; whereas orientation, execution, calculation, visuoconstructional skills and recall functions were found to be significantly (P < 0.05) decreased in alcohol-dependent patients versus non-alcohol-dependent group using MoCA test. Importantly, calculation, recall, visuoconstructional skills, and writing are affected in alcohol-dependent patients more significantly (P < 0.05) than non-alcoholic-dependent subjects.

Table 2: Cognitive sub-domain analysis of MMSE and MoCA scores for Groups A and B participants.

DISCUSSION

To the best of our knowledge, this is the first report from the Indian population providing psycho-biochemical evidence that cognitive functions deteriorate in middle-aged men with alcohol dependence. Further, the present study also focussed on the sub-analysis of the cognitive domains of MMSE and MoCA. It has been observed that calculation, recall, visuoconstructional skills, and writing are significantly affected more in our study population when compared with other study research findings.^[10,23,24] This impairment in cognitive performance of sub-domains may be due to the alcohol addiction process that affects the thiamine metabolism^[6,9,12] and leads to neurotoxicity which further affects the brain areas, especially shrinkage of the hippocampal region.^[25]

The previous research findings observed the uncertainty in the association between alcohol drinking and cognitive dysfunctions. Some studies have found no association between alcohol drinking and cognitive impairment^[26,27] or Alzheimer’s disease,^[28] whereas others have found an association between heavy drinking and increased risk of dementia.^[26,27,29] Some have claimed there is a J or U-shaped relation between alcohol drinking and cognitive impairment^[2,4,10,13] or dementia^[7,8,13] Importantly, these studies showed inconsistency in their findings due to the methodological limitations in terms of study design about population selection, age criteria and a variety of neuropsychological tests used and did not validate it by any clinical or diagnostic criteria for defining the mild cognitive impairment.^[4] For this, the present study has also provided the associations between alcohol dependency with different neuropsychological tests. We observed a non-linear relationship between alcohol dependency (AUDIT scores) with cognitive tests, that is, MoCA scores. Importantly, serum thiamine levels showed a linear relationship with MoCA cognitive scores. This linear relationship provides the scientific affirmation that cognitive domains are affected due to a decrease in serum thiamine levels. Reduced cellular thiamine concentrations, combined with the toxic effects of ethanol and acetaldehyde, are considered crucial factors contributing to cognitive impairment among individuals with alcohol dependence and also heighten the risk of developing WKS. This finding provides the scientific platform for the need for early detection of cognitive decline.

CONCLUSION

Based on the significant positive association between serum thiamine levels with MoCA scores, both may be used as a screening tool for the early detection of cognitive impairment in patients with alcohol dependence.