Any student of the brain and its anatomy is abundantly aware of the seemingly impossible terminology used to identify each of its hills and valleys-hypothalamus, subiculum, insula, fornix, putamen, and others too numerous to list. Two that are of interest for this discussion are the cuneus and the hippocampus. They are not visible from the surface of the brain, but are tucked safely along its inner surface. Although they are separated geographically, they both participate in a vital mental function-memory. These discrete regions communicate with each other via a deep band of fibers (the long processes called axons that connect nerve cells). Because we use our memory constantly there is never a moment when these nerve cells are inactive. As a matter of fact, the brain constitutes 2% of the body weight and consumes 20% of the energy so, on average, it requires 10X the energy the remainder of the body gets by on.
Glucose is the primary fuel used by nerve cells to produce all this energy. When we notice ourselves becoming hypoglycemic, we sense that our brain is not functioning on all cylinders and experience "brain fog." That is because the brain doesn't really store an appreciable amount of glucose and thus requires a stable continuous supply to get the job done. There are even brain scans that are able to generate pictures demonstrating how much sugar each area of the brain is consuming. This type of scan is called a PET scan (for Positron Emission Tomography). Because of its high metabolic rate, the brain consumes a lot of glucose and this can be seen on a PET scan. Some of you might be aware of the application of PET scans in cancer diagnosis. This is useful because most tumors also burn glucose at a rapid rate and hence are easily identified on PET scans. As chemotherapy attacks the cancer cells, subsequent scans show less glucose being used by the tumors and correlate with less metabolic activity and subsequent shrinkage.
Similar findings can be identified on PET scans as we age. When nerve cells become less efficient at burning glucose, they appear less bright on the scan. This correlates with lower glucose metabolism and impaired function. This is typically identified in the brains of persons with Alzheimer's disease. Initially it develops in localized regions and then as time passes it progresses to involve more and more of the surface of the brain. Often the first symptoms noticed have to do with a declining memory. For this reason it is no surprise that PET scans show a fall in glucose metabolism in the areas comprising the cuneus and hippocampus. This radiologic finding is one method used to confirm the diagnosis of Alzheimer's disease.
An illuminating paper on this topic was published in the Proceedings of the National Academy of Sciences (Volume 101, Number 1, pages 284-289) wherein the researchers used this imaging technique to study the brains of mentally normal, healthy middle-aged persons ranging in age from 20-39 years. The common factor shared by each of the subjects was the possession of one copy of a certain gene (or more precisely, allele) called the APO E epsilon 4 allele. This is a risk factor for the development of Alzheimer's disease.
When the brains of these subjects were scanned, the results were remarkable. As a group, they had a lower glucose metabolic rate in the identical regions that are identified early on during the course of Alzheimer's disease, although not as severe. Since this usually is seen in people who are in their mid-seventies, it was surprising to find the same, albeit milder, findings in asymptomatic subjects who were more than 40 years younger. As far as I am aware, this is the earliest abnormality able to predict the subsequent development of Alzheimer's.
As such, it provides evidence that the development of the disorder starts early in life and progresses slowly over decades. It also gives us a protracted window of time to be proactive in slowing down or even preventing it. Just as heart disease has risk factors that are able to be modified, so does memory loss and neurodegeneration. In this instance, impaired ability of the brain to use glucose is the risk factor. This has been referred to as Type III diabetes by various neuroscientists and researchers in the arena of brain health. The similarities between Type II diabetes (usually referred to as adult-onset diabetes) and the brain condition referred to as Type III diabetes are remarkable. They are both metabolic disorders having to do with abnormalities of glucose metabolism, which is something we have a great deal of control over. I will discuss what this means and why it is important in the next article.