March 11, 2008
Americans with diabetes are at increased risk for Alzheimer's disease, earlier studies show. Now, scientists studying rodents have linked the learning and memory declines to a stress hormone known as corticosterone. It is similar to the main stress hormone produced in humans, called cortisol.
A new National Institutes of Health study in diabetic rodents finds that increased levels of corticosterone disrupts the hippocampus, the region of the brain responsible for learning and short-term memory. The hormone is produced by the adrenal gland.
When the researchers gave the rodents drugs to reduce levels of the stress hormone, the hippocampus recovered its "plasticity," the ability to build new cells and to compensate for injury and disease.
"This research in animal models is intriguing, suggesting the possibility of novel approaches in preventing and treating cognitive impairment by maintaining normal levels of glucocorticoids [stress hormones]," said Richard J. Hodes, M.D., director of the National Institute on Aging, which funded the study. "Further study will provide a better understanding of the often complex interplay between the nervous system, hormones and cognitive health."
In people, production of the stress hormone cortisol involves a complex feedback loop between the hypothalamus and pituitary gland in the brain and the adrenal gland, located near the kidney. People with poorly controlled diabetes often produce excess cortisol.
To study the interaction between elevated stress hormones and the hippocampus, the researchers tested the cognitive abilities and examined the brain tissue in rats with diabetes. They found that diabetic animals had learning and memory problems when stress hormone levels were high. The stress hormones appeared to impair the ability of the brain to grow new cells and forge connections. Returning the levels to normal, however, reversed the negative impact on the hippocampus and restored learning and memory.
"This advance in our understanding of the physiological changes caused by excessive production of cortisol may eventually play a role in preventing and treating cognitive decline in diabetes," said Dr. Mattson, who heads the National Institute on Aging's Laboratory of Neurosciences, part of the National Institutes of Health.
The findings may also help explain the connection between stress-related mood disorders and diabetes found in human population studies, he noted.
About one in five people over age 65 has Type 2 diabetes, a chronic age-related ailment marked by poor control of blood sugar (glucose). Diabetes is especially common in older people who are overweight, though it is becoming increasingly common in younger persons as well.
Previous research suggests that diabetes may increase Alzheimer's risk through various possible pathways. For example, diabetes damages blood vessels in many parts of the body. It may affect blood vessels in the brain as well, impairing blood flow and damaging critical brain functions, including those involving memory.
Poor control of blood sugar levels by the hormone insulin, a hallmark of diabetes, also affects the brain. For example, scientists at the Fisher Center for Alzheimer's Research at The Rockefeller University produced evidence several years ago suggesting that unregulated insulin may raise levels of beta-amyloid, a toxic protein that builds up in the brains of those with Alzheimer's.
This new research adds another possible culprit to the diabetes-Alzheimer's link: stress hormones that play a critical role in the ability of the brain to function and regenerate.
Your chances of developing Type 2 diabetes can be lessened by lifestyle changes such as exercise and a heart-healthy diet. Many researchers suggest that developing heart-healthy habits may decrease the risk of Alzheimer's disease.
It's also important to note, however, that having diabetes does not mean that you will develop Alzheimer's as you age. Rather, diabetes increases your risk for developing the disease. Similarly, many people who develop Alzheimer's do not have diabetes. There appear to be many risk factors for Alzheimer's disease, including genes, years of formal education, heart disease, strokes, being overweight, and more. Diabetes appears to be one more risk factor for this devastating illness.
Mark Mattson, Ph.D., Alexis M. Stranahan, et al: Nature Neuroscience. Feb. 17, 2008.