The death in June 2004 of former president Ronald Reagan from Alzheimer’s disease (AD) served as a poignant bookend to his announcement nearly 10 years earlier that he had the disease. Reagan’s decade-long, very public battle with AD helped energize the search for effective treatment and prevention strategies.

Alzheimer’s disease currently affects more than 5 million Americans -- a number expected to quadruple in the next 50 years. “Alzheimer’s is a progressive brain disease that affects all demographic groups in our society," says Kathleen Welsh-Bohmer, PhD, director of the Joseph and Kathleen Bryan Alzheimer's Disease Research Center (Bryan ADRC) at Duke.

"It is a major public health menace as our population ages, and it is not part of normal aging," she continues. "In fact, AD is so common as we get older that almost all of us are at risk for developing the condition ourselves -- or seeing someone we love get it.”

The genetic component of that risk has been the subject of intensive research at the Bryan ADRC and Duke’s Center for Human Genetics for more than a decade. Together, investigative teams from the centers identified APOE4, a major susceptibility gene that triples an individual’s risk for developing Alzheimer’s.

Since then, they have gone on to discover several other genes that increase the risk of developing the disease or determine the age of onset. Working now with investigators in the Institute of Genome Science and Policy (IGSP), they have begun expanded studies to discover other genes involved in Alzheimer's disease progression and their significance in the cascade of brain events that leads to the devastating symptoms of memory loss and eventual dementia.

P. Murali Doraiswamy, MD, head of Duke’s division of biological psychiatry, has been working with Duke radiologist Jeffrey Petrella, MD, and Bryan ADRC neuropsychologist Jeffrey Browndyke, PhD, to study the brain function of people who, due to family histories or symptoms of mild cognitive disorder, are at risk for AD. Using a new type of magnetic resonance imaging called functional MRI, they may be able to distinguish between normal brain activity and that found in AD long before the structural changes associated with Alzheimer’s are evident.

“Our goal is to be able to identify people with early Alzheimer’s by a combination of imaging and genetic tests, begin early interventions to slow the progress of AD, and then continue to monitor them with imaging,” Doraiswamy says.

Currently, four medications have been approved by the FDA to treat AD -- and more are on the horizon. “Some of the new compounds that we’re excited about seem to help prevent the formation of the amyloid plaques within brain tissues that are associated with Alzheimer’s,” Doraiswamy says. “Others destroy the plaques’ chemical bonds or inhibit the enzymes that cause them.

“The idea of prevention through delay has become a key concept,” Doraiswamy adds. “If we manage to delay the onset of Alzheimer’s long enough, it will serve in effect as a cure, since people would get through their lives without developing symptoms.”

Amid promising progress and tantalizing advances, abundant mysteries about Alzheimer’s remain. But the millions of people struggling with this heartbreaking disease can take some comfort in the fact that some of the nation’s best minds are determined to solve them.

The Lifestyle Link

Several Alzheimer’s studies at Duke seek to tease out the possible relationship between the disease and lifestyle factors such as diet, supplements, and other medications. Studies from the laboratory of Patrick Sullivan, PhD, in the Duke Aging Center, have shown that diets lower in fat seem to dramatically decrease the risk of developing Alzheimer’s-type brain changes. Population-based studies also reinforce the importance of diet on cognitive health and brain aging.

Welsh-Bohmer leads a large team of investigators with the Cache County Memory Study, a unique long-term research project focused on the population of one fairly isolated Utah county. The study has clearly shown that not everyone who has the APOE4 gene gets Alzheimer’s -- suggesting the importance of other factors in its development. It also seems to confirm the role of diet on cognitive decline in aging and supports earlier studies suggesting that vitamins C and E, anti-inflammatory compounds such as ibuprofen or naproxen (marketed as Aleve®), and aspirin may all help to lower the risk of AD.

“Recent studies show that what’s good for the heart seems to also be good for the brain,” says Doraiswamy. His prescription for a “brain-friendly” lifestyle includes the following tips:

• Manage your “numbers” -- your cholesterol count, blood pressure level, blood glucose level, and weight.
• Take blood pressure, cholesterol, and/or diabetes medications as prescribed. Early evidence suggests that statins and some diabetes drugs may help support mental function.
• Eat a diet rich in leafy and bright-colored vegetables, folic acid, antioxidants, and omega-3 fatty acids. Avoid omega-6 fats like butter and processed oils.
• Complement your diet with B vitamins and folic acid.
• Get aerobic exercise at least two to three times per week.
• Mental exercise is equally vital -- rather than staying entrenched in a routine, “Try new things and do familiar things in novel ways,” Doraiswamy says.
• Maintain social and family relationships -- Doraiswamy calls isolation “a huge risk factor for AD.”
• Manage mental health issues such as anxiety, stress, and depression -- all of these can adversely affect memory.
• Avoid excess alcohol, as it can hamper memory formation.
• Get your memory tested promptly if you are having a problem -- there are many causes that can easily be treated if detected early.

Support to Ease the Burden

"I swore with every fiber of my being that I would never put my husband in a nursing home. I took care of him at home for 12 years. My doctor finally said to me, 'You must put Jack in a nursing home or you'll die, and then we'll put him in a nursing home.' In my heart of hearts, I knew he was right. But now there are nights I can't sleep. I feel I have abandoned him.”

This sad story -- that of the distraught wife of a man with Alzheimer's disease -- is all too common. And it’s the kind of story Lisa Gwyther and her colleagues at the Bryan ADRC and the Duke Family Support Program hear every day. While medicine still seeks effective remedies for Alzheimer’s, support programs can help families cope with the challenges of caring for a loved one who can no longer function and often bears almost no resemblance to the person they knew for decades before the illness struck.

Toward that end, Gwyther and her colleague Edna Ballard have created a family of educational manuals covering every aspect of Alzheimer’s -- from the sexual to the spiritual, from holiday celebrations to financial considerations. With the help of Henry Edmonds, coordinator of the African American Community Outreach Program at the Bryan ADRC, they are working to increase general public awareness of Alzheimer's disease and create a range of support groups and services -- in the process, building a model program now emulated around the nation.

For more information, visit: adrc.mc.duke.edu.