Alcoholism and the brain: an overview

Alcoholism can affect the brain and behavior in a variety of ways, and multiple factors can influence these effects. A person's susceptibility to alcoholism-related brain damage may be associated with his or her age, gender, drinking history, and nutrition, as well as with the vulnerability of specific brain regions. Investigators use a variety of methods to study alcoholism-related brain damage, including examining brains of deceased patients as well as neuroimaging, a technique that enables researchers to test and observe the living brain and to evaluate structural damage in the brain. KEY WORDS: neurobehavioral theory of AODU (alcohol and other drug use); alcoholic brain syndrome; brain atrophy; neuropsychological assessment; neurotransmission; risk factors; comorbidity; disease susceptibility; neuroimaging; treatment factors; survey of research

The brain, like most body organs, is vulnerable to injury from alcohol consumption. The risk of brain damage and related neurobehavioral deficits varies from person to person. This article reviews the many factors that influence this risk, the techniques used to study the effects of alcoholism on the brain and behavior, and the implications of this research for treatment.

About half of the nearly 20 million alcoholics in the United States seem to be free of cognitive impairments. In the remaining half, however, neuropsychological difficulties can range from mild to severe. For example, up to 2 million alcoholics develop permanent and debilitating conditions that require lifetime custodial care. Examples of such conditions include alcohol-induced persisting amnesic disorder (also called Wernicke-Korsakoff syndrome) and dementia, which seriously affects many mental functions in addition to memory (e.g., language, reasoning, and problem-solving abilities). Most alcoholics with neuropsychological impairments show at least some improvement in brain structure and functioning within a year of abstinence, but some people take much longer. Unfortunately, little is known about the rate and extent to which people recover specific structural and functional processes after they stop drinking. However, research has helped define the various factors that influence a person's risk for experiencing alcoholism-related brain deficits, as the following sections describe.

RISK FACTORS AND COMORBID CONDITIONS THAT INFLUENCE ALCOHOL-RELATED BRAIN DAMAGE

Alcoholism's effects on the brain are diverse and are influenced by a wide range of variables. These include the amount of alcohol consumed, the age at which the person began drinking, and the duration of drinking; the patient's age, level of education, gender, genetic background, and family history of alcoholism; and neuropsychiatric risk factors such as alcohol exposure before birth and general health status. Overall physical and mental health is an important factor because comorbid medical, neurological, and psychiatric conditions can interact to aggravate alcoholism's effects on the brain and behavior. Examples of common comorbid conditions include:

* Medical conditions such as malnutrition and diseases of the liver and the cardiovascular system

* Neurological conditions such as head injury, inflammation of the brain (i.e., encephalopathy), and fetal alcohol syndrome (or fetal alcohol effects)

* Psychiatric conditions such as depression, anxiety, post-traumatic stress disorder, schizophrenia, and the use of other drugs.

These conditions also can contribute to further drinking.

MODELS FOR EXPLAINING ALCOHOL-RELATED BRAIN DAMAGE

Some of the previously mentioned factors that are thought to influence how alcoholism affects the brain and behavior have been developed into specific models or hypotheses to explain the variability in alcoholism-related brain deficits. The accompanying table lists the prevailing models. It should be noted that the models that focus on individual characteristics cannot be totally separated from models that emphasize affected brain systems because all of these factors are interrelated. Several of the models have been evaluated using specialized tests that enable researchers to make inferences about the type and extent of brain abnormalities.

Models Based on Characteristics of Individual Alcoholics

Premature Aging Hypothesis.

According to this hypothesis, alcoholism accelerates natural chronological aging, beginning with the onset of problem drinking.

An alternate version suggests that older patients (age 50 and older) are especially susceptible to the cumulative effects of alcoholism, and aging is accelerated only later in life. The preponderance of scientific evidence suggests that although alcoholism-related brain changes may mimic some of the changes seen in older people, alcoholism does not cause premature aging. Rather, the effects of alcoholism are disproportionately expressed in older alcoholics.

Gender: Although it has been hypothesized that women's brain functioning is more vulnerable to alcoholism than men's, studies of gender differences have not consistently found this to be true, even though women and men metabolize alcohol differently (i.e., women achieve higher blood alcohol contents BAC than men after consuming the same amount of alcohol). However, it is not known whether this comparison between men and women holds among older populations.

Family History. Family history of alcoholism has been found to be important because it can influence such things as tolerance for alcohol and the amount of consumption needed to feel alcohol's effects. Also, studies examining brain functioning in people with and without a positive family history of alcoholism have shown that there are clear differences between the groups on measures of brain electrical activity.

Vitamin Deficiency. Research on malnutrition, a common consequence of poor dietary habits in some alcoholics, indicates that thiamine deficiency (vitamin B) can contribute to damage deep within the brain, leading to severe cognitive deficits. The exact location of the affected parts of the brain and underlying neuropathological mechanisms are still being researche

Models Based on Vulnerable Brain Systems

The outer, convoluted layer of brain tissue, called the cerebral cortex or the gray matter, controls most complex mental activities. Just beneath it are the nerve fibers, called the white matter, that connect different cortical regions and link cortical cells with other structures deep inside the brain (subcortical regions).

Areas of the brain that are especially vulnerable to alcoholism-related damage are the cerebral cortex and subcortical areas such as the limbic system (important for feeling and expressing emotions), the thalamus (important for communication within the brain), the hypothalamus (which releases hormones in response to stress and other stimuli and is involved in basic behavioral and physiological functions), and the basal forebrain (the lower area of the front part of the brain, involved in learning and memory). Another brain structure that has recently been implicated is the cerebellum, situated at the base of the brain, which plays a role in posture and motor coordination and in learning simple tasks.

Alcohol-Related Brain Atrophy.

According to one hypothesis, shrinkage (i.e., atrophy) of the cerebral cortex and white matter, as well as possible atrophy of basal forebrain regions, may result from the neurotoxic effects of alcohol . Furthermore, thiamine deficiency may result in damage to portions of the hypothalamus (perhaps because blood vessels break in that region). According to this hypothesis, alcoholics who are susceptible to alcohol toxicity may develop permanent or transient cognitive deficits associated with brain shrinkage. Those who are susceptible to thiamine deficiency will develop a mild or transient amnesic disorder, with short-term memory loss as the salient feature. Patients with dual vulnerability, those with a combination of alcohol neurotoxicity and thiamine deficiency, will have widespread damage to large regions of the brain, including structures deep within the brain such as the limbic system. These people will exhibit severe short-term memory loss and collateral cognitive impairments.