Looking at the link between diabetes and dementia

Two of the most worrisome trends in healthcare — the soaring rates of Type 2 diabetes and dementia — share several key biological processes. And scientists are beginning to think that is more than just a coincidence.

Many researchers now believe that proper control of blood sugar could pay dividends in the future by reducing the number of people stricken by Alzheimer’s disease, other forms of dementia and even the normal cognitive decline that comes with age.

The concept that brain diseases share little in common with diseases arising elsewhere in the body is rapidly crumbling, says Debra Cherry, executive vice president of the Alzheimer’s Assn. California Southland. The key characteristics found in the development of heart disease and stroke — clogged arteries and inflammation in cells — also affect the brain.


On the flip side, she adds, “what is good for the reduction of diabetes risk is also good for reduction of the risk of cognitive impairment.”

About 6.8 million people in the U.S. have some type of dementia. Alzheimer’s disease is the most common, affecting 5.4 million people, a number that is projected to double by 2040, according to the Alzheimer’s Assn. The cause of Alzheimer’s is unknown, although studies show people with the disease have higher concentrations of clumps made up of a protein called beta amyloid in their brains. There are no treatments to slow or stop the disease process.

More than 8% of American adults and children have either Type 1 or Type 2 diabetes, a number that is expected to grow in conjunction with the rise in rates of obesity, which is a risk factor for the Type 2 form of the disease. Diabetes is diagnosed when the body can’t produce enough insulin or use insulin properly to remove sugar from the bloodstream. When blood sugar remains too high, it can damage organs and lead to heart disease, kidney failure, nerve damage and many other complications. There are medications to lower blood sugar, and in severe cases, people with diabetes must take insulin.

Type 1 diabetes is usually diagnosed in childhood and requires insulin, while Type 2 typically involves weight gain in adulthood. But both diseases could affect cognitive health later in life.

The relationship between diabetes and dementia diseases drew headlines in September when a large study conducted in Japan reported that people with diabetes are twice as likely to develop Alzheimer’s disease. The study, published in the journal Neurology, found that even people with impaired glucose tolerance — a level of poor glucose control that precedes diabetes — were 35% more likely to develop some type of dementia.

An estimated 1 in 10 cases of dementia may be attributable to diabetes, says neurologist Dr. Geert Jan Biessels of Utrecht University in the Netherlands and a leading researcher on the relationship between the two diseases. These disorders may contribute to dementia decades before symptoms such as memory loss occur. Thus, he says, treating diabetes and the risk factors associated with it — such as hypertension and high cholesterol — may help prevent many dementia cases.

The disheartening failure in recent years to find effective treatments for Alzheimer’s disease has caused researchers to look with extra interest at the link to diabetes and other diseases such as heart disease and stroke.

“We want to find ways of intervening before people develop cognitive impairment and dementia,” says Dr. Denise G. Feil, a geriatric psychiatrist and clinical researcher at the VA Greater Los Angeles Healthcare System.

The association between the two disorders is complicated, however. Researchers are exploring two general avenues: One has to do with vascular disease and the other with blood sugar control.

The fact that vascular disease can lead to dementia has been known for some time. Damage to blood vessels in the brain in the form of mini-strokes that decrease blood flow and kill cells can cause so-called vascular dementia —and diabetes is one of the illnesses that can accelerate this type of brain injury.

Alzheimer’s disease is different: It involves a buildup of amyloid plaque in the brain. But diabetes appears to play a role in that process too. Some researchers believe that poor blood sugar control can make it harder for the body to clear away amyloid. Others suspect that high levels of glucose create a kind of toxicity in the body related to oxidative stress, in which harmful free radical molecules build up and damage tissue.

Free radicals are primed to react chemically with any other molecules they hit. “They bang into other molecules, causing inflammation,” Cherry says. “Amyloid plaque may be a result of inflammation, at least in part. “

Genetics also shows a link between the two diseases. People with a mutation known as ApoE4, who are known to have a higher risk for Alzheimer’s disease, also have an increased risk of diabetes.

Still, trying to prevent dementia by treating diabetes is not an easy matter. Two important studies published in 2008 showed that strict control of blood sugar raised the risk of severe hypoglycemia — a condition in which blood sugar drops too low — that can lead to seizures, coma or death.

And neither the large-scale ACCORD trial (the Action to Control Cardiovascular Risk in Diabetes) nor the ADVANCE trial (Action in Diabetes and Vascular Disease) showed any benefits in reducing heart attacks, strokes or deaths from therapy that kept blood glucose levels very low.

Moreover, tight glucose control raised the risk for hypoglycemia especially in the most vulnerable patients, such as people who already had some cognitive impairment, Feil says.

“We now know these are bad outcomes in these populations,” she says. “We’re over-treating without conferring any benefits. There is no balance there.”

Feil and her colleagues conducted yet another study of about 500,000 older veterans. The data, presented in April at a meeting of the American Assn. for Geriatric Psychiatry, showed that those who had cognitive impairment or dementia seemed to be at higher risk for hypoglycemia, especially if they were taking insulin — further suggesting that tight glucose control is not a good option for such patients.

Though the failure of ACCORD and ADVANCE to prevent vascular damage due to diabetes disappointed many, it hasn’t extinguished interest in the topic.

One new study indicates that controlling diabetes more gently can help. Researchers at Columbia University examined 2,169 people ages 55 and older with Type 2 diabetes. Those who receive education to better control their diabetes — within the established guidelines for normal diabetes control, not hyper-aggressively as was done in ACCORD and ADVANCE — had better blood sugar control and slower cognitive decline compared with those who did not have the intervention. The study was published in June in the Journal of Nutrition, Health and Aging.

And a small pilot study of 104 diabetes-free adults with early-stage Alzheimer’s disease, conducted by scientists at the Veterans Puget Sound Health Care System in Seattle, found that treatment with an insulin nasal spray improved symptoms of memory loss over a period of six months. The study, published in September in the Archives of Neurology, also found that participants who got a higher dose of insulin or a placebo had no change in their memory abilities.

Though the effect of diabetes management on dementia risk is still uncertain, it’s clear that a healthful diet, exercise and maintaining proper blood sugar levels will lower the risk of many disorders associated with diabetes, Cherry says.

Regular moderate exercise can reduce the risk of diabetes by half, she says. Moreover, efforts to reduce abdominal fat may reduce the rate of cognitive decline, since carrying significant belly fat raises the risk of late-onset Alzheimer’s disease in both middle-aged and elderly people, according to a study published online in June in the journal Alzheimer’s Disease and Associated Disorders.

People with diabetes or pre-diabetes should work closely with their doctors to identify a blood-sugar level that is healthful and achievable, Feil says.

In the meantime, scientists will continue to seek remedies for two major diseases that appear to be bound tightly together.

“People who have diabetes and cognitive impairment or Alzheimer’s disease cost 2.5 times more to the healthcare system,” Cherry says. “If we look at our population and note that in less than 20 years the number of people with Alzheimer’s disease is going to double, that is really frightening.”