Background

Glucose regulation and the brain

The brain depends on the glucose provided by the circulating blood for 99% of its energy needs. For glucose to be used by the brain or any other organ, it must get from the blood to the cells that need it. The hormone that plays the largest role in getting glucose into cells, and consequently in controlling blood sugar, is insulin, which is produced by the pancreas. People with diabetes have high blood sugar levels because they are unable to mobilize glucose from the blood to the tissues. Some individuals are diabetic because they do not produce adequate levels of insulin, and these individuals need insulin injections to control their blood sugar. However, the bulk of people who develop type 2 diabetes have adequate or even high levels of insulin, but their insulin does not work properly. This is called insulin resistance and individuals with type 2 diabetes represent the extreme of insulin resistance.

As we age, many of us develop varying amounts of insulin resistance and memory problems. We are interested in finding out whether these age-associated memory impairments result from reduction in how much glucose gets into brain cells. With advancing age there is a lessening in the ability of individuals to deal with increased amounts of glucose in the blood, such as those that occur after a large meal. This diminished ability to deal with glucose loads is called impaired glucose tolerance. We are investigating whether individuals that develop cognitive impairment as they age are the ones with higher levels of glucose intolerance or insulin resistance.

Cortisol levels and their impact on glucose and memory

There is evidence that cortisol (the stress hormone), which is produced by a gland on top of the kidneys (suprarenal glands), is in part responsible for regulating the effect of insulin on glucose, especially in the brain. Of great interest to us is the fact that administration of cortisol has been shown to temporarily impair memory, whereas administration of glucose (or insulin) improves it. These antagonistic effects of glucose and cortisol on memory may take place in the hippocampus, a part of the brain key in memory function. This may explain why the administration of cortisol temporarily impairs memory performance. Individuals chronically exposed to high levels of cortisol may damage their hippocampus.

It is very interesting that the hippocampus, which has high concentrations of insulin and cortisol receptors, is among the first brain areas affected in the silent (pre-clinical) stages of Alzheimer's disease.

In conclusion

We are very interested in developing a deeper understanding of the relationships between glucose regulation and cortisol secretion on memory function in aging. If we can demonstrate that the relationships that we have highlighted above are actually important in age-associated memory loss, we would have a powerful rationale for instituting interventions aimed at improving memory based on the improvement of glucose and cortisol control. Our goal is to help individuals optimize their memory function as they age.

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