Pre-Clinical Alzheimer's Tests Pose Clinical and Ethical Challenges

    • October 13, 2011

Slowly, but steadily, researchers are beginning to discover the secrets to diagnosing Alzheimer's Disease long before symptoms appear. With increasingly sophisticated tools for measuring changes in the brain, physicians may soon be able to offer tests that can predict a person's chances of developing the disease. The discovery is a great step forward in dementia research, but physicians and policy makers are not yet prepared to help patients successfully manage such a diagnosis, advises Robert Wood Johnson Foundation (RWJF), Investigator in Health Policy Research (2008), Jason Karlawish, MD.

"Research is underway that may bring these tests to market as soon as 18 months from now," Karlawish notes, referring to development of the radiotracer florbetapir (Amyvid), which allows for the detection of the protein b-amyloid in the brain. It is currently being considered for Food and Drug Administration (FDA) approval. B-Amyloid creates a plaque in the blood vessels in the brain that is thought to contribute to the development of Alzheimer's Disease. "The real question is once these tests are available, once we label someone as having pre-clinical Alzheimer's, what then?" Karlawish asks. Privacy issues, mental health concerns and guidelines for treatment recommendations may all come into play, because of the stigma attached to an Alzheimer's diagnosis and the lack of an effective treatment for the disease.

Changing How We See Alzheimer's

Providing guidance for physicians, policymakers and mental health professionals working with pre-clinical Alzheimer's patients is the subject of Karlawish's most recent article, "Addressing the Ethical, Policy, and Social Challenges of Preclinical Alzheimer's Disease," published in the October 2011 print edition of the journal, Neurology. "In my essay, which is part of my Investigator project, I examine and make recommendations in specific areas," explains Karlawish, who is also a professor of medicine and fellow at the Institute on Aging at the University of Pennsylvania. "First, the pre-clinical diagnosis is made before a person shows even the most subtle signs of the disease, possibly 10 years before the onset of symptoms. This, of course, reflects the growing trend towards using biomarkers, instead of symptoms, to diagnose a disease. So, even if you're doing research on the biomarker, at some point you're labeling research subjects who are biomarker positive, so how should a researcher disclose this information to a research participant? In my paper, I make the case for up-front screening of study participants for mood disorders and ongoing screening to be sure that they can deal with the potential stress of being labeled as 'biomarker positive,' " Karlawish says.

"In the area of policy, I think we need to establish a national Alzheimer's education program, similar to the National Cholesterol Education Program (NCEP). The idea would be to have an objective advisory committee—comprised of neurologists, geneticists, clinicians and others—which would decide who would be tested for the biomarker, who should receive interventions and the parameters for pre-clinical diagnosis," Karlawish says. "We need to establish what constitutes high risk. We also need guidelines to avoid intellectual conflicts of interest among the experts making these decisions."

Another critical policy consideration Karlawish highlights is the area of privacy. "Right now, many states require that a diagnosis of Alzheimer's be reported so that it can be considered when issuing a driver's license. This should not occur with a pre-clinical diagnosis. We also have to consider the financial and legal implications of early diagnosis."

Reducing Our Dependency on Drug Treatment

While Karlawish acknowledges the need for an effective, evidence-based treatment for Alzheimer's, he encourages policy-makers to also consider the importance of health and environmental policies that may reduce rates of dementia and improve overall public health. "As we begin to diagnose with biomarkers, we run the risk of becoming overly focused on drugs as the answer to health problems like Alzheimer's. But, behavior and lifestyle can make a tremendous difference in brain health. We need to build healthier cities and towns with sidewalks for exercise, access to good food, behavioral incentives and nudges to reduce smoking and head injury. If we only concentrate on diagnostic tests and medications, instead of supporting healthy lifestyles and building healthy environments, we may find ourselves dependent on very expensive, drug-based interventions. Investing in solutions to larger, public health problems is a more cost-effective approach," he says.

The Benefits of Pre-Clinical Testing

Lost in the concerns about the misuse of pre-clinical Alzheimer's testing data, is the far more positive message about the value the tests may offer in the near future. "Though we do not have a treatment or cure for Alzheimer's now, we are living in the midst of a revolution in Alzheimer's care. So, in addition to helping patients engage in behaviors that are brain healthy, we hope that someday, we will be able to treat someone after a pre-clinical diagnosis in such a way that they will live out a healthy lifespan and die with little more than moderate memory problems," Karlawish says. But until then, guidelines are needed for the use of pre-clinical biomarkers for the disease.

To continue to spur discussion and research on how new methods of identifying disease are transforming the practice of medicine, Karlawish is working on a paper on the "triumph of the biomarker and its promise in health and health care," he says.

The Robert Wood Johnson Foundation's Investigator Awards in Health Policy Research program provides funding to highly qualified individuals undertaking broad studies of the most challenging health, health care and health policy issues facing America. Grants are awarded to Investigators from a wide range of disciplines. Their work reflects thinking that is creative and conceptual and crosses disciplinary boundaries in search of knowledge and innovative solutions to critical health problems and policy issues.