Mildly Disturbed Hepatic and Pancreatic Function During Early Abstention From Alcohol Is Associated With Brain Atrophy and With Disturbed Psychometric Performance

Junghanns, Klaus; Backhaus, Jutta; Dageförde, J.; Brückmann, H.; Wetterling, Tilman

doi:10.1093/alcalc/agh028

Cited by 9 publications

(5 citation statements)

References 28 publications

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“…Our data suggest that these pathophysiological mechanisms may also explain, at least partially, executive dysfunction in AL without severe hepatic encephalopathy. Our findings, in agreement with previous studies showing a relationship between mental flexibility and liver function (assessed by GGT level [ 24 ]), reinforce thus that alcohol-related liver disease has deleterious effects on executive functions. However, in the present study, neither GGT level nor SGOT/SGPT ratio was related to patients’ executive results [ 25 ].…”

Section: Discussionsupporting

confidence: 93%

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Clinical and Biological Risk Factors for Neuropsychological Impairment in Alcohol Use Disorder

et al. 2016

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The effects of alcoholism on cognitive and motor functioning are heterogeneous. While the role of some factors (patterns of alcohol consumption, eating habits or associated liver disease) has been hypothesized, the origins of this heterogeneity remain difficult to establish. The goals of the present study were thus to identify the clinical and biological risk factors for alcohol-related neuropsychological impairments and to determine the threshold beyond which these risk factors can be considered significant. Thirty alcoholic patients and 15 healthy controls had a blood test and underwent a neuropsychological examination. Alcohol severity measures, and liver, thiamine and malnutrition variables, were included in logistic regression models to determine the risk factors for cognitive and motor impairments (executive functions, visuospatial abilities, verbal episodic memory, ataxia), as well as those related to the severity of patients’ overall neuropsychological profile (moderate or severe impairments). Liver fibrosis was found to be a risk factor for executive impairments and also for ataxia, when it was associated with long-term alcohol misuse and symptoms of withdrawal. Altered thiamine metabolism was solely predictive of verbal episodic memory impairments. This combination of biological abnormalities was associated with a profile of moderate neuropsychological impairments. Malnutrition was associated with a profile of more severe impairments. Malnutrition, altered liver function and thiamine metabolism explain, at least partially, the heterogeneity of alcohol-related neuropsychological impairments. Our findings could allow clinicians to identify patients at particular risk of severe neuropsychological impairments before the onset of irreversible and debilitating neurological complications.

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Section: Discussionsupporting

confidence: 93%

“…Liver dysfunction is known to be responsible for neuropsychological impairments in patients with cirrhosis [ 23 ]. In AL without cirrhosis, correlations have been found between the level of GGT and mental flexibility [ 24 ], although a more recent study failed to replicate this finding [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical and Biological Risk Factors for Neuropsychological Impairment in Alcohol Use Disorder

et al. 2016

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“…Junghanns and co-workers [54] found mildly disturbed liver and pancreatic parameters (alpha amylase (AA) and gamma glutamyl transpeptidase (GGT)) but not fatty liver itself to be associated with brain atrophy and decreased cognitive performance. However, most recently, O'Mahony could not find any association between liver function and cognitive performance in recently abstinent alcohol-dependent patients [55].…”

Section: Studies That Aimed At Factors Causing or Influencing The Cogmentioning

confidence: 99%

Neuropsychological functioning and alcohol dependence

Scheurich

2005

Current Opinion in Psychiatry

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Recent studies found widespread compromised fronto-cortico-cerebellar circuits to underlie cognitive deficits. The inclusion of cerebellar structures to support functions traditionally associated with cortical and even prefrontal structures is important. However, most importantly, alcohol-dependent patients use additional and generally higher-order executive functions to compensate for deficient task performance. The compensatory mechanisms might help to explain close to normal functioning in basic cognitive domains enabled by support of executive components. But deficits in executive functions themselves might emerge more directly. New approaches concerning executive functioning, analyzing functional components of executive tasks, found response inhibition and decision-making to be impaired but normal performance in simple working memory tasks. Multiple withdrawals have been shown to lead to a higher degree of executive deficit. The causing mechanism underlying the attentional bias induced by alcohol-related words (stroop effect) is still under debate. Correlation of cognitive deficits with therapy outcome turned out to be weak. However, important interactions of cognitive deficits with personality, therapy-setting and successful coping, together with the finding that cognitive performance of alcohol-dependent patients could be enhanced by motivating instructions, might open new strategies in treatment planning and cognitive rehabilitation.

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“…In addition, GGT has also been shown to be associated with lipid peroxidation in hepatocytes (Paolicchi et al., 1997). Although liver function indices have been shown to be associated with brain shrinkage as measured by computed tomography (Junghanns et al., 2004; Mutzell, 1992) in patients with alcohol dependence, using categorical grouping in Mutzell’s study and not controlling age and drinking characteristics in Junghanns’s study might limit the interpretation of these results. Pfefferbaum and colleagues (2004) have found high, but not significant, correlations between serum GGT level and cortical white matter ( r = −0.48) and third ventricle size ( r = 0.42) in patients with alcohol dependence.…”

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confidence: 98%

Relationship Between Liver Function and Brain Shrinkage in Patients with Alcohol Dependence

Chen

Walker

Momenan

et al. 2011

Alcoholism Clin & Exp Res

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Background Oxidative stress has been proposed as one of the mechanisms of alcohol-induced brain shrinkage and alcohol-induced hepatotoxicity. The study aim was to assess the correlations between liver function and brain volume measurements in patients with alcohol dependence. Methods We recruited 124 patients with alcohol dependence and 111 healthy control subjects from National Institute of Health, National Institute on Alcohol Abuse and Alcoholism inpatient alcohol treatment program. Gamma glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT) as well as hematocrit (Hct) and albumin were assayed shortly after admission. MRI examination was conducted in both groups (after 3-week abstinence in the patient group). We used stepwise linear regression analyses to determine the variables most strongly correlated with brain shrinkage. Results Patients with alcohol dependence had lower brain volume (BV), and greater brain shrinkage as measured by gray matter ratio (GMR), white matter ratio (WMR), and brain ratio (BR) and higher CSF ratio (CSFR) compared to their healthy counterparts. Age and sex were significantly correlated with some brain volume measurements in both patient and control groups. Body mass index (BMI) was significantly correlated with CSFR, BR, GMR, and WMR; Hct with CSFR and BR; serum GGT level with BV, CSFR, BR, GMR, and WMF in the patient group. No biological variables were correlated with brain volume indices in the control group. In gender-stratified analysis, age was significantly correlated with brain shrinkage in male patients, but not in female patients. Serum GGT level in male and female patients, Hct in male patients, and AST levels in female patients were significantly correlated with brain shrinkage. Conclusions Our results showed that the higher levels of liver function indices, especially GGT, correlated with brain volume shrinkage as measured using CSFR, BR, GMR, and WMR in patients with alcohol dependence, but not in controls. Serum GGT level outweighed aging effect on brain shrinkage in female patients.

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Mildly Disturbed Hepatic and Pancreatic Function During Early Abstention From Alcohol Is Associated With Brain Atrophy and With Disturbed Psychometric Performance

Abstract: After detoxification from alcohol even mildly disturbed liver and pancreatic parameters, but not fatty liver itself, are associated with signs of brain atrophy and impaired psychometric performance. Age may be a confounding or contributing factor.

Cited by 9 publications

References 28 publications

Clinical and Biological Risk Factors for Neuropsychological Impairment in Alcohol Use Disorder

Clinical and Biological Risk Factors for Neuropsychological Impairment in Alcohol Use Disorder

Neuropsychological functioning and alcohol dependence

Relationship Between Liver Function and Brain Shrinkage in Patients with Alcohol Dependence

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