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August 2, 2001

The Search for an Alzheimer’s Cure

http://www.jewishjournal.com/community/article/the_search_for_an_alzheimers_cure_20010803

One in ten people over age 65 have Alzheimer's.  (Billy Ray Stalvey, 70, and his wife, Maxine, at their Myrtle Beach, S.C. home. Maxine was diagnosed with Alzheimer's disease in 1992.)

One in ten people over age 65 have Alzheimer's. (Billy Ray Stalvey, 70, and his wife, Maxine, at their Myrtle Beach, S.C. home. Maxine was diagnosed with Alzheimer's disease in 1992.)

"How do you spell fare?" my father asked.

For a man who had spent a lifetime in business, I was taken aback, but I spelled it for him. He was writing a check for my plane fare to Los Angeles, something he generously undertakes whenever I visit Florida. Today, he looked at his checkbook, then at his register, at the checkbook again, then back at his register in increasing increments of confusion.

Each time I tried to intervene, he grew defensive and angry. By the time he was ready to put pen to paper, he had forgotten what the check was for.

That was two years ago, the last time my father wrote a check. For most people in the beginning stages of Alzheimer's disease, the simplest task, like writing a check, becomes a Herculean undertaking. The brain can no longer process familiar information or function normally. Alzheimer's, a brain-wasting disease, is characterized by the spread of sticky plaques (clusters of dead and dying nerve cells) and tangles (clumps of protein fragments) in the brain. This "brain debris" causes delicate nerve cells to atrophy, which in turn prevents the production of neurotransmitters essential for firing up memory and reasoning.

As the disease progresses, an afflicted person will eventually lose more cognitive functions and display decreased physical ability, as well as personality and behavior changes. Communication becomes strained as the person struggles to remember words and thoughts; it is not uncommon for people with Alzheimer's to withdraw from society altogether, finding themselves unable to communicate, remember or reason.

That's what happened to my father. Once an outgoing man who played golf every morning of his retired life and bridge every afternoon, he slowly lost his confidence to communicate as his short-term memory deteriorated.

Eventually he stopped playing bridge (in actuality, the men threw him out of the game), but he had already withdrawn, unable to remember the easiest hand. This was a huge blow to my mother, who found herself, for the first time in her married life, the one to take charge. Today my father is totally dependent on her care.

Alzheimer's disease is the most common cause of dementia. According to the Alzheimer's Association, one in 10 persons over the age of 65, and nearly half of those over 85, have the disease. Today, 4 million Americans have Alzheimer's. Unless a cure or prevention is found, that number will jump to 14 million by the middle of the century. In a national survey, 19 million Americans said they have a family member with Alzheimer's; 37 million know someone who has it. In most cases, a person lives an average of eight years -- but up to 20 -- after the initial diagnosis.

This disease isn't cheap. U.S. society spends over $100 billion a year on Alzheimer's disease. Neither Medicare nor private health insurance covers the long-term care most patients require. According to the Alzheimer's Association, seven of 10 people with the disease live at home, with 75 percent of the care provided by family and friends. The remainder is covered by paid care, costing an average of $12,500 per year. Families pay almost all of that out of pocket.

Nursing homes report that half of their residents have the disease, where the average care runs to $42,000 a year. On the Alzheimer's Association's Web site, a 1998 study concludes the average lifetime cost per patient is $174,000.

In Los Angeles, the costs can soar. At the Jewish Home for the Aging in Reseda, the daily cost per person in the Alzheimer's dementia unit, a skilled nursing facility, is between $175 to $189 per day. The facility is a secured unit with a small ratio of nurses to patients, and offers daily activities for all levels of the disease; for example, adult education for those who are still relatively high functioning, exercise classes for those still fit.

By next year, the Jewish Home for the Aging will open an entire building dedicated to Alzheimer's disease. Because a person can have Alzheimer's and maintain good health, the home does not say what the average lifetime cost per person can be, only that it varies widely: some patients may enter the home in the late stages, others may get the disease in their early 70's and live to be 100.

Recently, there has been a spate of new research. The two best-known studies have shown great promise for understanding the disease. The Nun Study by University of Kentucky epidemiologist David Snowdon, who recently published "Aging with Grace" (Bantam), looks at nearly 700 nuns, studying lifestyle and environment, to determine a variety of factors that contribute toward the disease. Another is the just completed clinical trial using Nerve Growth Factor (NGF), conducted by UC San Diego (UCSD), in which doctors surgically implanted genetically modified tissue into the brain of a 60-year-old woman at the beginning stages of Alzheimer's.

Both studies leave scientists and doctors optimistic, yet reluctant to conclude that they are any closer to finding a cure.

The Nun Study, conducted over a 15-year period by Snowdon, studied nuns from the order of the School Sisters of Notre Dame, researching their personal and medical histories, testing for cognitive function, and even dissecting their brains after death. Forty-five percent of the nuns, who are now between the ages of 85 and 106, have fallen prey to the disease.

Scientists know that genes play an important role in Alzheimer's, but Snowdon chose to focus on environmental and lifestyle factors. He found that an active intellectual life; a college education; a flare for words and a good diet all contributed to prolonging a sharp mind. In one study, he found that the nuns who used complex ideas and positive emotions (in written autobiographies that they submitted upon entering the convent) were the ones with the clearest mental faculties, over the longest period of time. He also researched a finding by a British team that found a low level of folate (a nutrient) in the blood of Alzheimer's patients. After analyzing dissected brains, Snowdon concluded that folate, or folic acid, helped to counteract the effects of Alzheimer's-type damage to the brain.

But Snowdon is adamant that not one factor alone causes or saves one from the disease. "Blood circulation, medications, nutrition, genetics -- there are many links that factor into dementia," Snowdon noted on NPR's "Science Friday" on July 6.

The UCSD clinical trial using NGF, led by UCSD neurologist Mark H. Tuszynski and neurosurgeon Hoi Sang U, is more elusive because it is the first-time gene therapy has been used on a human to treat a disease of the nervous system. According to Tuszynski, director of UCSD's Center for Neural Repair, it will be months before any results are determined, but to date, "there have been no major adverse events."

In previous studies, NGF has been shown to be effective in reversing the signs of aging in primate brains. In a study in 1999, the atrophied brain cells of aging monkeys were returned to nearly normal size and quantity following the surgical implant of cells genetically altered by NGF.

In the UCSD procedure, NGF was inserted into a sample of the patient's skin cells. Over the next few months, the modified cells produced a high quantity of NGF, which was then implanted into the patient's brain. The procedure targeted an area of the brain important for memory and cognitive function.

"NGF gene therapy is not expected to cure Alzheimer's disease, but we hope that it might protect and even restore certain brain cells and alleviate some symptoms, such as short-term memory loss, for a period that could last a few years," Tuszynski said.

The current patient clinical trial is taking place through UCSD Alzheimer's Disease Research Center (ADRC), one of five centers supported by the National Institute of Aging of the National Institutes of Health. Currently there are 30 ADRCs in the country.

Dr. Leon Thal, head of UCSD's department of neurosciences, which oversees the clinical trials, believes, like others in the field, that it is important to make an early diagnosis concerning Alzheimer's. "There are medications to treat Alzheimer's symptoms -- four [cholinesterase inhibitors] are now FDA-approved." Also every patient "has the right to know what disease he has," Thal said.

Some patients, however, may not want to know. With clinical trials still in the experimental stage, and any effective medications to prevent Alzheimer's years away, finding out might be considered a death sentence. But with research spanning the globe, and technological breakthroughs on the horizon, doctors and scientists are sounding more hopeful.

Neurologist Rudolph Tanzi, author of "Decoding Darkness: The Search for the Genetic Causes of Alzheimer's Disease," speaking on "Science Friday," said that in the next five to 10 years, new medications will halt Alzheimer's-type damage to the brain before symptoms hit.

"Prevention is the name of the game," he said. These medications, he pointed out, are similar to the protease inhibitors used by AIDS patients, and will target those genetically predisposed to Alzheimer's disease.

Snowdon, who recently received funding to publicly endow the Nun Study, has stated that there is strong evidence that the tangles and plaques found in Alzheimer's patients starts decades earlier -- another reason to focus on preventive measures to stop the damage to the brain. For now, Snowdon feels confident enough to suggest a few easy lifestyle measures, to stave off memory decline: intellectual activities to stimulate the brain, avoiding head injury and strokes (low-cholesterol diet), eating fruits and vegetables, and using a multivitamin and folic acid supplement.

"This is a family disease," Snowdon concluded. "It touches everyone."


The following organizations can be contacted for more information about Alzheimer's disease.



Alzheimer's Association is a nonprofit group that supports patients, families and researchers: www.alz.org.

Alzheimer's Disease Education and Referral Center is a National Institute on Aging service that provides information on the disease and links to a clinical trials database: www.alzheimers.org.

Eldercare Locator is a government-sponsored service that provides information on resources for older persons: (800) 677-1116.

American Academy of Neurology is a professional association providing information on new clinical practice guidelines for Alzheimer's: www.aan.com.

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