Bulletin

New Test Could Help Detect Alzheimer’s Disease

Who should get it?

by: Katharine Greider | from: AARP Bulletin |

En español | At an international conference on Alzheimer's disease in Honolulu yesterday, a small Philadelphia-based company presented data on a radioactive dye that promises to be a powerful new tool for penetrating the mysteries of the disease.

Used in conjunction with a PET scan, the radioactive "tracer" is injected into patients, where it quickly binds to sticky plaques in the brain that have long been considered a hallmark of Alzheimer's disease.

The plaques appear brighter on the scan-an image of changes in the living brain once observable only under a microscope at autopsy.

Results presented by the PET tracer's maker, Avid Radiopharmaceuticals, demonstrated at least a 97 percent agreement between the labeled brain scans and pathology examination at autopsy in the diagnosis of Alzheimer's, according to Michael Weiner, M.D., director of the Center for Imaging of Neurodegenerative Diseases at the San Francisco VA Medical Center, who attended the talk.

In a companion study examining the brains of young people not expected to have Alzheimer's, none had a positive scan. "Overall the results are very good," says Weiner, who also is principal investigator of a major government-industry research initiative to determine the best methods for observing Alzheimer's in clinical trials. "The results confirm the view that scanning with an amyloid PET scanning agent is going to detect amyloid in the brain."

Being able to "see" the plaques, made up of a sticky protein fragment called beta-amyloid, gives researchers a new window into the disease process and helps them track the effects of experimental Alzheimer's drugs on the brain.

If the new tracer is approved for marketing by the U.S. Food and Drug Administration-Avid, expects to apply within months-it also will be available to doctors around the country. There's little doubt that Avid's tracer, and perhaps similar ones in development, are a boon to Alzheimer's research. But it will take some time before doctors know what role the scan can play in answering the more immediate questions from patients worried about memory loss or other symptoms of mental decline.

What the test tells us

"We don't exactly know what the clinical use of these scans will be," says Weiner. "We don't know their predictive value."

Indeed, perhaps the most pressing research question the scans can help to answer is the precise role of the amyloid plaques themselves. They are always present in the brains of people with Alzheimer's. But do they cause the dementia and other problems connected to the disease? Some researchers are convinced the culprit is a different kind of amyloid-floating clumps-rather than hardened plaques.

It's not clear, for example, that a 75-year-old person with emerging memory problems and a positive scan showing amyloid will go on to become severely demented; more than 30 percent of older people with normal mental functions show amyloid in the brain.

But doctors might use the new test to help confirm or rule out a diagnosis of Alzheimer's in patients exhibiting some symptoms of dementia.

A negative scan, says Weiner, could be reassuring. "Let's say I have a person that's having quite a bit of memory problems, but the scan is negative. Well, that's good news. That's very good news. They are very unlikely to show a rapid deterioration from Alzheimer's."

The new tracer scans "should not be used in everybody," says James E. Galvin, M.D., director of the Pearl Barlow Center for Memory Evaluation and Treatment at New York University's Langone Medical Center. He says if the patient has symptoms consistent with Alzheimer's and the doctor is confident of the diagnosis, the scan would add little information.

Its utility, he believes, will be in helping to resolve "diagnostic dilemmas" where symptoms and other findings leave significant room for doubt. And in tracking the effects of experimental drugs.

One more tool to help with a cure

Finding Alzheimer’s early is critical both to discovering treatments that attack the disease—currently there are none—and not just its symptoms. Researchers believe the damage in the brain begins a decade or more before an individual notices symptoms. Indeed, it may be that many experimental drugs have failed to arrest or even slow Alzheimer’s because they came too late; dead brain cells don’t come back to life.

The new amyloid tracer (florbetapir F18) represents only one of several recent advances in techniques for observing Alzheimer’s disease in the brain, says Maria C. Carrillo, senior director for medical and scientific relations for the Alzheimer’s Association, host of the conference in Honolulu. “What’s exciting about our current state of knowledge,” she says, “is that we now understand that early detection is possible. That gives us so much hope.”

Other tests that measure signs of Alzheimer’s—from key proteins in spinal fluid to other kinds of imaging—seem to offer a telling glimpse into the disease at different points along its destructive path through the brain. Each may prove a useful source of information at different stages of Alzheimer’s.

The new tracer builds on scientific pioneering by University of Pittsburgh researchers who developed an agent that helped spotlight plaque in the brain. But their compound has a very short life and can only be used by high-tech research centers. Use by doctors in hospitals and clinics is out of the question.

Avid’s new tracer, on the other hand, lasts long enough to allow its transport from manufacturing sites to scanning clinics, potentially reaching about 90 percent of the country, says company spokesperson Christopher Bunting.

Will it be covered by insurance?

For these new brain scans to enter widespread use, both experts and insurers will need to be convinced that they provide some clear benefit—making it easier for patients to get treatment, for example.

Currently the standard evaluation for possible Alzheimer’s disease includes some type of brain imaging—a CT (computed tomography) or MRI—mostly to rule out other problems such as a stroke or tumor.

The more specialized PET test is used far less often, and is covered by Medicare only for the specific purpose of distinguishing Alzheimer’s from a relatively rare condition called fronto-temporal dementia, which typically produces quite different findings on the scan.

This new test should provide a clear benefit “in terms of accuracy of diagnosis,” says P. Murali Doraiswamy, M.D., a professor of psychiatry and geriatrics at Duke University Medical Center who was involved in Avid’s study of the new tracer. He believes it will prove a “game changer” when it comes to diagnosing the disease and getting patients started on treatments earlier.

Longer life, better studies

A study published last year by researchers at Washington University in St. Louis used the earlier Pittsburgh tracer on a small group of patients and found that mentally normal older adults with a positive amyloid scan were more likely than those without amyloid plaques to develop symptoms of Alzheimer’s.

The finding suggests the plaques are not benign, but it needs to be replicated in larger study groups, says Anne Fagan, a neuroscientist at Washington University and coauthor of this and other key work on the disease. Longer-lasting tracers than the Pittsburgh agent—like Avid’s new agent—could make those studies possible.

Katharine Greider lives in New York and writes about health and medicine.

Who Wants to Know?

Top images are from the brain of a cognitively normal person. The bottom images are from an Alzheimer’s patient; plaque buildup shows up in red. — Martin Palm/Gallery Stock

Many older people who suffer from memory lapses are in no hurry to seek a diagnostic work-up for Alzheimer’s disease. What’s the benefit, they wonder, when the condition is not only terrible in its effects, but inexorably progressive and incurable?

Alzheimer’s experts are working hard to change this perception. “We want people to run toward a diagnosis rather than away from it,” says Eric Tangalos, M.D., codirector of education at the Alzheimer’s Disease Research Center of the Mayo Clinic. A diagnosis, these doctors argue, allows the patient to:

participate in planning his or her own future, including family, financial and legal planning.
take one of a handful of medications to treat the cognitive symptoms of Alzheimer’s. The drugs’ benefits are moderate and transient, but they seem to work best in the early stages of the disease.
join programs and pursue activities that use and reinforce retained abilities, while avoiding disruptive changes that can accelerate decline.
join a clinical trial. Patients in clinical research trials typically get a high quality of care. They may be assigned to receive either a harmless placebo or an experimental treatment. Either way their participation helps advance scientific understanding of the disease.

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Saturday, March 26, 2011