~ 091511 Scientists Work to Understand, Treat and Find a Cure for Alzheimer's

~ 091511 Scientists Work to Understand, Treat and Find a Cure for Alzheimer's
Howard Cohen, The Miami Herald

Louise Dagher watched her husband of 49 years, a man fluent in six languages and a top economic executive with BP, painfully slip away from the family because of Alzheimer's disease.

"Terrible. It changes your life completely," said Dagher, 77, whose husband died in 2008. "I lost all my friends. They would phone, but I would never return the calls because I was so busy taking care of Joe. I was watching Joe all the time, and he was sick for nine years."

Joyce Pinn Fox can relate. A half-century ago, the Aventura resident watched her mother decline and die from complications from Alzheimer's disease, the most common form of dementia.

There is no cure for Alzheimer's, but researchers, many of whom launch clinical trials in South Florida, are optimistic as the genetics, the pathology and the intricacies of Alzheimer's become better known. An estimated 450,000 Floridians have Alzheimer's disease, a number that is expected to grow by another 135,000 or so by 2025, according to the Alzheimer's Association, a national group that focuses on Alzheimer's research. Florida ranks second only to California in Alzheimer's patients.

"We want to map the genetic landscape of Alzheimer's so we can understand the landscape," said Dr. Margaret Pericak-Vance, director of the John P. Hussman Institute for Human Genomics at the University of Miami Miller School of Medicine and recipient of this year's lifetime achievement award by the Alzheimer's Association.

"The next step would be trying to understand why certain people have certain genes contributing and maybe environmental targets. We are trying to understand what causes Alzheimer's so we can develop the next line of therapies."

For its victims and their families, it's personal.

"My mom ended up in a crib for nine years," Fox said. Her father, a dentist, put his practice on hold to help care for her and wound up broke. "It was really hard as a family to watch this. Changed my whole life. She was 80 when she died but was a vegetable for nine years."

Now 80 herself, Fox has been diagnosed with mild cognitive impairment (MCI) -- very early Alzheimer's -- by Dr. Ranjan Duara, medical director of the Wien Center for Alzheimer's Disease and Memory Disorder at Mount Sinai Medical Center in Miami Beach.

Fox recently participated in a clinical study at Wien. That study -- the MCI Cognitive Stimulation/Physical Exercise Study (Cogex) -- looked at whether physical activity could improve cognitive function. She is about to enter a new medication trial at the center, where researchers are searching for a vaccine against amyloid protein buildup in the brain, one of the factors thought to contribute to the disease's progress.

Fox, a 2010 Breaking the Glass Ceiling Award honoree by the Jewish Museum of Florida, had been executive director of global credit for American Express, where she managed portfolios representing 43 countries and $50 million in lending. She is a member of Phi Beta Kappa, the nation's oldest academic honor society.

But when she began falling a few years ago, as her mother had many decades ago, and her organizational skills weren't as sharp, she went to the Wien Center and volunteered for the clinical trial.

"Unless you've seen someone suffer with that disease, you can't understand," she said from her Aventura home. "If I can help, I would be very happy to do anything."

Healthy heart, healthy brain

In July, at the Alzheimer's Association International Conference in Paris, which gathered 5,000 scientists from around the world, including Pericak-Vance, scientists reported that falls are more common among individuals with the earliest brain-changing impact of Alzheimer's.

A brain scan, to look for deposits of a protein called beta amyloid, found that individuals who had fallen had more of these deposits on the brain than those who hadn't. It is believed that a build-up of the plaque in the brains of people with Alzheimer's occurs prior to cognitive decline.

"Amyloid is a protein used actively by the brain and seems to have some physiological function and metabolizes very quickly ... but when it sticks around, it has multiple effects, which include initiating an inflammation in the brain," Duara said. The build-up affects the synapses between nerve cells and blocks synaptic activity in the very early stage.

"The hypothesis is amyloid initiates the disease process," said Duara, who is a neurology professor at UM and Florida International University. "By the time a person manifests the disease, it's probably too late to start treating them. Amyloid by itself doesn't govern what happens to them subsequently, but it starts the ball rolling."

Knowing this, doctors are working to diagnose the disease earlier.

"Now that we understand how these things form, we can try and attack these very things," said Dr. Bruno Giordani, the director of the neuropsychology section at the University of Michigan and one of the scientists who attended the Paris conference. "Everyone is interested in looking at this early, even though there are no medications yet that clearly are affecting or modifying this disease."

Still, there is plenty that the public can do that may stall or delay the onset of Alzheimer's, Giordani said, citing controlling hypertension, diabetes, obesity and other heart-related ailments.

Physical exercise -- such as walking, running or swimming -- has shown positive results in potentially delaying Alzheimer's and other memory disorders by increasing blood flow to the brain. The brain needs 25 percent of your body's supply of oxygen to function properly. Blood flow brings oxygen and other nutrients to the brain. When the brain doesn't get these nutrients because your carotid arteries -- which supply oxygen to the brain -- are blocked, brain tissue deteriorates, leading to a decline in function.

A recent study at Texas Health Presbyterian Hospital in Dallas found that women ages 60 and older who walked briskly for 30 to 50 minutes a day, three to four times a week for three months, had boosted their blood flow to the brain by as much as 15 percent.

"If you have a healthy heart, that's very important for a healthy brain," Giordani said.

Doctors now also know that changes in gait and balance may appear as early indicators of Alzheimer's, even before noticeable memory changes.

"I have forgetfulness, but I'm much better now than when I started four months ago. We've got to find a cure somehow," said Fox, who still volunteers as an usher at performing-arts theaters in Aventura, downtown Miami and Coral Gables.

"It's often said that Alzheimer's has multiple victims -- the patient is only one of them," Duara said. "The family is affected in many different ways. It affects the ability to work. There is a much higher incidence of depression -- especially in immediate caregivers -- and higher incidents of medical illnesses like cancer and heart attacks in the caregivers of patients with Alzheimer's."

Early detection is key to intervention

Alzheimer's, the sixth-leading cause of death in the United States and the fifth for those age 65 and older, grew by 66 percent in the number of deaths between 2000 and 2008. By contrast, breast and prostate cancer, heart disease, stroke and HIV all posted declines ranging from 3 percent to 29 percent.

There are 5.4 million Americans with Alzheimer's and more than 35 million worldwide. By 2050, the association estimates that 16 million Americans will have the disease. Nearly half of people age 85 and older now have Alzheimer's.

In 2011, the cost of caring for people with Alzheimer's will total $183 billion, an $11 billion increase over last year. By 2050, the Alzheimer's Association puts that cost at $1.1 trillion unless a cure is found.

The disease has a public face, too. Over the past 10 years, Alzheimer's has led to the deaths of former President Ronald Reagan and actor Charlton Heston. In May, pop singer Glen Campbell, 75, garnered renewed media attention when he announced that he had the disease, and in late August released his final studio album Ghost on the Canvas. Just last month, Pat Summitt, the University of Tennessee's women's basketball coach, who has won more games than any other college coach -- men's or women's -- was diagnosed with early-onset Alzheimer's.

One of the goals in Alzheimer's research is to prevent the destruction of brain cells by intervening early in the disease.

"In the past five years, we've made tremendous progress in understanding the path of the physiology of the disease," said Dr. David Loewenstein, a clinical neuropsychologist at the University of Miami. "Now, for the first time, we have been able to look at the accumulation of beta amyloid in the brain ... 10 to 15 years before clinical symptoms manifest themselves. If we can use these early-detection techniques to find people at risk, we are much better able to develop agents to prevent the disease or slow the disease down before it destroys brain tissue."

At the Paris conference, researchers discussed a Phase II study of the new drug, Pfizer's Bapineuzumab, and its use for mild to moderate Alzheimer's. The drug, one of five used for Alzheimer's, was well tolerated. "There was go-ahead to do more research on that drug," Giordani said. "So far, none of the drugs actually modify or stop Alzheimer's, but Bapineuzumab is one of the newer generation of drugs. This is where research is going -- on these drugs that try to modify the disease and interfere with the development."

Researchers also presented findings from the Dominantly Inherited Alzheimer's Network (DIAN) study, which was funded by the U.S. National Institute on Aging. DIAN is looking at young-onset familial Alzheimer's caused by rare genetic mutations. The initial enrollees included 150 individuals who, it was determined, were destined to get the disease because of their genes. Biomarkers from this group suggested that brain chemistry and imaging changes can be detected at least 10, and maybe 20 years, before the onset of Alzheimer's.

Researchers also have found, in a preliminary study, that the width of certain blood vessels in the back of the eye could serve as biomarkers since they were significantly different for people with Alzheimer's.

"Right now, imaging of the brain that looks at its functionality, to see if there are some suggestive markers that this person has Alzheimer's disease, is where a lot of the research is," said Dr. Elizabeth Crocco, the medical director of the University of Miami's Memory Disorder Clinic.

"The other thing we're working on, and though not ready for prime time, is genetics. Peggy [Pericak-Vance] has been the leader in uncovering the genetic clues that can increase the risk of Alzheimer's," said Dr. Ralph Sacco, chairman of neurology at the University of Miami and executive director of the Evelyn F. McKnight Brain Institute. "There may be genetic factors we need to discover that would open up new angles for understanding and hopefully treating white-matter disease."

Future reasons for optimism

Though there's much work to do -- the disorder, though identified more than 100 years ago, didn't see serious research until the 1970s and 1980s -- experts are optimistic about recent developments.

"One of the things that holds us back is, if we had all the money in the world, things would be moving a lot faster because the technology is there," said Pericak-Vance. "The University of Miami is involved in international collaborations that will help us find a treatment for these patients. If we could move more money into research, it would be amazing."

Duara agreed. "I'm quite optimistic we'll see a cure," he said. "My projection is in the next five years or so we'll find something -- a cure is too strong a word -- but certainly a treatment that is effective in slowing down the progression, resulting in some improvement. One thing we learned about the brain, even in older age, is it has an amazing capacity to regenerate.'


(c)2011 The Miami Herald

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