Alzheimer’s Diagnosis, Management Improved by Brain Scans
First Phase of Nationwide Study Demonstrates Clinical Impact of Amyloid PET Imaging
A first-of-its-kind national study
has found that a form of brain imaging that detects Alzheimer’s-related
“plaques” significantly influenced clinical management of patients with mild
cognitive impairment and dementia.
The study revealed that providing
clinicians with the results of positron emission tomography (PET) scans that
identify amyloid plaques in the brain changed medical management — including
the use of medications and counseling — in nearly two-thirds of cases, more
than double what researchers predicted in advance of the study. The technique,
known as “amyloid PET imaging,” also altered the diagnosis of the cause of
cognitive impairment in more than one in three study participants.
The multicenter study of more than
11,000 Medicare beneficiaries, published April 2, 2019 in the Journal of the
American Medical Association (JAMA), was managed by the American
College of Radiology and led by scientists at the Alzheimer’s Association, UC
San Francisco, Brown University School of Public Health, Virginia Commonwealth
University School of Public Health, Washington University School of Medicine in
St. Louis, UC Davis School of Medicine, and the Kaiser Permanente Division of
Research.
“We are impressed by the magnitude of
these results, which make it clear that amyloid PET imaging can have a major
impact on how we diagnose and care for patients with Alzheimer’s disease and
other forms of cognitive decline,” said study lead author and principal
investigator Gil Rabinovici, MD, Distinguished Professor of Neurology at the
UCSF Memory and Aging Center and member of the UCSF Weill Institute for
Neurosciences.
“These results present highly
credible, large-scale evidence that amyloid PET imaging can be a powerful tool
to improve the accuracy of Alzheimer’s diagnosis and lead to better medical
management, especially in difficult-to-diagnose cases,” added Maria C.
Carrillo, PhD, Alzheimer’s Association chief science officer and a co-author of
the study. “It is important that amyloid PET imaging be more broadly accessible
to those who need it.”
Alzheimer’s disease is characterized
by the accumulation of both amyloid protein plaques and tau protein “tangles”
in the brain, the presence of which are required for a definitive diagnosis.
Until recently, amyloid plaques could only be detected by postmortem
analysis of autopsied brain tissue. With the advent of amyloid PET — which
involves injecting patients with “tracer” molecules that stick to amyloid
plaques and can be used to visualize their location in the brain — it became
possible to detect plaques with a brain scan and therefore more accurately
diagnose people living with the disease.
Though there is no cure for
Alzheimer’s disease, early diagnoses enable physicians to prescribe appropriate
symptom-management therapies, counsel families on important safety and
care-planning issues and direct people to clinical trials for promising new
drugs. It also allows people with the disease and their families to plan for the
future, including legal and financial issues, and accessing resources and
support programs. PET imaging results that reveal no signs of amyloid buildup
in the brain rule out Alzheimer’s disease as the cause of memory loss, which
can prompt an evaluation for alternative and sometimes reversible causes, such
as medication side effects, sleep or mood disorders and other medical
conditions.
However, despite FDA approval of
amyloid PET tracers, use of amyloid PET imaging to assist with the accurate
diagnosis of the cause of someone’s dementia is currently not covered by
Medicare or health insurance plans, making it unavailable to most people.
Launched in 2016, the four-year Imaging Dementia –
Evidence for Amyloid Scanning (IDEAS) study was developed by a team
of scientists convened by the Alzheimer’s Association to determine whether
learning the results amyloid PET imaging would change medical management and
health outcomes of people with memory loss and cognitive decline. IDEAS
recruited nearly 1,000 dementia specialists at 595 sites in the U.S. and
enrolled more than 16,000 Medicare beneficiaries with mild cognitive impairment
or dementia of uncertain cause. Under their Coverage with Evidence Development
policy, the Centers for Medicare & Medicaid Services (CMS) reimbursed
amyloid PET scans conducted at 343 facilities and interpreted by more than 700
imaging specialists as part of this clinical study.
“This was a uniquely real-world study
that looked at the impact of amyloid PET imaging in community clinics and other
non-academic settings, and demonstrates for the first time how much impact this
technology has in real-world dementia care,” Rabinovici said.
The newly published results from the
first phase of the IDEAS study focused on how amyloid PET scans altered
physician diagnosis and treatment plans for the 11,409 participants who
completed the study. As the study’s primary endpoint, the scientists collected
data on how physicians altered participants’ medication prescriptions and
counseling about safety and future planning. As a secondary endpoint, the
researchers evaluated whether PET imaging results caused physicians to alter
participants’ diagnoses. Finally, several exploratory endpoints included
physician decisions about referrals to Alzheimer’s clinical trials.
The newly published data reveal that
physicians changed their clinical management of more than 60 percent of
patients in the study, more than double the number the authors had predicted in
advance.
In participants who joined the study
with mild cognitive impairment and whose brain scans revealed the presence of
significant amyloid deposits, clinicians were twice as likely to prescribe
Alzheimer’s drugs following PET imaging (~40 percent prior to imaging vs. ~82
percent following imaging). In those with dementia and significant amyloid
buildup on PET scans, prescriptions of these drugs rose from ~63 percent to ~91
percent after the study. Doctors discontinued the use of these drugs in some
patients whose scans revealed little amyloid deposition. In addition, for
approximately one quarter of study participants, physicians changed
non-Alzheimer’s drug prescriptions and counseling recommendations based on PET
imaging results.
PET scans that revealed no significant
amyloid buildup led physicians to rule out Alzheimer’s disease for
approximately one in three patients who had previously been given an
Alzheimer’s diagnosis. On the other hand, PET scans that showed
significant amyloid plaque buildup led to a new diagnosis of Alzheimer’s
disease in nearly half of patients who had not previously been diagnosed with
the disease.
The researchers also discovered that
one-third of participants who had previously been referred to Alzheimer’s
clinical trials showed no sign of amyloid buildup based on PET imaging, which
generally rules out Alzheimer’s disease as the cause of their cognitive
symptoms. Based on the imaging results, physicians were able to ensure that
nearly all patients referred to Alzheimer’s trials were amyloid-positive (93
percent), which is critical to these trials’ success.
“Accurate diagnoses are critical to
ensure patients are receiving the most appropriate treatments. In particular,
Alzheimer’s medications can worsen cognitive decline in people with other brain
diseases,” said Rabinovici. “But perhaps more fundamentally, people who come
into the clinic with concerns about memory problems want answers. An early,
definitive diagnosis may allow individuals to be part of planning for the next
phase of their lives and to make decisions that otherwise would eventually need
to be made by others.”
The IDEAS team is currently analyzing
data on the study’s second phase, which will examine how amyloid PET scans
affect health outcomes following the scan. The researchers are using CMS claims
data to document hospitalization rates and Emergency Department visits for
IDEAS participants, and comparing them to participants with similar neurologic
problems but who did not undergo amyloid PET. They plan to publish their
findings in 2020. In addition, the researchers are developing a second study
(known as New IDEAS) to include more people with both typical and atypical
clinical presentations of Alzheimer’s and recruit a study group that better
reflects the racial and socioeconomic diversity of the national population.
IDEAS Study Leadership: Rabinovici and Carrillo are co-chairs
of the IDEAS Study along with Constantine Gatsonis, PhD, of Brown University
School of Public Health; Bruce Hillner, MD, of Virginia Commonwealth
University; Barry Siegel, MD, of Washington University School of Medicine in
St. Louis; and Rachel Whitmer, PhD, of UC Davis School of Medicine and the
Kaiser Permanente Division of Research, in Oakland, Calif. See the study
online for a full list of authors and affiliations.
Funding: The trial was
funded by the Alzheimer’s Association; the American College of Radiology; Avid
Radiopharmaceuticals, Inc. (a wholly owned subsidiary of Eli Lilly and
Company); General Electric Healthcare; and Life Molecular Imaging (formerly
Piramal Imaging). PET scans in the study were reimbursed by the Centers for
Medicare and Medicaid Services (CMS).
The IDEAS Study was developed in
response to CMS’s 2013 National Coverage Decision on amyloid PET imaging in
dementia and neurodegenerative disease (CAG-00431N) to not cover these scans
for Medicare enrollees. CMS reimbursed amyloid PET scans for participants in
the IDEAS study under its “coverage with evidence development” program. The
purpose of the coverage with evidence development program is to gather
additional evidence to inform a future coverage decision.
Disclosures: Rabinovici has
served on scientific advisory boards for Genentech, Eisai, Merck and Roche. He
receives research support from Avid Radiopharmaceuticals and Eli Lilly and
Company; and serves as associate editor for JAMA Neurology. Siegel is an
advisory board member for GE Healthcare and Blue Earth Diagnostics. He has
received consultation fees from Avid Radiopharmaceuticals, BTG Management Services,
Capella Imaging, Curium Pharma, and Merrimack Pharmaceuticals; and has received
clinical trial support from Blue Earth Diagnostics and Progenics
Pharmaceuticals. Siegel’s spouse is a speaker for Siemens Healthineers. All
other authors report no relevant disclosures.
About UCSF: UC San Francisco (UCSF) is a leading
university dedicated to promoting health worldwide through advanced biomedical
research, graduate-level education in the life sciences and health professions,
and excellence in patient care. It includes top-ranked graduate schools of
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renowned programs in basic, biomedical, translational and population sciences;
and a preeminent biomedical research enterprise. It also includes UCSF Health,
which comprises three top-ranked hospitals – UCSF Medical Center and
UCSF Benioff Children’s Hospitals in San
Francisco and Oakland –
as well as Langley Porter Psychiatric Hospital and Clinics, UCSF Benioff
Children’s Physicians and the UCSF Faculty Practice. UCSF Health has
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About the Alzheimer’s Association: The Alzheimer’s Association
is the leading voluntary health organization in Alzheimer’s care, support and
research. Our mission is to eliminate Alzheimer’s disease through the
advancement of research; to provide and enhance care and support for all
affected; and to reduce the risk of dementia through the promotion of brain
health. Our vision is a world without Alzheimer’s®. Visit www.alz.org/facts or
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