Cost seen as main obstacle for Alzheimer's studies
■ Researchers are establishing a gene bank to help target people at highest risk for the disease.
By Susan J. Landers — Posted Aug. 2, 2004
Washington -- There are barriers to conducting an Alzheimer's disease prevention trial that researchers would like to see at least lowered before the incidence of the disease swells with the aging population and overwhelms the health care system.
Prevention studies in general are costly, typically priced at about $20 million. Those for Alzheimer's carry additional burdens. First, they require the recruitment of thousands of elderly participants. They also involve numerous site visits for extensive psychosocial testing over several years.
Thus, researchers urgently are seeking ways to trim costs and size requirements. The bottom line: People are living longer, and nearly half of those older than 85 will have the disease that now affects more than 4.5 million Americans.
"We are right at the beginning of an epidemic of Alzheimer's disease," said William Thies, PhD, vice president for medical and scientific affairs at the Alzheimer's Assn. "We don't have time to do four sequential 10-year trials because that will be 40 years out, and you are going to have so many people with Alzheimer's disease that you will have bankrupted the health care system."
Researchers for the Alzheimer's Disease Anti-inflammatory Prevention Trial -- ADAPT -- are very familiar with the obstacles facing trial enrollment. ADAPT, which began in 2000, is attempting to enroll 4,000 individuals older than 70 who have a family history of Alzheimer's-like dementia but who themselves are not cognitively impaired. These participants must also be physically healthy enough to participate in a long-term trial and potentially be exposed to two nonsteroid anti-inflammatory drugs. It's a tall order.
"Recruitment has been much slower and much more difficult than anticipated," acknowledged study leader John Breitner, MD, MPH, professor of psychiatry and behavioral science at the University of Washington. "But no one had ever done this before, particularly not with these treatments," he said. "We had nothing to go on but 'guesstimates' as to how much time and effort would be involved for this recruitment."
So far, 2,500 people have been enrolled, and Dr. Breitner and colleagues are applying for another five-year National Institute on Aging grant to continue the pursuit.
Next will come the expense of bringing people in for exams. "We're giving people drugs like ibuprofen and naproxen that are widely believed to be potentially quite nasty. So that means that people will have to come in for medical evaluation."
However, so far, the smaller doses of NSAIDS being given to randomized groups of enrollees seem to result in few instances of gastrointestinal harm. Researchers are hoping they will eventually be able to reduce the frequency of medical visits.
Looking for follow-up options
The Prevention Instrument Project is also exploring more cost-effective ways to evaluate Alzheimer trial participants, perhaps using questionnaires filled out at home, phone interviews or even computer-based evaluations. This project is part of the NIA-supported Alzheimer's Disease Cooperative Study, a network that conducts clinical trials.
"We're trying to find out if we can reduce the need for the participants to come in to the clinic," said Steven Ferris, PhD, director of the Silberstein Institute for Aging and Dementia at New York University School of Medicine and the effort's principal investigator. Fewer visits would result in considerable savings in time and expense.
Some early findings from the project, presented at the recent International Conference on Alzheimer's Disease and Related Disorders, showed that the home-based tests were valid compared with those delivered in the clinic.
Another approach to trimming the number of enrollees needed is to select people who are at the greatest risk for developing the disease, said Dr. Ferris. They could be individuals with a close relative who developed Alzheimer's or those older than 80.
Under this approach, instead of enrolling 5,000 people and following them for five years, researchers might be able to enroll 1,500 people and follow them for two or three years and still end up with a statistically significant result, said Dr. Ferris.
Identifying people most at risk via genetic testing or neuroimaging are other methods under investigation. The Alzheimer's Disease Genetics Study is a nationwide push supported by the NIA and the Alzheimer's Assn. to find genes that play a role in late-onset Alzheimer's, the disease's most common form.
The study's aim is to establish a large bank of genetic material, cell lines and data from families in which at least two siblings have late-onset Alzheimer's. Scientists will use the data bank of about 1,000 families -- 350 have been enrolled so far -- to uncover the risk-factor genes that contribute to late-onset Alzheimer's.
The use of advanced imaging technologies are also being employed to detect functional and structural changes in the brain that might indicate early development of Alzheimer's. Scientists hope that the measurements may be able to identify those most at risk before they develop symptoms in order to more effectively assess the efficacy of drug treatments.
Dr. Thies is eager to see that some promising research identified in animal and epidemiological studies proceed to human clinical trials. This includes suggestions that risk factors for Alzheimer's are similar to vascular disease risk factors such as a high-fat diet, sedentary life style, high cholesterol, high blood pressure and diabetes.