When doctors see patients who exhibit signs of mild cognitive impairment or dementia, they have traditionally screened them for Alzheimer’s disease using lab tests, mental evaluations, and standard brain scans.
But while these tools provide helpful information, they do not give a conclusive diagnosis. The only way to definitely identify Alzheimer’s has been to examine brain tissue in an autopsy.
New technology involving positron emission tomography (PET), however, has been changing that. The imaging technique can spot amyloid plaques in the brain — a telltale sign of Alzheimer’s — by using a specific radioactive agent that binds to the plaques.
A study published April 2, 2019, in the Journal of the American Medical Association (JAMA) shows how amyloid PET scans may drastically alter how doctors diagnose and treat those with mild cognitive impairment or dementia.
PET Scans Are a More Accurate Way to Identify Alzheimer’s
“Amyloid PET represents a major advancement in that it allows clinicians to supplement their clinical assessment by evaluating direct biological changes of Alzheimer’s in the brain,” says the principal investigator, Gil Rabinovici, MD, a professor of neurology with the Memory and Aging Center at the University of California in San Francisco.
Almost two-thirds of participants in the study had their medical prescriptions and counseling adjusted based on amyloid PET imaging results.
Dr. Rabinovici and colleagues found that PET scans revealing significant amyloid plaque buildup led to a new diagnosis of Alzheimer's disease in about half of patients who had not previously been diagnosed with the disease.
On the other hand, one-third of patients who had previously been referred to Alzheimer's clinical trials displayed no sign of amyloid buildup, which meant that Alzheimer’s was most likely not the cause of their memory and cognitive problems.
Dementia Diagnoses Are Wrong Much of the Time
“The amount of time that dementia experts in the trial were wrong is phenomenal,” says Howard Fillit, MD, the founding executive director and chief science officer for the Alzheimer’s Drug Discovery Foundation, who was not involved in the investigation but uses amyloid PET imaging at his practice in New York City.
“You can imagine the relief that patients and their families have when it turns out it’s not Alzheimer’s disease,” say Dr. Fillit.
Fillit emphasizes that neuroimaging such as this can be an invaluable diagnostic tool.
“If somebody comes into my practice and has memory problems and we’re really not sure what’s going on, this kind of test can be very helpful at defining what’s going on,” he says.
“Some of the people with mild cognitive impairment have potentially reversible causes of their memory problems, or their memory problems will not progress in three to five years to dementia, but then some are going to have Alzheimer’s disease or related dementia and it will progress.”
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Study Followed More Than 11,000 Participants at 595 Practices
For this study, scientists from several colleges and organizations around the United States followed more than 11,000 Medicare beneficiaries with mild cognitive impairment or dementia over the previous four years. The participants had enrolled in the Imaging Dementia — Evidence for Amyloid Scanning (IDEAS) study organized by the Alzheimer’s Association. A total of 946 specialists from 595 practices across the country participated in the project.
Participants were scanned at 343 PET facilities, and these amyloid scans were interpreted by 733 imaging specialists. Amyloid plaques are protein fragments that cluster together and disrupt connections between nerve cells in the brain. They are one of the signature indications of Alzheimer’s, a progressive and irreversible disorder that disrupts thinking, remembering, problem-solving, using language, and other cognitive skills.
An estimated 5.6 million Americans age 65 and older are currently living with the disease, and about 200,000 individuals under age 65 have younger-onset Alzheimer's, according to the Alzheimer’s Association.
Vital Changes in Prescriptions and Counseling Observed
The researchers examined how the healthcare providers changed their patients’ prescriptions and counseling based on the PET imaging, and how the results may have changed their initial diagnoses.
For those individuals with mild cognitive impairment who had significant amyloid deposits on their brain scans, clinicians were twice as likely to prescribe Alzheimer's drugs — such as Aricept (donepezil), Exelon (rivastigmine), and Namenda (memantine) — following the PET imaging.
After reviewing amyloid PET imaging, doctors increased Alzheimer's drug prescriptions for those with dementia and significant amyloid buildup from 63 percent to 91 percent.
In some patients who exhibited little amyloid accumulation, physicians completely stopped the use of these medications. On the basis of imaging outcomes, clinicians also adjusted non-Alzheimer's prescriptions (such as drugs to treat other neurological conditions) and counseling recommendations (such as advice on continued driving and independent living) for about one-quarter of participants.
Rabinovici stresses that it is critical to ensure the accuracy of these diagnoses, because Alzheimer's medications can worsen cognitive decline in people who have other brain diseases.
“Having certainty about diagnosis can help patients and families address these issues more proactively, particularly in early clinical stages, when there may otherwise be ambiguity about the diagnosis and likely progression,” he says.
Why Isn’t Amyloid PET More Widely Used?
The U.S. Food and Drug Administration first approved amyloid PET back in 2012. The process is a simple, routine exam that requires only 10 to 20 minutes in the scanner. The screening takes a total of 60 to 90 minutes because of a delay between injection of the tracer and image acquisition, explains Rabinovici.
But while the technology is widely available across the United States, it is highly underutilized, according to Fillit. “The number of people who have access to this is minuscule when you consider the millions of people who could probably benefit from it,” he says.
Cost is largely to blame. PET scan prices can run between $3,000 and $5,000, and Medicare and most healthcare plans do not cover this type of imaging, according to study authors.
In their National Coverage Decision in 2013, the Centers for Medicare and Medicaid Services (CMS) determined that there was not adequate evidence for clinical utility to justify coverage.
Hopes That the Study Will Lead to Policy Change and Increased Coverage
Rabinovici and his collaborators hope that this investigation and future research will change that policy.
“Our study suggests that amyloid PET has a major impact on management of selected patients,” he says. “Aim two of our study will evaluate whether these changes lead to improved health outcomes. Medicare will assess the evidence from both aims in reconsidering their coverage decisions.”
The study authors noted that this research was limited by its nonrandomized design and lack of a control group. Also, participants were primarily non-Hispanic whites and did not reflect the racial and ethnic diversity of Medicare beneficiaries generally or the U.S. population.
“We are working with Medicare to develop a new trial that will recruit patients with a broader range of clinical presentations and reflect a more racially and ethnically diverse cross-section of the American public,” says Rabinovici.
This is a very promising time for Alzheimer’s diagnosis, according to Fillit. He points to new technologies that are in the pipeline for imaging tau (a protein known to form tangles in the areas of the brain that are vital for memory) and a blood test that may predict the development of Alzheimer’s.
“I think we’ve entered a new age of clinical care and research for Alzheimer’s, and this is just a very exciting beginning,” he says.