The Neurotoxicity of Alcohol
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Chapter 2: Alcohol and the Brain: Neuroscience and Neurobehavior The Neurotoxicity of Alcohol The brain is a major target for the actions of Neuropathologic Changes alcohol, and heavy alcohol consumption has long been associated with brain damage. Studies The brain contains as many as 1 trillion nerve clearly indicate that alcohol is neurotoxic, with cells, or neurons. They come in a variety of direct effects on nerve cells. Chronic alcohol shapes and sizes, some looking like old oak trees abusers are at additional risk for brain injury and others like weather balloons. Many of these from related causes, such as poor nutrition, liver cells project into other brain areas where they disease, and head trauma. regulate the activity of those areas, thereby affecting thoughts, consciousness, decisions, The potential cost to society of alcohol-induced mood, and attention. For every nerve cell in the brain damage is enormous. Approximately brain that is actively engaged in such things as 14 million Americans—about 7.4 percent of the thoughts, emotions, and movements, there are adult population—meet the diagnostic criteria for 10 other cells, called glia, that provide important alcohol abuse or alcoholism (Grant et al. 1994). support to nerve cells. Both of these cell types On any given day, more than 700,000 people in are damaged by chronic alcohol abuse. Loss of a the United States receive alcoholism treatment in critical few due to alcohol-induced brain damage either inpatient or outpatient settings (National may have subtle but important effects on Institute on Alcohol Abuse and Alcoholism decision-making processes, mood, and behavior. [NIAAA] 1997). Approximately 9 percent of alcohol-dependent individuals have clinically There appears to be a continuum of brain damage diagnosable brain disorders (Eckardt and Martin in long-term alcoholics, progressing from mod- 1986). Indeed, alcoholic dementia is the second- erate deficits in the majority of long-term alcohol leading cause of adult dementia in the United abusers to the severe psychosis of Wernicke- States, accounting for 10 percent of cases (Eckardt Korsakoff syndrome (Butterworth 1995; Pfeffer- and Martin 1986). It is exceeded only by baum et al. 1996). This syndrome includes Alzheimer’s disease. Many studies report that Wernicke’s encephalopathy and Korsakoff’s 50 to 75 percent of detoxified long-term alcohol- psychosis, also called Korsakoff’s amnestic dependent individuals show some degree of syndrome. Wernicke’s encephalopathy is cognitive impairment (Eckardt and Martin 1986), associated with thiamine deficiency resulting suggesting that brain dysfunction may persist from malnutrition. Prompt treatment with even after the individual has stopped drinking. massive doses of thiamine may improve symptoms of this disorder, which include Individual susceptibility to alcohol-induced brain confusion, ataxia (disordered gait), and visual damage is highly variable and is related to many abnormalities. Patients have characteristic factors, such as gender, genetics, environment, brain lesions that may be detected by magnetic and sociodemographics (Dufour 1993). Suscepti- resonance imaging (MRI). Korsakoff’s psychosis bility to alcohol dependence is similarly variable; is characterized by anterograde amnesia, where some people become dependent at much lower the individual is unable to retain new information levels of consumption than others do. Therefore, (Eckardt et al. 1981). For example, the patient it is difficult to specify the levels of alcohol views as total strangers people who were encoun- consumption that are likely to lead to alcohol- tered moments before. The memory dysfunction induced brain damage. There is a serious need correlates with the presence of lesions in the for further research in this area. thalamus, a brain structure involved in the routing of sensory information in the brain 134 The Neurotoxicity of Alcohol Figure 1: Reduced brain mass in alcoholics Axial magnetic resonance images from a healthy 57-year-old man (left) and a 57-year-old man with a history of heavy alcohol consumption (right). Images are courtesy of Dr. Adolf Pfefferbaum. (Victor et al. 1989). Although these two condi- observations are supported by imaging analyses. tions usually occur in sequence, they may exist For example, studies using MRI and computed independently; not all patients with Wernicke’s tomography (CT) show enlargement of the encephalopathy progress to Korsakoff’s psychosis, cerebral ventricles (cavities within the brain and Korsakoff’s psychosis may occur without a that are filled with cerebrospinal fluid) and preceding episode of Wernicke’s encephalopathy. sulci (furrows on the surface of the cerebrum) in most alcoholics. Enlargement of these Extremely heavy alcohol consumption for a structures reflects a shrinkage of brain mass prolonged period is generally required to produce (figure 1), consistent with postmortem studies the most severe organic brain disease. One study that show reduced brain weight in alcoholics. In that compared Wernicke-Korsakoff patients with severe alcoholics, the reductions in weight of the alcoholics who did not have serious neuro- cerebral hemispheres and the cerebellum (a brain psychological deficits found that both age of structure predominantly involved in balance and onset and duration of heavy drinking correlated movement; see figure 2) are significant compared with the development of Korsakoff’s psychosis with nondrinkers and moderate drinkers (Harper (Jacobson 1990). Those with Wernicke-Korsakoff and Kril 1993). The reduced brain mass is syndrome began consuming approximately probably due to a combination of actual loss 12 drinks a day at age 25 and drank at that of nerve cells and reduction in cell size. With level for 27 years. sustained abstinence for 1 to 5 months, the defect begins to disappear. This recovery probably Morphological Changes involves increases in neuronal cell size, number and size of the supporting glial cells, and arbori- Postmortem studies of brain tissue in both zation (branching) of nerve endings (Franke et al. humans and animals suggest that chronic heavy 1997). However, neurons that die are lost forever. alcohol use changes brain structure. These 135 Chapter 2: Alcohol and the Brain: Neuroscience and Neurobehavior Figure 2: Anatomy of the brain Cerebrum Cortex Largest portion of the brain, Outer layer of gray matter covering the including the cerebral surface of the cerebrum and the cerebellum hemispheres (cerebral cortex and basel ganglia); involved in controlling consciousness and Neocortex voluntary processes Outermost portion of the cerebral cortex that contains the most Corpus callosum structurally complex brain tissue A bundle of fibers connecting the brain’s hemispheres Diencephalon Hippocampus • Septal area–related to the Part of the limbic system, which limbic system, which is is involved in emotional aspects involved in emotional of survival behavior; also plays aspects of survival behavior a role in memory • Thalamus–a communication center that Basal ganglia relays information to the A group of structures lying deep cerebral cortex in the brain involved in • Hypothalamus–important in movement and cognition Cerebellum maintaining the body’s Involved in maintenance internal environment, or of posture, balance, and homeostasis, through the coordination receipt of sensory and chemical input Source: Mattson et al. 1994. Data from tissue and quantitative morphometry developed in humans; among its functions, it is (structural) studies demonstrate selective neuronal the center for intellectual capacity.) Alcoholics loss, reduced arborization, and reduction of with severe brain disorders, such as Wernicke- synaptic complexity in specific brain regions of Korsakoff syndrome, show more significant alcoholics. The frontal lobes (of the cerebrum)— reduction in white matter and more extensive whose functions encompass the initiation of brain degeneration than do alcoholics with less motor activity and the integration of behavior, severe disorders. intellect, and emotion—appear to be particularly sensitive to alcohol-induced changes (Jernigan et Investigators have found a 22-percent reduction al. 1991). They show the greatest decrease in in the number of neurons in the superior frontal mass and account for much of the associated cortex and motor cortex of alcoholics compared ventricular enlargement. Both gray matter, which with nonalcoholic controls, but no significant is composed largely of neurons, and white matter, differences in other areas of the cortex (Harper which is composed of myelinated nerve fibers, et al. 1987). Recent studies of alcoholics have appear to be decreased. (The myelin sheath reported a relationship between temporal lobe around nerve fibers facilitates the conduction of shrinkage and a history of alcohol withdrawal nerve impulses.) There appears to be a selective seizures, while frontal lobe shrinkage occurs in loss of white matter, particularly in the frontal alcoholics regardless of their seizure history lobes, but it is uncertain how the observed (Sullivan et al. 1996). A decrease in the amount cellular lesions relate to this loss. One reason of N-acetylaspartate in the frontal lobe, a measure these changes are more evident is the greater of neuron viability, is another indication of fron- proportion of white matter to cortical gray matter tal lobe degeneration in alcoholics (Jagannathan in the frontal regions. (Cortical refers to the et al. 1996). The findings of severe damage to cerebral