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

Abstract

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.

Cerebrospinal Fluid Monocyte Chemoattractant Protein‐1 in Alcoholics: Support for a Neuroinflammatory Model of Chronic Alcoholism

“…Previously, we found that magnetic resonance imaging measures of brain shrinkage in alcoholism were correlated with liver inflammation as quantified by serum GGT (Chen et al, 2012). The present study expands on this finding by demonstrating that the severity of liver inflammation is correlated with neuroinflammation as indexed by the concentration of MCP-1 in CSF.…”

Profiles of impaired, spared, and recovered neuropsychologic processes in alcoholism

“…Smaller white matter volumes likewise have been reported (Harper et al, 1990; Pfefferbaum et al, 1995; Pfefferbaum et al, 2001b; Chen et al, 2012), including the corpus callosum (see Figure 1) (Pfefferbaum et al, 1996; Agartz et al, 1999; Ruiz et al, 2013). Smaller brain volume is accompanied by larger CSF volume (Pfefferbaum et al, 1992; Pfefferbaum et al, 1998; Agartz et al, 1999; Bendszus et al, 2001; Pfefferbaum et al, 2001b; Chen et al, 2012), and researchers have reported larger volumes of the lateral ventricles (Zipursky et al, 1989; Pfefferbaum et al, 1998; Pfefferbaum et al, 2001b; Ruiz et al, 2013) and the third ventricle (Pfefferbaum et al, 2001b). …”

“…Relatively smaller volumes have been noted not only in total brain size (Pfefferbaum et al, 1992; Mann et al, 2005; Chen et al, 2012) including the cerebellum (Chanraud et al, 2007), but also in cerebral subdivisions and regional areas (Pfefferbaum et al, 1992; Pfefferbaum et al, 2001b; Makris et al, 2008; Fein et al, 2009; Chen et al, 2012) and numerous subcortical structures (Chanraud et al, 2007; Makris et al, 2008). Smaller white matter volumes likewise have been reported (Harper et al, 1990; Pfefferbaum et al, 1995; Pfefferbaum et al, 2001b; Chen et al, 2012), including the corpus callosum (see Figure 1) (Pfefferbaum et al, 1996; Agartz et al, 1999; Ruiz et al, 2013).…”

“…Relatively smaller volumes have been noted not only in total brain size (Pfefferbaum et al, 1992; Mann et al, 2005; Chen et al, 2012) including the cerebellum (Chanraud et al, 2007), but also in cerebral subdivisions and regional areas (Pfefferbaum et al, 1992; Pfefferbaum et al, 2001b; Makris et al, 2008; Fein et al, 2009; Chen et al, 2012) and numerous subcortical structures (Chanraud et al, 2007; Makris et al, 2008). Smaller white matter volumes likewise have been reported (Harper et al, 1990; Pfefferbaum et al, 1995; Pfefferbaum et al, 2001b; Chen et al, 2012), including the corpus callosum (see Figure 1) (Pfefferbaum et al, 1996; Agartz et al, 1999; Ruiz et al, 2013). Smaller brain volume is accompanied by larger CSF volume (Pfefferbaum et al, 1992; Pfefferbaum et al, 1998; Agartz et al, 1999; Bendszus et al, 2001; Pfefferbaum et al, 2001b; Chen et al, 2012), and researchers have reported larger volumes of the lateral ventricles (Zipursky et al, 1989; Pfefferbaum et al, 1998; Pfefferbaum et al, 2001b; Ruiz et al, 2013) and the third ventricle (Pfefferbaum et al, 2001b).…”

“…Significant volume reductions have been reported in the frontal lobes (Pfefferbaum et al, 1992; Agartz et al, 1999; Kubota et al, 2001; Chanraud et al, 2007; Chen et al, 2012) including reduced gray matter in dorsolateral prefrontal cortex (Chanraud et al, 2007; Makris et al, 2008) and anterior cingulate cortex (Chanraud et al, 2007). Analyses of cortical thickness in alcoholics have demonstrated that the frontal lobes are particularly vulnerable to thinning (Fortier et al, 2011).…”