Does Alcohol Kill Brain Cells? Part One
Does Alcohol Kill Brain Cells? Part One: Post-Mortem Brain Research
By Kenneth Anderson, MA
It is a commonly held belief that alcohol kills brain cells; however, is there any truth to this belief, or is it simply a myth? While it is clear that pathological conditions such as Korsakoff’s syndrome or alcohol-related dementia result in the death of brain cells, these conditions are not due to the direct effect of alcohol.
Therefore, this blog post will not look at pathological conditions such as Korsakoff’s syndrome or alcohol-related dementia which are due to other factors in addition to alcohol, such as nutritional deficiencies. Instead, we will limit our discussion strictly to the direct effects of alcohol on the brain. Korsakoff’s syndrome or alcohol-related dementia are somewhat uncommon and don’t affect most people with AUDs (alcohol use disorders) or who are heavy drinkers. Moreover, Korsakoff’s can be prevented by getting enough thiamine (vitamin B1) in one’s diet. Although brain structural changes caused by Korsakoff’s syndrome or alcohol-related dementia are large and readily seen by the naked eye, changes caused by heavy drinking or simple AUD are small and much like those caused by normal aging. Moreover, there is a huge overlap between the brains of abstainers and those of drinkers, meaning that the differences between the two are only statistical; the differences cannot be found by comparing a single brain of a person with AUD with a single brain of an abstainer. Many brains of people with AUD must be compared with many brains of abstainers in order to identify a statistical difference between the two groups.
The normal aging process results in neuron death, brain shrinkage, and reductions in cognitive functions in healthy brains. Brain volume decreases with age at an estimated rate of 0.19% per year, i.e., 1.9% per decade. Brain shrinkage is also the result of heavy drinking or simple AUD. What we need to tease out is whether the direct effect of alcohol increases neuron death, brain shrinkage, and reductions in cognitive functions over and above the effects of normal aging. We also must be cautious about making any generalizations from clinical samples of people in treatment for AUD and applying these generalizations to people with AUD in community samples, since it is a fact well-known to epidemiologists that clinical samples always show far greater severity than community samples, so this should be borne in mind while reviewing the research.
How Do We Know Whether Alcohol Kills Brain Cells?
It is well established that long-term heavy drinking leads to shrinkage of the brain, particularly the white matter, and that long-term abstinence from alcohol or moderation reverses this shrinkage, at least to a large degree. This shrinkage is accompanied by cognitive impairment, which also abates with long-term abstinence or moderation. However, before we investigate theories of why this happens, let’s first have a brief review of the structure and function of the brain.
Structure and Function of the Brain
The surface of the cerebrum is known as the neocortex. The neocortex is comprised of gray matter and is about two millimeters (mm) to four mm (0.08 inches to 0.16 inches) thick. Gray matter is comprised of the cell bodies of neurons, dendrites, some short unmyelinated axons, and some supporting tissue. Neurons in the neocortex consist of a cell body, several dendrites which function as inputs, and a single axon, which serves as an output. For some neurons, this axon stays within the neocortex and has no myelin sheath. For other neurons, this axon travels outside the neocortex toward the center of the brain. These latter axons are sheathed in myelin and make up the white matter of the brain.
Myelin is a white, fat-like substance which acts as an electrical insulator. Myelin sheaths surround axons, much like insulation surrounds an electrical wire. As noted above, not every axon has a myelin sheath. Short axons which remain inside the gray matter have no myelin sheath and are known as unmyelinated axons. Long axons which project out of the gray matter and send information to other parts of the brain have myelin sheaths and are known as myelinated axons. Myelin insulation is necessary on long axons to prevent the electrical signal from disappearing; they also supply food, etc. to the axon. The white matter of the brain is comprised of myelinated axons which have their cell bodies in the gray matter or in certain nuclei. Cell bodies of neurons are not found in the white matter.
Another brain structure which is important to the discussion of alcohol’s effect on the brain is the hippocampus, which lies deep within the brain. There are actually two hippocampi, one on the left side of the brain, and one on the right. The hippocampus is made up of gray matter consisting of cell bodies, dendrites, short unmyelinated axons, and some supporting tissue. Myelinated axons (i.e., white matter) project out from the hippocampus to send signals to the other parts of the brain. The hippocampus is the seat of memory.
What Rodent Studies Tell Us About Alcohol and the Human Brain
Rodent studies tell us very little about the neurotoxic effects of alcohol in human brains, because rodent brains react very differently to the neurotoxic effects of alcohol than human brains do. As Crews and Nixon 2009 point out, intoxicating doses of alcohol readily kill brains cells in rodents. However, the brains of adult rodents can readily create new brain cells; this process is known as adult neurogenesis. During a period of abstinence from alcohol, new brain cells appear in the adult rodents which can replace those killed by alcohol. This is how adult rodents recover cognitive abilities which have been impaired by alcohol.
In humans, however, adult neurogenesis is either absent or very minimal; it is still a matter of debate whether it is totally absent or near totally absent. Adult humans essentially cannot replace neurons when these cells die. However, in adult humans, as I will describe, intoxicating doses of alcohol either fail to kill brain cells or they kill very few brain cells in limited areas; this is still somewhat of a topic of debate.
So, Does Alcohol Kill Brain Cells in Humans? Post-Mortem Science Gets Us Closer to the Answer
Jensen and Pakkenberg (1993) conducted one of the first studies which attempted to actually count the number of neurons of the brains of people with alcohol use disorder (AUD) and compare them to control brains. The researchers compared the brains of 11 deceased men with alcohol dependence as defined by the DSM-III-R to those of 11 deceased men without alcohol dependence. Subjects were matched for age and height. It was found that the AUD brains had an average of 23.4 billion neurons in the neocortex, and the control brains had an average of 23.2 billion neurons in the neocortex. This difference was not statistically significant. However, the AUD brains had an average of 11% (volume weight ratio) less white matter than the control brains, which was significant. The hippocampus of the AUD brains also showed a 30% volume/weight reduction compared to the control brains; this difference was also significant.
The Jensen and Pakkenberg study looked at very broad areas of the neocortex. A 1997 study by Kril et al., however, looked at very specific areas of the neocortex of deceased subjects to see if there was neuron loss in any specific area. The researchers compared the brains of six people with simple alcohol dependence, four with Korsakoff syndrome, and four with Wernicke’s encephalopathy with 21 control brains. Subjects with AUD had consumed more than 80 grams of alcohol (5.7 US standard drinks) per day for at least 20 years. Subjects without AUD had consumed less than 20 grams of alcohol (1.4 US standard drinks) per day; in fact, most were nondrinkers. Subjects with simple alcohol dependence showed a 23% loss of neurons in the frontal association area of the neocortex; this was a statistically significant difference. The frontal association area is involved in thinking, planning, emotional regulation, etc.
Harding et al. (1997) conducted a study of the brains of deceased subjects to determine the effects of alcohol consumption on the hippocampus. Five of the brains studied had had AUD with Korsakoff’s syndrome, seven brains had had AUD without Korsakoff’s syndrome (three of these had had Wernicke’s encephalopathy but no amnesia), four brains had had Alzheimer’s, and eight brains were controls. Subjects with AUD had consumed more than 80 grams of alcohol (5.7 US standard drinks) per day for at least 20 years. Subjects without AUD had consumed less than 20 grams of alcohol (1.4 US standard drinks) per day, in fact, most were nondrinkers. The hippocampi of the subjects with AUD, whether they had Korsakoff’s syndrome or not, showed no loss of neurons compared to the control group. The hippocampi of the subjects with Alzheimer’s, on the other hand, showed significant loss of neurons compared to the control group. However, the white matter of the hippocampi of the AUD brains showed significant shrinkage compared to the hippocampi of the control group. Interestingly, the white matter of the hippocampi of the AUD brains showed significant shrinkage only for the subjects who were actively drinking at the time of death; those who had been abstinent for a long period prior to death did not show significant shrinkage, which suggests that white matter returns to normal with abstinence. Numerous other studies have shown a reversal of white matter shrinkage throughout the brain as a result of long-term abstinence or moderation.
Harper and Corbett (1990) conducted a study of the effect of alcohol on the dendrites of the neurons in the neocortex using the brains of 15 deceased males with AUD and 15 deceased male-matched controls. AUD subjects had consumed an average of 120 grams of alcohol (8.6 US standard drinks) per day; the control subjects had consumed less than 20 grams of alcohol (1.4 US standard drinks) per day, and five were nondrinkers. Neurons in the neocortex of the AUD brains showed a significant loss of dendrites compared to the control brains.
It is well established that abstinence from alcohol reverses white matter shrinkage in the brain in the case of simple AUD. Two hypotheses for white matter shrinkage and its reversal have been put forth: the first hypothesis assumes that the shrinkage and its reversal are the result of dehydration and rehydration; the second hypothesis assumes that this is a result of loss of myelin (demyelination) and regrowth of myelin (remyelination). Mann et al. (1993) tested the first hypothesis by using CT scans to measure the amount of water in the brain. The researchers found no evidence of dehydration and rehydration and concluded that demyelination and remyelination was the most likely explanation. A third explanation for brain shrinkage and its reversal in AUD was put forth by Trabert et al. (1995), who hypothesized that the shrinkage was due to reduced cerebral blood flow, and that its reversal was due to the restoration of cerebral blood flow. However, this explanation has not been accepted, since the regions with reduced blood flow do not necessarily correspond to the areas showing shrinkage. However, most researchers believe that changes in cerebral blood flow may be a contributing factor to brain shrinkage and cognitive deficits resulting from AUD–just not the entire cause. Current researchers also believe that changes in the number of glial cells can contribute to brain shrinkage and its reversal. Glial cells operate as a support system for neurons.
A large body of research (e.g., Fein et al., 1990, 2006) shows that cognitive impairments which result from simple AUD disappear and cognitive functioning returns to normal after an extended period of abstinence or moderate drinking. The evidence suggests that this is a result of remyelination of axons which reverses the shrinkage of the white matter, and a result of regrowth of dendrites which restores function in gray matter. In fact, a rodent study by Navarro and Mandyam (2015) shows remyelination of axons and a regrowth of dendrites in rodent brains after a period of abstinence from alcohol. A 2001 study by Estilaei et al. also suggests that remyelination of axons and a regrowth of dendrites is a result of abstinence from alcohol in human brains. Even if some neurons are lost in the frontal association cortex, it is possible that their functions could be taken over by new networks of dendrites and axons.
This completes part one of this blog post, which looks at the studies of the brains of dead people to help answer the question, “Does alcohol kill brain cells? Part two will look at alcohol and the brains of living people in community samples. Part three will look at clinical samples.
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