Anne Kolesar's father, aunt and grandmother all had dementia before they died -- a knowledge that shakes her as she contemplates her future at age 61.
The Indiana, Pa., hospice volunteer has no signs of Alzheimer's disease and no way of knowing if she'll get it, but she's aware that she carries a gene that increases her risk. It means she spends more time than her peers thinking about the disease, and she's joined a national registry of healthy people willing to be studied long-term in trials aimed at preventing Alzheimer's.
Ms. Kolesar and her sister "inspect ourselves minutely to make sure that we haven't got it yet. I know that's the way all children of all Alzheimer's sufferers are -- you're just waiting for it to hit."
Ms. Kolesar, who is married and has an adult son, supports a growing trend in Alzheimer's research, which until now has been dominated by studies of people already diagnosed with some level of the disease that gradually and devastatingly robs them of their memory and cognitive function.
So little has come of efforts to undo those effects in drug trials that more money and emphasis is being put into lengthy monitoring of adults without any dementia symptoms, to see if drugs can postpone their getting the disease or even prevent it. For such studies to be practical and cost-effective, researchers need participants who, like Ms. Kolesar, are known to be at higher risk than the general population.
The primary risk factor for Alzheimer's is age, with an estimated 5 million Americans over age 65 carrying the disease. Ms. Kolesar knows from participation in a prior study in New York, however, that she inherited a gene known as ApoE4, which increases her risk by about fourfold.
That makes her a relatively valuable person among some 20,000 nationally who have signed up for the Alzheimer's Prevention Registry since its creation in May 2012. The Banner Alzheimer's Institute, based in Phoenix, coordinates the registry, hoping ultimately to create a list of 250,000 people making themselves available for study by researchers across the nation.
Jessica Langbaum, Banner associate director, said people 18 or older can join the registry, and they will be emailed updates on Alzheimer's findings and studies. The target population, however, is anyone 50 and older who has shown no problems yet with memory or mental functioning.
About 70 percent of those who have signed up for the registry thus far have some family history of Alzheimer's.
"People certainly feel a personal connection to the disease, and that's often what's motivating them to get involved," Ms. Langbaum said.
The registry has not been used for any studies yet. One of the first will be for a Banner-led trial, funded in part by $33 million from the National Institutes of Health, that will begin tracking the progress in 2015 of some 650 people who carry two copies of the ApoE4 gene.
Only 2 to 3 percent of the population are in that category, and such individuals have about a 20 times higher risk than the rest of the population of developing Alzheimer's, said Eric Reiman, a brain imaging researcher who is Banner's executive director.
The idea is to begin following those 650 people when they're still healthy after age 65 and track them for a five-year period, while administering a drug that has shown potential in preliminary trials to inhibit formation of amyloid plaque. The presence and growth of amyloid in the brain has been linked to Alzheimer's, though researchers have not concluded whether amyloid causes the diminishing mental abilities or are just a visible sign of them.
In a separate long-term prevention trial where the registry won't be needed, Banner is heading a study of hundreds of members of an extended family in Colombia who have a genetic mutation far more serious than carrying the ApoE4 gene. The mutation virtually guarantees that individuals will develop the early-onset version of Alzheimer's in their 30s, 40s or 50s. The family members participating in the study will receive an anti-amyloid drug called crenezumab, or a placebo, while monitored for five years for any preventive effects.
"The hypothesis is that some of these treatments may need to be started before amyloid ravages the brain in order to have the most effect," Dr. Reiman said. "It's been suggested that even a modestly effective treatment could have a profound public health effect. ... A procrastination treatment that delays onset of the disease by five years could cut the number of people diagnosed with Alzheimer's in half."
Two other large prevention trials have received huge attention in the field, and the University of Pittsburgh's Alzheimer's Disease Research Center is expecting to be one of the sites nationally assisting in them.
Washington University is heading a national study of primarily healthy individuals who have the same genetic mutation as in the Colombian family, which virtually assures getting early-onset Alzheimer's. The subjects will be given one of two types of experimental drugs or a placebo for two years to determine what difference they make in developing plaque or symptoms.
A national study based at Harvard University will track 1,000 individuals 65 and older who don't yet have symptoms of dementia even though sophisticated imaging techniques have detected plaque in their brains. For three years they will be given a drug designed to reduce amyloid to see if it is effective in staving off Alzheimer's symptoms.
William Klunk, a University of Pittsburgh psychiatrist and co-director of its Alzheimer's research center, said all of the emphasis on prevention makes sense in light of disappointments that have come before. No drug has lived up to any promising preliminary results in showing it can stop the disease in its tracks, once underway.
"That string of failures has led us to realize it's not going to be a case of just swinging for the fences and hitting a home run that easily," Dr. Klunk said. "Studies now are suggesting it may be a 10- to 15-year period from when the disease starts in the brain to when symptoms first show up. It's not a case of [the] disease being really early when symptoms show up -- it actually may be 10 to 15 years too late."
Any positive results for the public from such long-term trials will be many years away, which can be depressing news for families that have a member already showing dementia symptoms. The Alzheimer's Association nonetheless supports those prevention studies, giving its largest research grant ever, $4.2 million, to support the Washington University study. At the same time, it expects drug trials to continue that examine effects on those who already have mild to moderate symptoms.
"The prevention studies are an expansion, with the hope that in the future we won't have to diagnose anyone with the mild stage of the disease," said Maria Carrillo, the national association's vice president of medical and scientific relations. "We would like nothing more than to be put out of business. That is our goal."
The association has its own registry to make Alzheimer's patients and others aware of treatment trials they can participate in, and it and Banner are helping promote one another's registry. Ms. Kolesar figures there's a good chance any research she becomes part of will be too late to help herself, but hopes it would be valuable for younger people like her 24-year-old son. She's told both him and her husband that she has no intention of living to the end with such a disease, if she starts experiencing symptoms.
She saw how her father went from being a well-respected physician to someone so confused that he was helpless about what to do for his wife when she fell in their home. Living with such diminished capacity, in her mind, would be worse than death.
"I live with something resembling that, the fear that it will happen, but the absolute knowledge that that is happening to you, that you will slowly and progressively be robbed of everything that defines you as a person? No thank you."
To get more information or join the Alzheimer's Prevention Registry, go to www.endalznow.org[1] . For the Alzheimer's Association Trial Match, visit www.alz.org/research[2] /.
First Published October 21, 2013 12:00 am
References
- ^ www.endalznow.org (www.endalznow.org)
- ^ www.alz.org/research (www.alz.org)
- ^ grotstein@post-gazette.com (www.post-gazette.com)
- ^ Get unlimited digital access - web, mobile, tablet, apps and more. (www.post-gazette.com)
