Study of early Alzheimer's patients may provide clues for prevention
Mark Stelzer first noticed the problem when he had to do spreadsheets for his job at Boeing. He seemed increasingly dependent on pen and paper to follow directions.
"They couldn't figure out why he couldn't remember more than one or two instructions at a time," remembered his wife Judy Stelzer. "It got to the point where he was writing everything down and he was doing nothing but (documenting) what he was doing on each step."
Stelzer, 66, didn't know why his performance was declining.
"I just wasn't getting my work done," he said. "I had a very technical job, and I was doing very well prior to that. It was just very frustrating."
When Stelzer started having trouble following ordinary dinner table conversation, the family knew it was time to see a doctor.
Mark Stelzer had become one of the estimated 5.4 million Americans suffering from Alzheimer's disease. The terminal affliction of the brain slowly robs its victims of their memory.
This week Washington University researchers are reporting results at an international conference in Paris that could allow some patients to be diagnosed years, perhaps as much as two decades, before the disease shows symptoms.
Washington University is one of 10 sites worldwide studying a total of 192 patients suffering from a rare early onset version of the disease. Earlier findings from the Dominantly Inherited Alzheimer's Network (DIAN) research had hinted at the possibility of early diagnosis but with preliminary findings from 128 patients, the evidence seems to be solidifying.
"We had data very early on, but it was based on small numbers of people," said Krista Moulder, associate executive director of the university's Alzheimer's Research Center.
STUDYING PATIENTS WITH GENETIC MUTATION
The study has been tracking sufferers of a unique version of the disease, which results from a specific genetic mutation that represents only about 1 percent of those with Alzheimer's. By testing spinal fluid, doctors can now discover whether the telltale amyloid protein-based plaques that form in the brains of Alzheimer's patients will take shape.
Unlike most cases of Alzheimer's, which are thought to be brought on by a murky combination of genetic and environmental factors, individuals who possess the mutation are guaranteed to show symptoms of the disease eventually, making them a natural control group. Even the age at which the illness will make itself felt is known based on the age when parents began showing symptoms.
While testing at the present time is limited only to individuals with the early onset mutation, Moulder believes that eventually it could have ramifications for other cases as well due to the similarity of both forms of the malady.
"The main difference is in how the disease manifests itself," she said. "They all have dementia. They all have these plaques and tangles in the brain. They all have brain cell death and they all have problems with this amyloid protein being deposited in the brain. So we think that what is learned in these families will have broad application to late onset Alzheimer's Disease."
Moulder said the main difference was in the reason for the amyloid build-up. Those with the mutation produce too much of the substance while the majority of Alzheimer's patients simply aren't moving enough amyloid out of their systems.
She said a colleague compared the problem to a sink filling up.
"You can have the sink fill up because you have the tap on too much and it is overflowing or you can have a clog in the drain," she said. "It seems that people with late onset somehow have a clog in their drain and they can't clear the amyloid as well."
Focus Is On Prevention
Though Alzheimer's has no cure, Moulder notes that there has been a significant shift from treating the disease toward preventing it. That's one reason research on individuals without signs of damage to the brain is so important.
"A lot of the drug companies have been looking at people who are already symptomatic and then trying to treat the symptoms," she said. "We and many other people now believe that that may be too late. By the time someone is presenting with dementia, we know from many people's work that they have already lost brain cells."
Dr. Randall Bateman, Anne Fagan and director Dr. John C. Morris presented the results of the study in France this week.
Moulder said she hopes that the work may lead to treatment trials, something the university is now working on with pharmaceutical manufacturers. The study is set to gain an 11th site soon, and it is hoped the study could expand eventually to include as many as 400 participants.
Moulder said the findings should be of interest to everyone, whether they are genetically predisposed or not.
"We know that the No. 1 risk factor for Alzheimer's Disease is just getting older," she said.
As for Mark Stelzer, the O'Fallon, Mo. resident, who isn't part of the DIAN study and doesn't have the genetic mutation, is optimistic. The progress of the illness seems slow and he's adjusted by writing things down and using a GPS when going out so he doesn't have to recall the route.
"I'm definitely upbeat," he said.
David Baugher is a freelance journalist in St. Louis. To reach him, contact Beacon health editor Sally J. Altman.