September 10, 2012
An imaging agent called florbetaben, the latest in a series of new dyes for detecting Alzheimer’s at an earlier stage, showed promise in detecting the brain plaques that are hallmarks of the disease.
Earlier diagnosis remains an important goal for people with Alzheimer’s, since treatments may be most effective when they are given before symptoms – and brain degeneration – become established. Accurate early diagnosis is also important for ruling out other diagnoses like depression, drug side effects and other treatable problems that may be contributing to symptoms, and for monitoring the effects of new drugs in the pipeline that one day may lead to a cure for Alzheimer’s.
Currently, an Alzheimer’s diagnosis can be confirmed only by autopsy (after a patient dies), when pathologists examine brain tissue to look for the telltale plaques composed of the toxic protein beta-amyloid. The new methods, using dyes like florbetaben that bind to beta-amyloid, allow doctors to visualize amyloid plaques in living brain cells. By injecting patients with the dye and then performing PET scans of the brain, scientists can detect plaque formation in the brain years before someone dies of Alzheimer’s.
The study, presented at the annual meeting of the American Academy of Neurology in New Orleans, involved more than 200 men and women, some of whom had suspected Alzheimer’s. All were given PET scans using florbetaben, as well as MRI scans, another technique to look for buildup of beta-amyloid plaques.
The researchers found that the florbetaben PET scans were very accurate in determining who actually had Alzheimer’s pathology (amyloid plaques in their brain but not necessarily dementia). The test showed 100 percent sensitivity, that is, all the suspected cases of Alzheimer’s confirmed with the scans were confirmed by autopsy after death. The florbetaben scans also had a 94 percent specificity, meaning that in almost all of the cases in which scans indicated someone did not have Alzheimer’s, the same conclusion was confirmed by autopsy.
“These results confirm that florbetaben is able to detect beta-amyloid plaques in the brain during life with great accuracy and is a suitable biomarker,” said study author Dr. Marwan Sabbagh, director of the Banner Sun Health Research Institute in Sun City, Ariz. “This is an easy, noninvasive way to assist an Alzheimer’s diagnosis at an early stage.”
“Also exciting is the possibility of using florbetaben as a tool in future therapeutic clinical research studies where therapy goals focus on reducing levels of beta-amyloid in the brain,” Dr. Sabbagh added.
Other, related dyes that bind to beta-amyloid plaques and allow doctors to visualize the brain with PET scans are also showing promise for early diagnosis of Alzheimer’s. They include florbetapi, or Amyvid, which recently won approval for use by the Food and Drug Administration.
Another brain scan compound currently in use for Alzheimer’s disease called Pittsburgh compound B also accumulates in areas of the brain high in beta-amyloid. But that compound lasts for a shorter period of time and is available only at a few medical centers across the United States. The newer agents last longer, so researchers hope they can be used more widely, if tests continue to show they are effective.
It is important to note that some people have significant accumulation of beta-amyloid in the brain but do not progress to the memory and cognitive symptoms of Alzheimer’s. These individuals may be protected by a large “cognitive reserve,” which refers to the amount of brain cells and connections that are necessary for normal thinking. This also means that a diagnosis of Alzheimer’s pathology is not necessarily a diagnosis of Alzheimer’s dementia. Some people develop large amounts of amyloid plaques in the brain (Alzheimer’s pathology) without having dementia, though many of these individuals may develop dementia if they live long enough.
Further studies will need to be conducted to determine these tests’ effectiveness. Doctors will also need to be trained in how to use them, so it will likely be years before they become routinely available in most doctors’ offices.
Source: American Academy of Neurology, 64th Annual Meeting, New Orleans, April 21 – April 28, 2012.