The role of thiamine deficiency in alcoholic brain disease

Alcohol Research & Health, Spring, 2003 by Peter R. Martin, Charles K. Singleton, Susanne Hiller-Sturmhofel

Differential Sensitivity of Various Brain Regions

Various brain regions and even different cell types within one brain region may differ in their sensitivity to alcohol-induced damage as well as in their susceptibility to associated problems, including alcohol-related malnutrition (e.g., thiamine deficiency). For example, as mentioned earlier, the cerebellum appears to be particularly sensitive to thiamine deficiency, as indicated by the high frequency of cerebellar degeneration in alcoholics. Autopsy studies have found that a region of the cerebellum known as the anterior superior cerebellar vermis most frequently exhibits alcohol-induced damage (Baker et al. 1999). Additional studies have found that the cerebellar vermis is particularly sensitive to the deleterious effects of thiamine deficiency (Baker et al. 1999; Lavoie and Butterworth 1995; Victor et al. 1989). For example, thiamine deficiency contributes to a reduction in the number and size of a certain cerebellar cell type called Purkinje cells in parts of the cerebellar vermis (Philips et al. 1987).

The sensitivity of the cerebellum to alcohol-related damage was confirmed in a recent study in which investigators used an imaging technique called proton magnetic resonance spectroscopy (proton MRS) to determine the levels of certain molecules (i.e., metabolites) that reflect the functionality of the cells in various brain regions of alcoholics and nonalcoholics. For example, one metabolite reflects nerve cell activity, another metabolite reflects the degradation and formation (i.e., turnover) of cell membrane components, and a third metabolite reflects cellular energy levels. The results of the analyses indicated that these metabolites are significantly reduced in the cerebellum of alcoholics, more so than in another brain region commonly affected by alcohol, the frontal white-matter cortex (Parks et al. 2002). Moreover, only some of these reductions in metabolite levels were reversed when the subjects were tested again after 3 weeks and then 3 months of abstinence. These findings suggest that the cerebellum, in particular the cerebellar vermis, is uniquely sensitive to alcohol's effects, including alcohol-related thiamine deficiency, and therefore may be the initial target of alcohol-related damage.

This hypothesis is consistent with the clinical course of the neurocognitive deficits observed in alcoholics. Networks of nerve cells (i.e., neural pathways) extend from the cerebellum through brain regions called the basal ganglia and thalamus to the frontal lobe. These pathways mediate not only traditional cerebellar functions, such as motor control, but also perceptual-motor tasks, executive functions, and learning and memory, all of which are impaired in alcoholics (see Parks et al. 2002). Accordingly, alcohol-induced damage to the cerebellar vermis could indirectly affect neurocognitive functions attributed to the frontal lobe, even early in the disease process when no cortical damage is detectable, by disrupting the neural pathways connecting the two brain regions. As the alcoholism progresses and alcohol exposure persists, damage to the frontal lobe is also likely to occur, further interfering with the functions of that brain region.