Alzheimer’s study at Mount Sinai in Miami Beach focuses on possible prevention

For years now, Graciela Fowler has watched as her elderly relatives have succumbed to Alzheimer’s, an irreversible brain disease that destroys memory and thinking skills. At 66, she worries about succumbing to a similar fate.

“It’s heartbreaking when you see people who were so bright and independent go downhill,’’ says Fowler, a retired social worker. “It’s very sad.’’

That’s why Fowler has decided to volunteer for what may be a groundbreaking research trial at Mount Sinai Medical Center in Miami Beach with Dr. Ranjan Duara, the medical director of its Wien Center for Alzheimer’s Disease and Memory Disorders. Mount Sinai, the only site in South Florida participating in the study, is actively recruiting volunteers between ages 65 and 85 for the trial. Duara figures the center will have to screen about 200 to get the actual 30 patients needed.

The Anti-Amyloid Treatment in Asymptomatic Alzheimers’s study — known as A4 — is looking at cognitively normal elderly individuals, not those with signs of memory loss or disorder. It will test them for amyloid plaques in the brain. Those who test negative for these plaques will continue in the study as a control group. Those who test positive will be assigned at random to receive a placebo or a once-a-month infusion of an antibody that targets amyloid and rids the brain of these plaques, a hallmark of Alzheimer’s brains.

Duara said the study hopes to determine whether decreasing amyloid with antibody treatment can slow the memory loss associated with amyloid buildup. “The actual outcome we will be looking at is the slope of change,” Duara explains. “Is the slope steeper than those not treated or those without amyloid?’’

The A4 study, a large public-private partnership funded by the National Institute on Aging, drugmaker Eli Lilly and several philanthropic organizations, is enrolling participants — it hopes to recruit 1,000 seniors — at more than 60 sites throughout the United States, Canada and Australia this spring. There are three other Florida sites: the Mayo Clinic in Jacksonville, the University of South Florida’s Health Byrd Alzheimer Institute and the Premiere Research Institute in West Palm Beach.

The Wien Center is particularly interested in recruiting older Hispanics for the study, a demographic group that is usually underrepresented in clinical trials.

An added advantage to the study: “We are also testing the hypothesis that amyloid plaques cause the deterioration in skills,’’ Duara adds. Right now experts don’t know whether the plaques are the cause or the byproduct of the disease.

Amyloid plaques, along with tangled bundles of fibers called neurofibrillary tangles, are two of the main features of Alzheimer’s, which affects more than 5 million Americans. Another feature is the loss of connections between neurons, or nerve cells in the brain. These are considered the main suspects in the cause of brain-cell death in people suffering from Alzheimer’s.

Despite the prevalence of Alzheimer’s — it’s the sixth leading cause of death in the country and the number of people affected by it is expected to triple by 2050 — there is yet no cure or way to prevent it. This makes studies such as the A4 and others conducted by local researchers that much more urgent.

Theories abound about why a brain affected by Alzheimer’s has many fewer cells and many fewer connections among surviving cells than does a healthy brain. At the University of Miami’s Miller School of Medicine, Barry Baumel, a professor in the department of neurology, is focusing on neurons, the nerve cells that carry information from one cell to another, and on neuro-protectors. Alzheimer’s disrupts the process of cell communication by killing neurons and damaging the brain’s communication network. Baumel’s research looks at various drugs that can serve as neuro-protectors to prevent the disease or slow its progression.

It may be that “a multiplicity of abnormalities cause Alzheimer’s,’’ Baumel says, adding that research on the disease is headed in many different directions. There is a school of thought that draws a strong connection between Alzheimer’s and heart and vascular health. Some autopsy studies have shown that as many as 80 percent of individuals with AD also have cardiovascular disease.

“You can have plaques and tangles and not develop the symptoms of Alzheimer’s,’’ Baumel points outs. “So does this mean you have to have a critical mass (of plaques)? Does the brain have to show vascular disease?’’

Experts also are researching the genetic components of Alzheimer’s. Dr. Margaret Pericak-Vance, director of the Hussman Institute for Human Genomics at UM medical school, is known for discovering the APOE4 susceptibility gene for Alzheimer’s. Among her current research projects: She’s trying to find other Alzheimer’s-linked genes in hopes of developing new drugs to target them.

Despite the numerous studies, Alzheimer’s continues to intrigue — and stump — researchers. Which is why Graciela Fowler is anxious to make herself available for the Mount Sinai research. “I do it for myself but I also do it for science,’’ she says.

In the meantime, medical experts point to emerging evidence that suggests you can take steps to keep your brain healthy as you age:

• Stay physically active. Exercise keeps good blood flow to the brain and helps promote new brain cells.

• Adopt a healthy diet. Cholesterol may contribute to brain cell damage, but a diet rich in vegetables and fruit may help protect your brain.

•  Stay socially and mentally active. This strengthens connections between nerve cells and may even create new nerve cells.