Sensitivity to Alcohol-Induced Brain Damage

by National Institute of Health

Women are more vulnerable than men to many of the medical consequences of alcohol use. Although research has shown that male alcoholics generally have smaller brain volumes than nonalcoholic males, the few studies that have compared brain structure in alcoholic men and women have had mixed results. To adequately compare brain damage between alcoholic women and men, it is necessary to control for age and to have separate control groups of nonalcoholic men and women. Although the majority of studies suggest that women are more vulnerable to alcohol-induced brain damage than men, the evidence remains inconclusive.

Men and women are affected differently by many diseases, including alcohol-related conditions. For at least a quarter century researchers have recognized that many of the medical consequences of excessive alcohol consumption develop more rapidly among women than among men. For example, alcoholic women develop cirrhosis, alcohol-induced weakening of the heart muscle, and nerve damage in the body's extremities (peripheral neuropathy) after fewer years of heavy drinking than alcoholic men. Studies comparing men's and women's sensitivity to alcohol-induced brain damage, however, have yielded inconsistent results. This article reviews the research and the factors other than alcoholism that can affect gender-based comparisons of brain structure.

Male and Female Vulnerability to Alcohol-Induced Brain Damage

As reviewed in this issue of Alcohol Research & Health many studies have found small but usually statistically significant differences in the brain volumes of male alcoholics compared with those of nonalcoholics. In contrast, few studies have directly compared brain structure between alcoholic men and alcoholic women. Two early computerized tomography studies compared brain shrinkage, a common marker of brain damage, in alcoholic men and women by measuring the increase in the fluid surrounding the brain, which is an indication of the size of the lateral ventricle (a CSF-filled cavity inside the brain that increases in size as the brain shrinks).

Both studies reported that male and female alcoholics had significantly larger amounts of intracranial CSF than control subjects did, indicating greater brain shrinkage among alcoholics of both genders; alcoholic women also reported about half as many years of excessive drinking as the alcoholic men. In addition to this evidence for excessive brain shrinkage among alcoholic women, there is also evidence that the degree of cognitive dysfunction in alcoholic women is similar to that in alcoholic men despite fewer years of heavy drinking on the part of the women. These results suggested that the central nervous system (CNS) in women, like other organ systems, is more vulnerable to alcohol-induced damage than the CNS in men.

Subsequent studies have not universally confirmed women's greater vulnerability to alcohol-induced brain damage. For example, Kroft and colleagues, using magnetic resonance imaging, failed to detect that the fluid-filled chambers in the brain (cerebral ventricles) were larger in alcoholic women than nonalcoholic women, although other researchers have found MRI evidence for ventricular enlargement among alcoholic men. Two recent reports that appeared side by side in the American Journal of Psychiatry contradicted each other on the question of gender-related vulnerability to brain shrinkage in alcoholism.

It would seem that whether alcoholic women experience greater brain damage than alcoholic men could be determined by comparing the sizes of the brains of alcoholic men and women with the brain sizes of nonalcoholics of each gender. However, details such as how different investigators measure brain size and damage or how they select alcoholic subjects may make a big difference in the results of each study. Because relatively few studies have compared alcoholic men and women, it is possible to review the measurement methods and population characteristics used in each study to determine if these factors explain the inconsistent results. Before examining these studies on alcoholism, however, it is useful to describe factors independent of alcoholism, such as age, that affect gender differences in brain structure.

Factors Affecting Gender-Based Differences in Brain Structure

Women have smaller bodies than men, and this difference in body size extends to the head, skull, and brain. Most of the difference in intracranial volume (a measure of the maximum size to which the brain grows) between healthy nonalcoholic women and men is explained by height. However, several studies have shown that even when height is taken into account, women still have smaller brains than men.

In addition to height, age is another factor influencing brain size. The amount that the brain shrinks with age can be measured by examining the ratio of brain volume to intracranial volume. In this way, brain shrinkage can be measured independent of the initial size of the brain. Among both men and women the ratio of brain volume to intracranial volume decreases with age. Several researchers have reported that the rate of brain shrinkage during aging may be slightly higher among men.

Some investigators have found that women's proportion of gray matter appears to be slightly, but significantly, greater than men's. Other researchers have suggested that this difference is secondary to overall brain size and not specifically related to gender. Among healthy nonalcoholic control subjects, women have proportionally more gray matter than men; it also appears that the proportion of the inside of the skull occupied by gray matter decreases with aging similarly in men and women. However, analyses of gray-matter volume were conducted to remove the influence of overall brain size, the differences in gray matter between the genders were no longer significant. This suggests that the greater proportion of gray matter observed among women is caused by differences in brain size between men and women and not by gender itself.

The results indicate that to adequately compare brain damage between alcoholic women and men, researchers should control for age and have separate control groups of nonalcoholic women and men. Separate control groups are needed, for example, because differences in height account for most of the difference in brain size between men and women. Controlling for the amount of lifetime alcohol consumption also is necessary because several studies have shown that alcohol consumption, independent of age, predicts brain shrinkage.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.