A new, $100 million, four-year study will determine the clinical usefulness and value in diagnosing Alzheimer’s and other dementias through a brain positron emission tomography (PET) scan that detects amyloid plaques, a core feature of Alzheimer’s disease.
The Centers for Medicare & Medicaid Services (CMS) has approved the study called Imaging Dementia—Evidence for Amyloid Scanning (IDEAS). The IDEAS study will test how scanning for brain plaques may affect care and outcomes for patients with dementia or cognitive impairment by clarifying a diagnosis for patients with those conditions.
The national study leadership team includes Rachel Whitmer, PhD, an investigator at Kaiser Permanente Division of Research and an expert on population-based studies of dementia risk factors and outcomes, who shares here the potential impact of the study and its findings.
Q: What are the primary objectives of the IDEAS study?
A: This massive study aims to examine how well amyloid imaging performs in clinics outside the small, rarefied world of clinical trials. IDEAS will measure whether getting a scan can affect the diagnosis, management and future healthcare of people whose cognitive symptoms cannot be definitively attributed to a cause by clinical diagnosis alone.
More knowledge about clinical use of amyloid imaging is important not only for accurate diagnosis of Alzheimer’s, but also for the potential future use of a therapeutic agent. If the study finds that amyloid imaging improves patient outcomes, hopes are high that Medicare may start covering the scan for patients being evaluated for cognitive decline or progressive dementia of unknown etiology.
Q: What is amyloid imaging and what is the association with cognitive decline?
A: Beta amyloid protein in the brain is a defining feature of Alzheimer’s disease, but the effects of beta amyloid on a person’s brain and cognitive abilities are complex. For example, research has shown that up to a third of older people who have no cognitive problems also have beta amyloid accumulations in their brains, and beta amyloid can be present for years before dementia symptoms manifest. It also has not been established what proportion of otherwise healthy people with beta amyloid accretions in their brains will ultimately develop Alzheimer’s disease.
Technological advances over the past decade have enabled detection of beta amyloid deposits in the brain using sophisticated neuroimaging techniques. An example is the use of special tracers, which bind to beta amyloid, in conjunction with positron emission tomography (PET) to measure the amount of beta amyloid in an individual’s brain.
The FDA approved amyloid imaging in 2012, and it promises great potential as a tool for diagnosing various types of dementia and improving care, but there are still many unknowns, some of which the IDEAS study is intended to address.
Q: Why is the IDEAS study needed?
A: Two abnormal structures called plaques and tangles are prime suspects in damaging and killing nerve cells in Alzheimer’s. The plaques are deposits of a protein fragment called amyloid-beta that build up in the spaces between nerve cells. Amyloid PET imaging represents a potential major advance in the clinical assessment of people with cognitive impairment. The technology makes amyloid plaques light up on a brain PET scan, enabling for the first time accurate detection of plaques in living people.
The purpose of the IDEAS Study is to examine how brain imaging, specifically an amyloid PET scan, helps guide doctors in diagnosing and treating Alzheimer’s and other dementias in cases where the cause of cognitive impairment is difficult to diagnose. We believe the study will show that, in diagnostically uncertain cases, knowledge of amyloid status will lead to significant changes in patient management — such as earlier counseling and prescription of more appropriate drugs – that will translate into improved long-term outcomes.
Q: What is the scope and design of the IDEAS study?
A: The study will assemble a registry of more than 18,000 people, Medicare beneficiaries age 65 and older, who have had PET scans and will also select a control group who have not. The CMS will cover the cost of almost 18,500 patient scans from about 200 imaging centers around the country.
Researchers will then gather data for two aims to investigate both the short- and long-term impact of amyloid imaging on patient outcomes.
Aim 1 will examine how a scan might affect patient management in the first 90 days after the procedure, by comparing actual post-scan management to the pre-scan intended management. Outcomes here include the use of Alzheimer’s drugs, other medications, and counseling about safety and future planning.
Aim 2 will use Medicare claims data to compare 12-month medical outcomes between study subjects and matched controls. The primary objective here is to learn whether amyloid imaging is associated with any significant reductions in outcomes such as hospitalization and emergency department visits. Health resource utilization will also be examined.
Q: How will the findings of the study be used? What are the clinical implications?
A: At the end of this study, we will have amassed sufficient data to assess whether amyloid imaging has a positive impact on patient outcomes leading to expansion of beneficiary access to this important procedure beyond the IDEAS study.
An amyloid PET scan costs several thousand dollars. The CMS now wants scientists to show whether amyloid PET imaging pulls its weight in the clinic. To date, CMS has refused to cover PET scans that pick up evidence of amyloid, citing a paucity of evidence that they ultimately improve patient outcomes. IDEAS is a national study that might settle the question. If enough data ultimately point to a patient benefit, CMS may decide to cover scans, at least for some patient subgroups.
We also will generate valuable data on clinical utility that will inform future use of brain amyloid PET as a diagnostic tool, and establish a large group of patients who have had amyloid PET and can serve as a study population to address future research questions.
We will learn a lot about how amyloid imaging functions in the real world and, hopefully, answer the question of where it fits into our current environment of diagnostic and treatment options.
We also believe the study will show that, in diagnostically uncertain cases, knowledge of amyloid status will lead to significant changes in patient management — such as earlier counseling and prescription of more appropriate drugs — that will translate into improved long-term outcomes.
Q: What is your role in the study and where does your expertise come into play?
A: My role began 18 months ago, working with the national leadership team on the design of this massive, seminal study and securing the approval of the protocol as well as the funding from the Centers for Medicare & Medicaid Services.
Over the span of this four-year study, my primary involvement will be leading the second aim in years three and four. We will examine Medicare claims data to compare medical outcomes at 12 months for patients enrolled in the study with a matched control cohort of patients who have never undergone amyloid PET imaging. The primary objective will be to determine if amyloid PET testing in the amyloid PET-known cohort of patients is associated with a significant reduction in major medical outcomes, including hospitalizations and emergency room visits. We’ll also investigate how the scans impact use of other health care resources and services.
These outcomes will largely determine whether CMS will cover amyloid PET scan for members of the general population who have an uncertain diagnosis. It’s our responsibility to demonstrate that such scans provide benefit in terms of patient outcomes.
Q: Why is an accurate Alzheimer’s diagnosis so important?
A: An early and accurate diagnosis is best for many reasons. A diagnosis removes some of the ambiguity associated with cognitive impairment symptoms, allowing people to better understand changes they’re experiencing, maximize their quality of life, and clarify planning for the future.
If a scan is positive, a clinician should be able to provide the patient and family with not only a care plan, but also family planning for the future, and participation in clinical trials. If a scan is negative, a physician may then explore other reasons for the dementia symptoms, which can lead to an accurate diagnosis and better care plans. A more accurate diagnosis can also ensure better care to manage a person’s other diseases and medications to ensure positive health outcomes and quality of life.
The underlying principle is that if you get a specific diagnosis early, you may be able to prevent a bad outcome. For instance, if you knew your mother had minor cognitive impairment due to Alzheimer’s, you might make sure she no longer takes her prescribed insulin or warfarin by herself and potentially ends up in the emergency room with low blood sugar or a hemorrhage. You might take less action if the doctor did not explain what was going on because he was uncertain.
In those scenarios, our system of care is reactive. We wait until a health emergency has occurred. Being proactive and trying to prevent these bad outcomes is the motivation behind this study. With a definitive diagnosis, patients can receive better counseling about safety, advance directives, driving and taking medication.
Other participants will receive negative results that prompt their physicians to search for potentially treatable causes for the cognitive impairment, such as a sleep disorder or depression. Without the scan it might have been attributed to Alzheimer’s and no further workup would be done.
Q: Is there anything else you’d like to add?
A: Just that to be a part of this huge seminal study — which will be basis of many additional studies — is very exciting, and it’s an honor to be asked to participate in such a major role. The field is exploding right now and it’s an exciting place to be.