Uncontrolled blood sugar may affect cognition and the brain years before dementia symptoms arise Two recent studies show blood-sugar levels can affect the brain—-adding new evidence that diabetes might be a significant risk factor for developing Alzheimer’s disease and other forms of dementia.
Researchers at Washington University in St. Louis found in a study of mice that raising blood sugar to abnormally high levels corresponded with increased production in the brain of amyloid beta, a protein thought to be an important factor in Alzheimer’s disease. In a separate study of middle-aged people, conducted at the University of Pittsburgh, those with Type 1 diabetes had significantly more brain lesions, and slower cognitive function, than people without the disease.
Neither study is definitive, and more research is needed. Still, doctors say the results underscore the need for people with diabetes to closely control their blood sugar and keep it within healthy ranges.
For people with Type 2 diabetes, exercise represents a promising way to reduce the risk of Alzheimer’s, says Suzanne Craft, professor of gerontology and geriatric medicine at Wake Forest Baptist Medical Center. Exercise directs the body to more efficiently metabolize insulin. Insulin also is thought to help protect the brain against amyloid and improve connectivity between neurons and memory formation, she says.
Diabetes, a condition where the body is unable to effectively break down blood sugar, affects some 29 million people in the U.S. and can cause heart disease, blindness and death. Type 2 diabetes, the most common form, occurs when the body becomes desensitized to insulin, a naturally occurring hormone that metabolizes sugar. Type 1 diabetes, which typically surfaces during childhood, occurs in people whose bodies don’t produce enough insulin to begin with.
Alzheimer’s disease is still poorly understood and there are multiple risk factors that contribute to dementia, including genetics and age. Most people with diabetes won’t go on to develop Alzheimer’s disease and are able to live healthy, fully functional lives.
“If we prematurely equate diabetes with a condition as severe as dementia or Alzheimer’s, we’d be doing a great disservice to the 29 million people in this country who hold complex positions and fulfill complex job requirements,” says Samuel Dagogo-Jack, a diabetes specialist and professor of medicine at the University of Tennessee Health Science Center.
The University of Pittsburgh study, of roughly 180 middle-aged people, found that Type 1 diabetics had significantly more brain lesions called white matter hyperintensities than people without diabetes, and performed more poorly on cognitive function tests. Caterina Rosano, a lead researcher in the study, said she was surprised by the findings because the study participants were so young: The diabetic group had an average age of 50 and the nondiabetic group had an average of 48, suggesting uncontrolled blood sugar is having a negative impact on the brain years or even decades before symptoms of dementia start to appear.
“The clinical impact is huge over time,” says Dr. Rosano, associate professor of epidemiology at the University of Pittsburgh’s Graduate School of Public Health. “These abnormalities will impact the speed with which your brain works, and how quickly information travels from one part of your brain to another.” The study was published online in April in the journal Neurology.
In the Washington University study of mice, whose brains were genetically engineered to resemble the brains of humans with Alzheimer’s disease, high doses of sugar over several hours resulted in significantly increased levels of amyloid beta in brain cells. The study, published in May in the Journal of Clinical Investigation, also found that older mice with existing amyloid buildup in their brains experienced even greater production of amyloid beta.
The data suggest that blood sugar plays a role in managing amyloid production, with sugar creating excitability in the brain’s neurons that leads to more amyloid being produced, says David Holtzman, an author of the study and professor of neurology at Washington University. The authors also found that opening a protein channel called ATP-sensitive potassium appeared to lower the production of amyloid, which could make it a target for future drug development, Dr. Holtzman says.
“High blood sugar appears to affect the way the brain functions,” Dr. Holtzman says.
The mice study is “highly suggestive” of a relationship between high blood sugar and amyloid plaques, but the results will have to be reproduced in humans to show a definitive link, says University of Tennessee’s Dr. Dagogo-Jack, who also is president of medicine and science at the American Diabetes Association. “These animal studies raise the tantalizing possibility of future discoveries based on these mechanisms that may well lead to treatments or prevention of both conditions,” Dr. Dagogo-Jack said.
Many researchers believe that Type 2 diabetics are more vulnerable to developing Alzheimer’s disease because they suffer from insulin resistance, where cells are unable to use insulin effectively, leading to an accumulation of sugar in the blood. It is thought that the brain also develops insulin resistance, depriving the brain of nutrients from sugar. Dr. Craft is currently conducting a study to see if inhaled insulin can improve memory in patients with early Alzheimer’s disease. A National Institutes of Health study, meanwhile, is examining the impact of the drug exenatide, which stimulates insulin production, in Alzheimer’s patients.
Michael Gendy, 62 years old, in 2013 enrolled in a study conducted out of Wake Forest examining the effect of regular exercise on people with prediabetes and mild memory problems. Mr. Gendy, a retired engineer who works part time as a tax preparer in King, N.C., says he has continued to exercise since the study ended last year. Twice a week, he attends fitness classes at his local YMCA, performing cardiovascular exercises in addition to push-ups, squats and carrying small weights.
“I’ve seen some improvement in my memory,” Mr. Gendy says. “I have to dig, but I don’t have to dig as deep” to remember things, he says.
Published: May 25, 2015. By Joseph Walker
Copyright ©2015 Dow Jones & Company, Inc