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Alcohol-related brain damage alters both the structure and function of the brain as a result of the direct neurotoxic effects of alcohol intoxication or acute alcohol withdrawal. Increased alcohol intake is associated with damage to brain regions including the frontal lobe, limbic system, and cerebellum, with widespread cerebral atrophy, or brain shrinkage caused by neuron degeneration.

Frontal lobe damage becomes the most prominent as alcoholics age and can lead to impaired neuropsychological performance in areas such as problem solving, good judgement, and goal-directed behaviors. Impaired emotional processing results from damage to the limbic system. This may lead to troubles recognizing emotional facial expressions and “interpreting nonverbal emotional cues".

Binge drinking, or heavy episodic drinking, can lead to damage in the limbic system that occurs after a relatively short period of time. This brain damage increases the risk of dementia and abnormalities in mood and cognitive abilities. Binge drinkers also have an increased risk of developing chronic alcoholism.

Alcoholism is also associated with many other health problems including memory disorders, high blood pressure, muscle weakness, heart problems, anaemia, low immune function, liver disease, disorders of the digestive system, and pancreatic problems. It has also been correlated with depression, unemployment and family problems with an increased risk of domestic abuse.

Parental history of alcoholism and/or binge drinking and gender has an influence on susceptibility to alcohol dependence as higher levels are typically seen in males and in those with a family history.

Prevalence

There are nearly 20 million alcoholics in the United States. In about half, “neuropsychological disabilities can range from mild to severe” with approximately 2 million requiring lifelong care after developing permanent and debilitating conditions. Prolonged alcohol abstinence can lead to an improvement in these disabilities. For those with mild impairments, some improvement has been seen within a year, but this can take much longer in those with higher severity damage.

Impact

Excessive drinking costs the US approximately $250 billion in 2010. These costs broadly included health care, loss productivity, property damage, criminal justice, and motor vehicle crashes. A very large portion of these costs are due to binge drinking. These costs fall on the taxpayers, including non-drinkers.

Excessive alcohol consumption is responsible for approximately 1,500,000 deaths and 51,898,400 potential years of life lost globally in 2010.

Populations at Risk

Adolescents and Genetic Factors

The impulsivity and sensation seeking seen in adolescence may lead to increased alcohol intake and more frequent binge drinking episodes, leaving adolescents particularly at risk for alcoholism. The still developing brain of adolescents is more vulnerable to the damaging neurotoxic and neurodegenerative effects of alcohol. “High impulsivity has [also] been found in families with alcoholism, suggestive of a genetic link. Thus, the genetics of impulsivity overlaps with genetic risks for alcohol use disorder and possibly alcohol neurodegeneration".

There is also a genetic risk for proinflammatory cytokine mediated alcohol-related brain damage. There is evidence that variants of these genes are involved not only in contributing to brain damage but also to impulsivity and alcohol abuse. All three of these genetic traits contribute heavily to an alcohol use disorder.

Neurological Deficits

Brain Anatomy

Alcoholics can typically be divided into two categories, uncomplicated and complicated. Uncomplicated alcoholics do not have nutritional deficiency states or liver disease, but have a reduction in overall brain volume due to white matter cerebral atrophy. The severity of atrophy sustained from alcohol consumption is proportional to the rate and amount of alcohol consumed during a person’s life. Complicated alcoholics may have liver damage that impacts brain structure and function, and/or nutritional deficiencies “that can cause severe brain damage and dysfunction”.

Pathophysiology

Alcoholics often present with decreased brain volume, or cerebral atrophy, due to alcohol induced neurotoxicity. Increased microglia density and expression of proinflammatory cytokines also occur showing evidence of neurodegeneration.^[1] Animal studies find that heavy and regular binge drinking causes neurodegeneration in corticolimbic brain regions areas which are involved in learning and spatial memory. Corticolimbic brain regions affected include the olfactory bulb, piriform cortex, perirhinal cortex, entorhinal cortex, and the hippocampal dentate gyrus. A study in rats found that a heavy 2-day drinking binge caused extensive neurodegeneration in the entorhinal cortex with resultant learning deficits.

brain damage from binge drinking is known to occur, it is unclear how the frequency and length of these drinking sessions impacts brain damage in humans. One study found that humans who drank at least 100 drinks (male) or 80 drinks (female) per month (concentrated to 21 occasions or less per month) throughout a 3-year period had impaired decision making skills compared to non-binge drinkers. In the same study, an MRI brain scan found that levels of N-acetylaspartate (NAA), a metabolite biomarker for neural integrity, was lower in binge drinkers. Additionally, abnormal brain metabolism, a loss of white brain matter in the frontal lobe, and higher parietal gray matter NAA levels were found. This shows a correlation between binge drinking, poor executive functioning, and working memory. A decrease in frontal lobe NAA levels is associated with impaired executive functioning and processing speed in neuro-performance tests.

The volume of the corpus callosum, a large white matter tract that connects the two hemispheres, is shown to decrease with alcohol abuse due to a loss of myelination. This affects the integration between the two cerebral hemispheres and cognitive function. A limited amount of myelin can be restored with alcohol abstinence, leading to transient neurological deficits.

The neurons affected by alcohol abuse in the frontal cortex typically have a large soma, or cell body. This type of neuron is more susceptible to Alzheimer’s Disease and normal aging. Research is still being conducted to determine whether there is a direct link between excessive alcohol consumption and Alzheimer’s Disease.

Alcoholism is frequently associated with cerebellum atrophy in complicated alcoholics. Purkinje cells, the cerebellar output cells, in the vermis are reduced in number by 43%. One of the cerebellum’s functions is to organize higher order functioning of the cerebral cortex. This does not occur with the reduced cerebellar output caused by alcohol abuse. The cerebellum is also responsible for refining crude motor output from the primary motor cortex. When this refinement is missing, symptoms such as unsteadiness and ataxia will occur. A potential cause of chronic alcoholic cerebellar dysfunction is an alteration of GABA-A receptor. This causes an increase in the neurotransmitter GABA in cerebellar purkinje cells, granule cells, and interneurons.

Excitotoxicity and Kindling

Binge drinkers and alcoholics who go through multiple detoxifications show impairments in executive control tasks, showing prefrontal cortex dysfunction. Animal studies show that repeated alcohol withdrawals are associated with an inability to learn new information. Alcohols acute effects on GABAergic enhancement and NMDA suppression causes alcohol induced neurotoxicity and kindling, or worsening of alcohol withdrawal symptoms with each subsequent withdrawal period. This may cause CNS depression leading to a partial acute tolerance to these withdrawal effects. This tolerance is followed by a damaging rebound effect during withdrawal. This rebound causes hyperexcitability of neurotransmission systems. If this hyper-excitability state occurs multiple times, kindling and neurotoxicity can occur leading to increased alcohol-related brain damage. Damaging excitotoxicity may also occur as a result of repeated withdrawals. Similar to people who have been detoxified multiple times from alcohol, binge drinkers show a higher rate of emotional disturbance due to these damaging effects.

Thiamine Deficiency

A nutritional deficiency in thiamine can exacerbate alcohol-related brain damage. There is a genetic component to thiamine deficiency causing malabsorption. More frequently however, thiamine deficiency is caused by excessive alcohol consumption leading to Wernicke’s encephalopathy and Korsakoff’s Syndrome which frequently occur simultaneously, known as Wernicke-Korsakoff syndrome. Lesions, or brain abnormalities, are typically located in the diencephalon which result in anterograde and retrograde amnesia, or memory loss.

Neuroimaging

One method that is used to study the effect alcohol has on the brain and its components is through neuroimaging. There are two main subsections of methods in this field, hemo-dynamic and electromagnetic, each is discussed below. These techniques have allowed scientists to study functional, biochemical, and anatomical changes of the brain due to prolonged alcohol abuse. The precision and ability to repeatedly scan an individual has a variety of benefits for both clinicians and researchers. Neuroimaging can also provide valuable information regarding the risk an individual has for developing alcohol dependence and the efficacy of treatment.

Hemo-dynamic Methods

This type of neuroimaging creates images by observing and recording changes in blood volume, blood flow, blood oxygenation and energy metabolism. Positron emission tomography (PET) and Single-photon emission computed tomography (SPECT) are common hemo-dynamic techniques used. These methods require the injection of a radioactive labeled molecule, such as glucose. The injection of these radioactive materials, albeit minimal still exposes the body to harmful radiation. The patient is then observed while performing a memory task. PET and SPECT studies have confirmed and expanded previous findings that stated the prefrontal regions of the cortex are particularly susceptible to decreased metabolism in alcohol abusing patients.

Other hemo-dynamic methods that are commonly used are Magnetic Resonance Imaging (MRI) and functional Magnetic Resonance Imaging (fMRI). These methods are noninvasive, and has no radioactive risk involved. The fMRI method records the metabolic changes in a particular brain structure or region that is under question. Although the MRI method can clearly distinguish grey matter from white matter, it is unable to detect individual damage to nerve fibers that form the white matter. For this scientists use a MRI derivative technique known as Diffusion Tensor Imaging (DTI) which is able to determine the orientation and integrity of specific nerve pathways. Using this method has confirmed previous studies which concluded that heavy drinking disrupts the microstructure of nerve fibers. Yet another MRI derivative technique, Magnetic Resonance Spectroscopy Imaging (MRSI), can provide further information about the neurochemistry of our brains, and can even detect the distribution of certain metabolites, neurotransmitters, and as it so happens, alcohol.

Parasagittal render of human brain with MRI

Electromagnetic Methods

While the hemo-dynamic methods are effective for observing the spatial and chemical changes in an individual, they are limited when trying to demonstrate the time sequence of these changes. Electromagnetic methods are capable of real time detection of electrical currents in the brain. Electroencephalography (EEG) utilizes small electrodes that are attached to a patient’s scalp, and then the recordings are averaged by a technique known as Event-Related Potentials (ERP) in order to determine the time sequences after a presented stimulus such as a word or image. Another electromagnetic method that is used called Magnetoencephalography (MEG) utilizes sensors in a machine to the measure magnetic field created by the brain’s electrical activity. These techniques are noninvasive and harmless, providing exquisite detail about the order and timing of electrical activity, however, the spatial resolution is poor.

These methods of neuroimaging have provided information that is congruent with previous finding that alcohol has altering effects on multiple levels of one’s nervous system. These effects include impairment of both lower order brain stem functions and higher order functioning such as problem solving. These methods of study have also shown differences in electrical brain activity and responsiveness of healthy individuals compared to alcohol-dependent and different yet from those with a family history of alcoholism. The topic of genetic markers for the predisposition for alcoholism is highly debated in the scientific community.

Man ready for EEG recording

Clinical Applications

Cognitive and functional symptoms from excessive alcohol consumption are caused by decreased volume in the cerebral cortex and cerebellum. Atrophy of these brain regions leads to altered neuronal circuits and therefore functional deficits.  In Korsakoff patients, magnetic resonance imaging (MRI) shows atrophy of the thalamus and mamillary bodies.  Positron Emission Tomography (PET) showed decreased metabolism, and therefore decreased activity in the thalamus and other diencephalon structures. Uncomplicated alcoholics, Chronic Wernicke’s Encephalopathy (WE) and Korsakoff psychosis patients had significant loss in frontal cortical neurons, white matter, hippocampus and the basal forebrain. Additionally uncomplicated alcoholics have shrinkage in raphe neurons, the mamillary bodies, and the thalamus. However, WE and Korsakoff patients had overall more brain volume loss. The degree of atrophy is correlated with the amount of alcohol.

Treatment and Prevention

The effects of alcoholism and Wernicke-Korsakoff syndrome can have drastic effects for the individuals afflicted and their loved ones, however, the treatment options are very limited compared to other ailments. Most patients with alcohol-related cognitive defects experienced improvement of their symptoms over the first two to three months of treatment. Others have said to seen increase in cerebral metabolism as soon as one month after treatment.

Education is the best supported alcoholism prevention method. This consists of providing information about risk factors and mechanisms of actions conducted from studies on alcohol-related brain damage to the public. This would assist patients in rehabilitation, increase treatment efforts, and reduce mortality by influencencing doctors to pay closer attention to the warning signs.