Researchers hope for breakthrough on Alzheimer's

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NEW YORK: ‘‘I've lost myself,” a patient named Auguste Deter told German psychiatrist Alois Alzheimer in the early 1900s.

Her case became the foundation of Alzheimer's work on a disease that was named after him and that, more than a century later, has become an uncontrolled and little understood epidemic.

Millions of Americans, including about 7,000 Sonoma County residents, will follow Deter's descent into dementia in the coming decades unless medical research finds a cure or effective treatment for Alzheimer's disease.

As the leading edge of the baby boomer generation turns 65 this year, the so-called “silver tsunami” confronts a disease that robs people of memories — in effect their identity - and exacts an appalling cost on their loved ones and society as a whole.

There are now 5.3 million Americans living with Alzheimer's, and the cost of their care, including treatment, prescription drugs, nursing home bills and lost wages, exceeds $170 billion a year.

By 2050, the caseload will swell to 13 million Alzheimer's patients, and the cost, with inflation, could reach $500 billion. In California, the number of people with Alzheimer's is expected to nearly double from 588,208 today to more than 1.1 million by 2030.

Sonoma County's Alzheimer's population of 8,902 in 2008 is set to reach 15,799 in 2030, a 77 percent increase.

At a research center on a Novato hilltop, neurobiologist Dale Bredesen hopes to forestall that scenario with a breakthrough on Alzheimer's, possibly in as little as five years.

“We have a couple of interesting candidates,” said Bredesen, professor and founding president of the Buck Institute for Research on Aging, housed in a sleek structure west of Highway 101 at Novato.

He's talking about the results of two years of lab work spent testing thousands of compounds on brain cells and laboratory mice that have been genetically modified to develop Alzheimer's disease. Bredesen won't name the two compounds, but in three years he hopes to begin testing them on humans.

The lab rodents have shown improvement, but as Bredesen said during an interview in his office, “Until you can do it in a human, you haven't done anything.”

The stakes are high. Of the seven leading causes of death in California, only two - Alzheimer's and diabetes, the epidemic tied to obesity - are increasing dramatically.

Deaths due to pneumonia, stroke, heart disease and respiratory disease all declined between 2000 and 2004, according to the state Department of Public Health. Cancer deaths were up a little over 1 percent.

Diabetes deaths were up nearly 15 percent, while Alzheimer's deaths, although lower in number than the other six diseases, were up 58 percent over the five years.

Sonoma County averaged 150 Alzheimer's deaths a year from 2003 to 2005, with an age-adjusted rate of 27.5 per 100,000 population, the 10th highest rate among the 58 counties, according to state figures. Napa County's rate of 39.1 per 100,000 population was second highest in California.

Statewide, the age-adjusted death rate for Alzheimer's was 22.1 per 100,000 population.

Mental degeneration due to Alzheimer's does not directly kill people, but its effects lead to fatal complications, such as pneumonia, infection and blood clots, Bredesen said.

People experience memory loss in the early stages of the disease, reflected by Deter's lament to Dr. Alzheimer. But as memory and sense of self slip away, patients lose their insight into the disease's effects, Bredesen said.

The heart, lungs and other organs continue to function, and the senses of taste, touch, hearing and vision remain. Patients tend to be “very likeable, and may seem to be carefree,” he said.

For families, the impact of watching a loved one erode mentally is devastating. Compounding the emotional strain, relatives, primarily spouses or adult children of the patient, become the caregivers and are often forced to either miss work or give up their jobs.

California caregivers provide 952 million hours of unpaid care per year with an economic value of more than $10 billion, according to a state report on Alzheimer's.

Caring for people with severe memory loss involves multiple impacts: financial hardship, health problems, emotional stress such as depression or anxiety, and sleep disturbance, the report said.

Baby boomers are now well within Alzheimer's range, which typically begins in the 50s. At age 65, about one in 20 people are affected, and the prevalence of Alzheimer's increases up to age 85, when about half of people have the disease. Those who remain unaffected at 90 seem to be relatively immune, Bredesen said.

In the face of the Alzheimer's onslaught, medical science so far has little to offer. A handful of measures, including exercise and nutritional supplements, can forestall the symptoms about five years.

Two medications - Aricept (donepezil) and Namenda (memantine)- have a limited effect, which Bredesen, a physician who has spent 18 years in Alzheimer's research, describes as “better than nothing, but just barely.”

Bredesen's first scientific paper on Alzheimer's, published in 1993, made a front page story in USA Today.

Clinical trials of prospective Alzheimer's remedies on people have resulted in “almost universal failure,” Bredesen said, leading to his conclusion that “our fundamental understanding of the disease is lacking.”

Two years ago, Bredesen's lab at the Buck Institute began working under a new premise, called the “imbalance theory.” It examines a tilt between the four horsemen of memory loss and what he calls the “whollycq trinity” of memory retention.

The theory posits that there are four types of molecules in the brain responsible for forgetting, or breaking the connections between brain cells. And there are three types of molecules that promote maintenance of those connections, retaining memory.

Alzheimer's disease upsets the balance between the horsemen and the trinity molecules, leading to memory loss. Bredesen is now all in, as a poker player would say, on the premise that his theory will lead to a breakthrough. He said he and his research group are currently the only Alzheimer's research laboratory making that bet.

“We can make the disease much better in mice,” he said. But ultimately only human trials of the prospective remedies matter, and he hopes to start those within three years. The trials would run 18 months to two years, establishing a five-year time frame for his theory to succeed or fail, at least initially.

With many other labs also working on Alzheimer's, Bredesen, a member of the government's National Advisory Council on Aging, said he expects a development in the next five to 10 years.

"We hope our new insight will lead to a s is going to be the big breakthrough in treatment," he said, "but from wherever it comes, any significant treatment for this disease would be welcome relief for millions."