Alzheimer's disease affects 5 million Americans, most of whom will be in nursing homes for some part of the 10 to 20 years they may live with the illness.

The cost of caring for these patients, as well as the emotional and financial toll on their caregivers, who are usually family members, all have a devastating effect on society, says a pioneering researcher into the mechanisms involved in the progression of Alzheimer's.
W. Sue T. Griffin, PhD, a professor and vice chairman for research in the Donald W. Reynolds Department of Geriatrics at the University of Arkansas for Medical Sciences, reported in 1989 that decreasing neuroinflammation was a key factor in delaying the onset or progression of the disease.

This idea wasn't well-received at the time, said Griffin, who is also co-editor-in-chief of the Journal of Neuroinflammation. But today, "pretty much everyone accepts that neuroinflammation is important in this disease process."

Now, a new finding by her and her team of researchers could play a major role in the development of better treatments to slow the deterioration of cognitive functioning in Alzheimer's patients. She has discovered a link between an excess of Interleukin-1, a cytokine or protein produced by the immune system that can cause inflammation, and the increased probability of onset of Alzheimer's.

"Where our work comes in is decreasing the inflammation in the brain," she said. Interleukin-1 "acts as a driver for the further destruction of the nerve cells. It can sometimes be repaired, but in Alzheimer's, it's an ongoing event, and what happens then is there's so much of the cytokines there, it causes an increase in the protein that's the precursor for the amyloid in the plaque" that injures neurons.

"Over time, because the disease is chronic, you have a vicious circle of neuron degeneration, caused by the overexpression of Interleukin-1."

By finding a way to interrupt that cycle, "we could delay the onset of Alzheimer's, and if we could delay it by, say, five years, it would have a tremendous effect on the cost of the disease," said Griffin.

 

There are only a couple of drugs on the market to treat Alzheimer's, Griffin points out, and "neither one works very well. They don't block the progression" of the disease, she said.

Some encouraging results have come from studies of the effect of NSAIDS on inflammation, she said. Griffin cites one study done with veterans who took ibuprofen daily over relatively short periods for conditions such as rheumatoid arthritis. The study found that taking ibuprofen for five years cut the incidence of onset of Alzheimer's in half.

While genetics do play a role in whether or not a person will develop Alzheimer's, Griffin said only about 5 percent of cases can be attributed to genetic factors.

Much of a person's risk of developing Alzheimer's or other forms of dementia involves lifestyle, she said. Animal studies have shown that exercise affects factors in the brain that promote nerve-cell health, and exercise also has a beneficial effect on risk-enhancing factors like diabetes, obesity and heart disease that compromise the flow of blood and oxygen to the brain.

Diet also is important in maintaining brain-cell health, she said.

"So all these things together mean we're supposed to take care of our bodies. We're supposed to eat right and exercise according to what we do in our daily life," according to Griffin.

 

Jeanne Wei, MD, PhD, director of the Reynolds Institute on Aging and chairman and professor of the Department of Geriatrics, agrees with Griffin's remarks on the benefits of exercise and proper nutrition.

"We have several studies where we're trying to understand better what allows people to maintain function, both physical and cognitive," Wei said. "So what we're finding, for example, is that exercise conditioning is very good for maintaining not only muscle strength but also cognitive function.

"On the one hand, many of us would rather there were a pill we could take, but on the other hand, we know that within each one of us is the power to take control of maintaining our own cognitive function.

"There are some possibilities (for treatment) on the horizon that people are looking at, but few have as much power or few side effects as exercise," she said.

In addition to diet and exercise, having a positive outlook helps maintain cognitive functioning, as does keeping up social relationships. And "combining all three – exercise, outlook and social connectedness – help reduce the level of inflammation," Wei said.

"It is this kind of research that informs us so we can develop better targets for therapy in the future. By better, I mean that will have fewer side effects and be more effective."
The goal, Wei said, is to intervene earlier in the disease process in order to prevent further decline or even reverse mild decline.