If scientists had a test to confirm Alzheimer’s disease, would that have changed the outcome for some treatments that failed to pass scientific muster in clinical trials? Would such a test open doors for future treatments? Alzheimer’s researchers hoping to explore these questions had mixed reactions last week after Medicare recommended that the national health plan for the elderly and disabled only pay for a controversial $3,000 test that detects brain plaque linked to Alzheimer’s in several specific instances—including clinical trials that seek better treatment for the disease. The recommendation, if acted on, could mean more people will learn if they have significant buildup of a protein in the brain associated with Alzheimer’s. But some researchers in the Alzheimer’s community say that the proposed coverage limitation falls short of giving many patients valuable clinical information.
Current science prevents doctors from making a definitive diagnosis determining if a patient has Alzheimer’s until they can analyze the postmortem brain under a microscope during an autopsy and find telltale signs of the disease. During life, physicians typically make a presumptive diagnosis of the disease via a neurological and psychological evaluation that rules out other reasons a patient may have Alzheimer’s-like symptoms (including tumor, stroke or vitamin B12 deficiency).
Last year physicians received a new tool when U.S. regulators approved a test that uses an imaging agent owned by Eli Lilly and Co. that detects a certain kind of protein in the brain. Scientists are still not sure if elevated levels of amyloid beta indicate a patient has Alzheimer’s or if it is merely a symptom of impaired brain function. But if more patients receive the test and are aware that they have a buildup of the protein, theoretically scientists could cast a wider net for research on the disease—including tracking its progression and how, or if, it manifests itself when the plaque is apparent. When previous Alzheimer’s treatments failed during clinical trials, one critique from pharmaceutical companies was that perhaps the data were sullied by patients who had other dementias or reasons for Alzheimer’s-like symptoms rather than the disease.
Implementing this amyloid-imaging test as a requirement for inclusion in trials could potentially strengthen testing because it could weed out individuals without the protein buildup. Already, ahead of last week’s decision, clinical trials were in the works that would use amyloid imaging as an entry requirement. So if Medicare foots the bill for the test, it could help to marginally lower the costs for that research, backers of the test say. But not all Alzheimer’s experts are sold on amyloid’s importance. Whereas some scientists believe that the protein blocks communication between neurons and its presence is a harbinger of disease, others point to work that suggests the predictive powers of the scans are severely limited, given that individuals with normal brain function may also show up with positive scans.
To date, a large obstacle to finding treatments for Alzheimer’s has been identifying patients who are still in the very early stages of the disease. Medicare’s recommendations on when to cover the cost of the test does little to change that, charges Dan Skovronsky, CEO of Lilly subsidiary Avid Radiopharmaceuticals. The draft decision from Medicare did not suggest covering the test in the wide variety of circumstances that were laid out in earlier protocol recommendations from a task force convened by the Alzheimer’s Association, a voluntary health organization focused on the disease. Instead, it said that Medicare should pay the bill for people receiving the test in clinical trials geared toward finding better treatments (and thus those patients would have already been diagnosed through traditional methods and funneled to the trial). It proposed Medicare should also pay for the imaging test in instances where physicians want to rule out Alzheimer's as a diagnosis or when medical providers are trying to distinguish Alzheimer’s from frontotemporal dementia. Currently Medicare does not cover any amyloid beta PET scanning.
Both Lilly and the Alzheimer’s Association issued statements following the decision saying that the proposed level of coverage would not be enough and that funding the test in only those limited circumstances would hamstring patient care. The last word on the coverage is due this fall when Medicare issues its final decision. Whereas private insurance companies often follow Medicare’s lead on coverage decisions, there is no requirement that the companies mirror its ruling.
A negative result from the PET test is actually more informative than a positive result, says Lawrence Honig, an Alzheimer’s expert at Columbia University Medical Center. No buildup suggests it is unlikely that a patient’s neurological condition is a result of Alzheimer’s. And teasing apart when cognitive impairment is due to Alzheimer’s versus another condition such as frontotemporal dementia is important because drugs used to manage Alzheimer’s could have negative side effects for a patient without the disease, Skovronsky says. Neither Alzheimer’s nor frontotemporal dementia has any existing treatment that stops or slows its progression.
The test from Lilly uses positron emission tomography (PET) to detect collections of amyloid in the brain. To perform the test, a radioactive chemical is injected into the body and then taken up by the brain. The chemical, patented by Lilly, temporarily attaches itself to areas of the brain where there is a concentration of amyloid, and the PET scan picks up that radioactive tag. “Ultimately, what we’re trying to find is like a cholesterol test for the brain,” says Gary Small, director of the University of California, Los Angeles, Longevity Center. “If you go to a doctor and you’re over a certain age, a doctor will test your cholesterol. And if it is high, the doctor will give you a statin and lower your risk of heart attack or stroke.” With Alzheimer’s, however, there is no existing treatment to act as the statin if risk is identified earlier.
Ronald Petersen, director of the Mayo Clinic’s Alzheimer’s Disease Research Center in Rochester, Minn., says that physicians should have such amyloid imaging data at their fingertips because it gives clinicians information that differs from other scans. “In reality, it may not change the treatment plan all that much,” Petersen says. “But I still think it’s important to know if that is what is going on. It may motivate people to engage in lifestyle activities that may influence this process and help people plan for the future—though the timing of that planning may be uncertain.”