Long-term impact of alcohol on the brain Wikipedia

February 19, 2021

One study found no difference in the number of neocortical neurons between the brains of people who misuse alcohol and those who do not. Continuing to drink despite clear signs of significant impairments can result in an alcohol overdose. An alcohol overdose occurs when there is so much alcohol in the bloodstream that areas of the brain controlling basic life-support functions—such as breathing, heart rate, and temperature control—begin to shut down. Symptoms of alcohol overdose include mental confusion, difficulty remaining conscious, vomiting, seizure, trouble breathing, slow heart rate, clammy skin, dulled responses (such as no gag reflex, which prevents choking), and extremely low body temperature. Misuse of alcohol during adolescence can alter brain development, potentially resulting in long-lasting changes in brain structure and function.

The impact of alcohol can be observed early on, moderate to heavy drinking during adolescence leads to observable differences to non-drinkers, but this is further confounded by risk factors to unhealthy drinking patterns and alcohol dependence. However, though MRI research will be important in advancing our understanding of the impact of alcohol on the brain we cannot infer harm solely from alterations to brain structure. Early case studies highlighted striking morphological anomalies, most notably thinning of the corpus callosum and enlargement of ventricles, but subsequent radiological investigations have highlighted there is considerable variability in the impact of FASD on brain development 58. Quantitative analyses of brain macrostructure in FASD have repeatedly found lower grey and white matter volume along with increased thickness and density of cortical grey matter 59. Crucially, findings have found no morphological differences in the occipital lobe, suggesting that not all brain structures are affected equally. Brain phenotypes of FASD have consistently been recapitulated in animal models and highlight the modulating role of timing and alcohol exposure 60.

Roles

Understanding these specific vulnerabilities highlights the importance of responsible drinking to mitigate the long-term neurological consequences of alcohol consumption. Alcohol metabolism generates reactive oxygen species (ROS) that overwhelm the brain’s antioxidant defenses. The brain’s vulnerability to oxidative stress is particularly pronounced in regions with high metabolic activity, such as the cerebral cortex and cerebellum, where long-term alcohol use can lead to noticeable atrophy and functional decline. The cognitive decline that is frequently observed in heavy alcohol drinkers could be attributed to increased neuronal cell death and reduced functionality of surviving cells due to oxidative stress.

Alcohol Overdose

Drugs of abuse, including alcohol, interact with and influence this system and several fMRI paradigms have been developed to probe such effects. One of the most commonly used to probe non-drug related reward sensitivity is the monetary incentive delay (MID) task 98, whereas to measure drug-related reward, cue-reactivity tasks are usually employed 99. Most commonly these tasks consist of presenting the individual with static or video imagery of a ‘cue’, typically drug or related paraphernalia, however, smell and taste can also be used.

Structural and Volumetric Changes

While this does not equate to brain cell death, it demonstrates how alcohol can acutely impair cognitive function by interfering with essential neural processes. Alcohol’s short-term effects on brain cells are immediate and multifaceted, primarily due to its role as a central nervous system depressant. When alcohol is consumed, it rapidly crosses the blood-brain barrier, interfering with the delicate balance of neurotransmitters—the brain’s chemical messengers. One of the most direct impacts is on gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter.

To probe impulsiveness through fMRI, response inhibition tasks are commonly used, such as the Go/no-go (GNG) task and Stop Signal Task (SST).
Depolarization and activation of the nerve action potential are maintained by the influx of different types of ions (Na+ and Ca2+) into the cell through the NMDA receptors 58.
However, with timely intervention, abstinence, and supportive lifestyle changes, it is possible to mitigate and even reverse some of the detrimental effects of alcohol on the brain.
Alcohol use in minors has been linked to significant shrinkage of the hippocampus and smaller prefrontal lobes than people of the same age that don’t drink.
Alcohol-related functional differences in the brain are not exclusively observed in dependent individuals.

The impacts of long term and short term alcohol use on cognitive functioning and neurodegeneration can be studied extensively by resting-state fMRI (functional magnetic resonance imaging) and task-based fMRI 69,93. Resting-state fMRI demonstrates the atypical dynamics in severe AUD 94 and task-based fMRI suggests altered neuronal network activity in executive control regions (Basal ganglia, SN) during task performance such as risk-taking, impulse control, and emotional oriented tasks 95,96. It is known that during oxidative stress conditions the levels of oxidants are higher than the levels of antioxidants. So, ethanol indirectly decreases the antioxidant activity by increasing oxidative stress response. Alcohol-induced ROS production is believed to be specific to EtOH metabolism by cytochrome P450–2E1 (CYP2E1), which produces H2O2, superoxide, and free radicals.

Does Alcohol Kill Brain Cells?

In particular, MRI studies of individuals with AUD demonstrate widespread diffuse loss of both cortical white and gray matter thickness where disproportionate deficits of gray and white matter are more visible in older age compared to young patients 86.
Research has found an increased prevalence of AUD and heavy drinking, primarily among women.
Additionally, this protein adduct formation can also induce an immune response which can further damage tissues.
It is also important to note that thiamine absorption in the gut can be altered by several genetic variants that affect thiamine transport and metabolism 69.

Schulte et al. demonstrated cognitive processing disturbance with neuronal desynchronization in adults with AUD in MEG study 100. Accordingly, neuroimaging tools are required to observe the pathological changes and disease progression to figure out an applicable treatment agreement for AUD. There is evidence of gender- and sex-related differences in consumption of alcohol as well as its effects on the brain 153. However, neuroimaging studies on the effects of alcohol use and dependence have either excluded women or shown low female enrolment 154. Consideration of gender- and sex-related effects has also been limited, in part due to a lack of power 154. Rates of alcohol dependence have increased drastically in women and many of the harmful health effects are more severe and occur more rapidly in women 155.

At the lowest tested ethanol concentration of 10 mM, alcohol exposure led to a 6-11% induction in metabolic activity in differentiated cells and 1-10% induction in undifferentiated cells. Alcohol exposure was found to reduce the metabolic activity and viability of both undifferentiated and differentiated cells in a dose- and exposure-duration-dependent manner. A significant reduction in cell viability was observed after six hours of exposure to alcohol concentrations of 20 mM or more. PET studies investigating the serotonin system in alcohol dependence are very limited in number, and so a consensus opinion on their importance has not been reached. Studies have focused on the serotonin transporter (SERT) using 11C DASB, revealing mixed results with some 148,149 reporting increased levels of SERT whereas others have found no difference or reduced levels of SERT 150. Strength of evidence to show direction of effects on receptor radioligand binding in human PET imaging studies in alcohol dependence.

Although alcohol might not cause actual neural death, alcohol misuse can and does lead to brain damage. “Generally, over time, there have been new studies that show that chronic alcohol use — at very heavy use — can lead to brain damage, both gray and white matter. Currently, only five FDA-approved drugs are available to diminish the progression of neurodegenerative conditions. Four of them donepezil, rivastigmine, galantamine, tacrine, are based on acetylcholinesterase inhibition, and one of them, memantine, is an NMDA receptor antagonist 119.

Emerging evidence provides a glimmer of hope, suggesting that the brain possesses a remarkable ability to recover from alcohol-induced damage, a phenomenon known as neuroplasticity. This process involves the brain’s capacity to reorganize itself by forming new neural connections throughout life. When alcohol consumption is reduced or ceased, the brain can begin to repair some of the damage by generating new neurons, a process called neurogenesis, and by strengthening existing neural pathways. For instance, studies on individuals who have abstained from alcohol show significant improvements in brain structure and function, particularly in regions previously affected by alcohol.

Binge drinking

ROS production was significantly higher in differentiated cells as compared to undifferentiated cells. Interestingly, evidence suggests that dysregulation of the reward system in abstinent alcohol-dependent individuals can be ameliorated by pharmacological intervention. For example, naltrexone, a Alcohol and Brain Cells µ-opioid receptor antagonist, can attenuate the increased BOLD response to alcohol-related cues in the putamen and reduce risk of relapse 101. The reduction in cell viability was more pronounced in undifferentiated cells as compared to differentiated cells.

Alcohol interferes with the brain’s communication pathways and can affect the way the brain looks and works. Alcohol makes it harder for the brain areas controlling balance, memory, speech, and judgment to do their jobs, resulting in a higher likelihood of injuries and other negative outcomes. Long-term heavy drinking causes alterations in the neurons, such as reductions in their size.