Alcohol Withdrawal Is an Oxidative Stress Challenge for the Brain: Does It Pave the Way toward Severe Alcohol-Related Cognitive Impairment?

Abstract

Alcohol use is a leading cause of mortality, brain morbidity, neurological complications and minor to major neurocognitive disorders. Alcohol-related neurocognitive disorders are consecutive to the direct effect of chronic and excessive alcohol use, but not only. Indeed, patients with severe alcohol use disorders (AUD) associated with pharmacological dependence suffer from repetitive events of alcohol withdrawal (AW). If those AW are not managed by adequate medical and pharmacological treatment, they may evolve into severe AW, or be complicated by epileptic seizure or delirium tremens (DT). In addition, we suggest that AW favors the occurrence of Wernicke’s encephalopathy (WE) in patients with known or unknown thiamine depletion. We reviewed the literature on oxidative stress as a core mechanism in brain suffering linked with those conditions: AW, epileptic seizure, DT and WE. Thus, we propose perspectives to further develop research projects aiming at better identifying oxidative stress brain damage related to AW, assessing the effect of repetitive episodes of AW, and their long-term cognitive consequences. This research field should develop neuroprotective strategies during AW itself or during the periwithdrawal period. This could contribute to the prevention of severe alcohol-related brain damage and cognitive impairments.

Plasma Concentrations of Neurofilament Light Chain Protein and Brain-Derived Neurotrophic Factor as Consistent Biomarkers of Cognitive Impairment in Alcohol Use Disorder

“…Among AUD patients, there is a high prevalence of Alzheimer’s disease (recognized by tau, phosphorylated tau, and amyloid β) [ 13 ] and Wernicke–Korsakoff syndrome (associated with thiamine) [ 14 , 15 ], but in the absence of these diagnoses, cognitive dysfunction may be present [ 16 ]. The explanation of why these biomarkers are insufficient in this population could be due to the influence of additional factors in cognitive dysfunction, such as other nutritional deficiencies (i.e., low BMI, ascorbic acid deficiency, or thiamine deficiency) [ 17 , 18 ], comorbid psychiatric disorders (i.e., affective disorders) [ 19 ], as well as inflammation and oxidative stress caused by chronic alcohol intake or alcohol withdrawal episodes per se [ 20 ]. Heavy alcohol consumption throughout life triggers a proinflammatory organic state that leads to neurocognitive alterations [ 21 , 22 , 23 ].…”