UW researchers try to find the secret to treating Alzheimer’s disease
Helen Knudson Pulsifer, ’50, was a person who was “clearly in charge.” She had to be. As executive director of the King County Bar Association, she kept track of about 4,100 members, running a staff of 25 with a budget of about $1.5 million.
During the 1980s, she worked with everyone from Federal Judge William Dwyer, ’51, to William H. Gates Sr., ’49, ’50. “Helen was always dealing with the board of trustees and a set of officers who were very busy, very prominent attorneys in town. She had lots of energy, lots of creativity and lots of demands on her time,” says attorney Linda Strout, ’69, who worked closely with Pulsifer in the bar association’s young lawyers division.
But near the end of that decade, family and co-workers started noticing a change in Pulsifer. She was due at someone’s house for dinner, and she’d forget to show up. “When she was 60 or so, she started getting ‘drifty,’ ” says daughter Lindsay Pulsifer, ’07.
Gradually, it got to the point where Pulsifer was driving and she’d get lost, sometimes cruising around the city until she figured out where she was. She would become embarrassed when it dawned on her that she didn’t know where she was going.
The Alzheimer’s Foundation of America estimates that 5 million Americans currently have Alzheimer’s disease. By 2050, that number may reach 16 million, an epidemic of suffering.
Pulsifer either repeatedly lost her credit cards or used them to order useless items from a catalog. Sometimes she would order two of the same item, forgetting she had already purchased one. “It became this family joke,” says Lindsay. “Someone would get a salsa maker two years in a row. We couldn’t figure out what she was thinking, but then to get two of them?” The final straw was when Pulsifer ordered around $1,800 worth of merchandise in one day.
Pulsifer’s children—Lindsay, Luke, Dave and Janet—had helped with her health care for years and watched her overcome a bout with colon cancer. In 2000, doctors diagnosed mild dementia. Two years later, they said her “drifty” behavior was now Alzheimer’s disease. “She’s a person who was used to being mentally agile and able to consider complex topics,” says Lindsay. “It compounds the tragedy when she recognizes she’s not able to think that way.”
The Alzheimer’s Foundation of America estimates that 5 million Americans currently have Alzheimer’s disease. By 2050, that number may reach 16 million, an epidemic of suffering.
A brain disorder first identified in 1906, Alzheimer’s is the most common form of dementia, a general term for the loss of memory and other intellectual abilities. The condition causes problems with memory, thinking and behavior, and it is not a normal part of aging.
The destruction and death of nerve cells in the brain cause memory failure, personality changes and other symptoms. Plaques, or deposits of a protein fragment called beta-amyloid, build up in the spaces between nerve cells. Tangles, or twisted fibers of another protein called tau, accumulate inside cells.
The plaques and tangles first form in areas that control memory. They gradually spread to other areas, eventually affecting most of the brain. Autopsies show that most people develop some plaques and tangles as they age, but those with Alzheimer’s tend to develop far more. Scientists do not yet know exactly what role plaques and tangles play, but most believe that they block communication among nerve cells, disrupting processes the cells need to survive.
Alzheimer’s can cause dramatic personality changes, as seen in the award-winning performance of Julie Christie in the recently released film Away From Her. High profile cases include former President Ronald Reagan, novelist Iris Murdoch, boxer Floyd Patterson and actor Charlton Heston.
Lindsay Pulsifer, ’07, (left) comforts her mother, Helen.
Pulsifer’s family was fortunate. Their mother managed to live alone until two years ago, when they moved her into assisted living. But her Alzheimer’s has progressed to the point where she recently forgot her 80th birthday, despite repeated calls from her children to remind her of plans for a catered lunch.
For many years Alzheimer’s disease seemed like a death warrant with no hope for a reprieve. But now research at the University of Washington, other universities and health-care organizations is beginning to offer hope for those stricken with this form of dementia—and their families. Two UW drug-related studies show some promise, and a local patient registry—the only one of its kind in the world—is offering tantalizing hints at the cause of this disease.
In a study published last August in Neurology (and subsequently covered in the New York Times), UW researchers found that elderly people who had taken statins, or cholesterol-lowering drugs, had a lower frequency of tangles in their brains.
Psychiatry and Behavioral Sciences Professor Gail Li was looking at risk factors for Alzheimer’s. “Around the year 2000, there was a notion that elevated cholesterol increases the risk of Alzheimer’s disease,” she says. At the same time, there were epidemiological studies that showed statins might help prevent Alzheimer’s.
Li’s study was the first to compare the brains of people who had taken statins to those who had not. Researchers autopsied the brains of 110 deceased members of Group Health Cooperative, aged 65 to 79, who had donated their bodies for scientific research.
The study was observational—research subjects did not intentionally take certain medications, nor was there a control group—so the results are not scientifically proven, but they were encouraging. The statin users had a lower frequency of the tangles in their brains.
Gail Li observed that elderly people who had taken statins, or cholesterol-lowering drugs, had a lower frequency of “tangles” in their brains.
“People tend to jump [to the conclusion] that statins can prevent Alzheimer’s and we really can’t say this,” Li says. A lot more work needs to be done. Previous studies in the U.K., for example, found no difference in statin versus non-statin users on rates of dementia.
But Li’s study is significant, says Eric Larson, ’77, executive director of Group Health’s Center for Health Studies and a former medical director at UW Medical Center. “This suggests that if you treat the vascular risk a person has with a drug like a statin, it may reduce the risk for changes seen with Alzheimer’s,” says Larson, who has studied dementia since the late 1970s.
In another UW study, Professor Thomas Montine, director of neuropathology at Harborview Medical Center, is looking at antioxidants as they relate to Alzheimer’s. Past research by Montine and colleagues at the University of Kentucky has shown that oxidative damage occurs in the brains of those with Alzheimer’s, particularly in the middle and late stages of the disease. This damage also eventually kills brain cells.
Montine is measuring free radical damage in the different components that make up the brain. “It remains a legitimate question—does supplementation with antioxidants (either through pills or diet) have any beneficial effect?” he asks.
Montine says his research—looking at brains of people who have donated their organs for science—builds on that of UW colleague Shelly Gray in the Department of Pharmacy. Gray’s research indexes patients’ exposure to common antioxidants including vitamins E and C, and other components of multi-vitamins. Her latest findings, published last month (February 2008) in the Journal of the American Geriatrics Society, found Vitamin E and C do not reduce risk of dementia or Alzheimer’s. Montine’s studies use that data and look at the biochemical exposure in the brain. Results from his antioxidant work will be published soon, he says.
Li, Montine, Gray, Larson and other Alzheimer’s researchers depend on two local patient registries to support their work. One is a database of patients with dementia that covered a 10-year period and includes those willing to have autopsies performed after their death. The other is an on-going database that enrolls cognitively healthy patients and follows the subjects forward in time, with researchers looking for signs of dementia.
Both registries are based at Group Health, which has detailed health records going back to the time its members first enrolled in the health coop. The Group Health-based information—used by UW and other researchers in the Puget Sound area as well as across the country—is unique, says Larson. “To my knowledge, this is the only place in the world where you can link detailed drug exposure data [to dementia],” he says.
“There’s no pill that works even though people are looking for one.”
Eric Larson, ’77, executive director of Group Health’s Center for Health Studies
While not a part of these registers, Helen Pulsifer has participated in Alzheimer’s studies, including one by Psychiatry and Behavioral Sciences Professor Soo Borson, director of the UW’s Memory Disorders Clinic.
Borson is a leader in screening for Alzheimer’s and treating patients. In a study published last April in the Journal of General Internal Medicine, Borson and UW colleagues concluded that dementia screening by office staff (including medical assistants) is feasible in the primary care setting. But doctors are only likely to take action (diagnose dementia, refer the patient to a specialist or prescribe medications) if the cognitive impairment—or signs of dementia—is severe.
But there is a problem with developing better screening tools—do patients and their families really want to know the bad news? Some groups—including the newly formed Alzheimer’s Disease Screening Discussion Group—are pushing for routine screening of older people for the disease, while others caution about potential negative consequences.
Borson says if providers make a diagnosis of some dementia, they are not sure what they can do with the information. “Doctors don’t do much with the [screening] data, and that is where our work is moving now,” she says.
Five prescription drugs are currently approved by the U.S. Food and Drug Administration to treat people with Alzheimer’s: Razadyne, Exelon, Aricept, Cognex and Namenda. The first four medications may help delay or prevent symptoms from becoming worse for a limited time and may help control some behavioral symptoms. Namenda has been shown in some studies to allow patients to maintain certain daily functions a little longer.
Borson, who has worked with Alzheimer’s patients for some 20 years, says the disease is becoming more high profile. Pharmaceutical company interest is piqued, too, in light of the statin and other drug-related studies. With predictions that show a 70 to 100 percent increase in Alzheimer’s cases in the next 20 years, there is a small “arms race” to work on screening, better care delivery, possible prevention methods and, of course, discovering drugs that can hold back dementia.
Larson said all these factors create a “stay tuned” environment. “There’s no pill that works even though people are looking for one,” he says. “With genetic work that’s going on, it may be possible some day to define people who are never going to get the disease and people at high risk for whom a more aggressive prevention strategy, including perhaps even a pill, might be indicated. We’re not there yet.”
Lindsay Pulsifer recognizes that we’re not there yet, though she remains hopeful that UW and other research may make things different for future generations.
Given the family history, Lindsay, 55, also says she can’t help but think about her own health issues. “I used to be 100 percent reliable in a hallway conversation,” she says. “I would never forget to follow up, but I have totally lost that ability and I know it. Frankly, it has me fairly scared.”
Reducing the risk
While there’s no sure fire way to prevent Alzheimer’s disease, Eric Larson, ’77, executive director of Group Health’s Center for Health Studies and a former medical director at UW Medical Center, says reducing your risk of heart disease could help. His tips include:
- Exercise regularly, stay physically fit
- Watch your diet to control weight
- Treat high blood pressure (if you have it)
- Stay socially engaged
- Pursue mentally-stimulating activities
- Stay tuned (for more research findings)
Warning signs or normal memory lapses?
Alzheimer’s symptoms:
- Forgets whole experiences
- Rarely remembers later
- Gradually unable to follow directions
- Gradually unable to use notes
- Gradually unable to care for self
Normal age-related memory changes:
- Forgets part of an experience
- Often remembers later
- Usually able to follow written/spoken directions
- Usually able to use notes
- Usually able to care for self