In July 2023, the U.S. Food and Drug Administration made a long-anticipated decision that will potentially bring new hope to millions of Alzheimer’s patients. The regulatory body granted traditional approval for a therapy that modifies the course of the neurodegenerative condition, rather than just alleviating its symptoms. European regulators are currently reviewing the same therapy, which consists of a monoclonal antibody targeted toward pathological amyloid, and are expected to make a decision soon.
While there is plenty of optimism over the potential of the antibody therapy to treat patients in the early, mild stages of the condition, clinicians also need to ensure its safe use. One fresh challenge for radiologists is recognizing, managing, and communicating phenomena called amyloid-related imaging abnormalities (ARIA), the brain edemas and microbleeds that are potential side effects of these therapies.
Although ARIA are usually asymptomatic, Professor Frederik Barkhof*, professor of neuroradiology at the UCL Queen Square Institute of Neurology, in London, is urging vigilance around these side effects. “Clinicians should understand that the drugs are there, and they work,” he says. “But the monitoring aspect — including appropriate diagnosis and understanding contraindications — is just as important.”
From right to left: Professor Alexander Drzezga, Anja Mett & Professor Frederik Barkhof
At the 2024 European Congress of Radiology in Vienna, Barkhof explained to delegates how to recognize the telltale features of ARIA in magnetic resonance (MR) images, and how to communicate their findings. One priority for him is allaying the anxieties of radiologists who might be encountering ARIA findings for the first time. “On first sight, ARIA can look like a serious vascular problem or infection,” he says. “But they need to be familiar with these phenomena and not get scared, because ARIA are manageable, for example by adjusting the [therapeutic] dose, and better understanding who is at risk.”
GE HealthCare, which helps support the entire Alzheimer’s care area, from diagnosis to therapy, planning and delivery, and monitoring with its comprehensive suite of products and solutions, is uniquely positioned to play a role in ARIA recognition and management. Before starting amyloid-reducing therapy, Alzheimer’s patients could get a positron emission tomography (PET) scan to confirm the presence of the pathology. After this initial diagnosis, they would then require at least four MR scans in their first six months of treatment, consisting of one baseline scan and a minimum of three monitoring scans. These safety measures will require increased capacity of MR systems and the need for increased efficiencies, which GE HealthCare is prepared to support.
“We’re ensuring that the right patients get access to not only the therapy, but everything possible to ensure the safe use of these drugs, which is where imaging really helps,” explains Anja Mett, global product leader of neurology for the pharmaceutical diagnostics business segment for GE HealthCare.
Optimism over new therapy
Every three seconds, someone in the world is diagnosed with dementia. There are currently more than 55 million people worldwide living with dementia, and this number is expected to almost double every 20 years, reaching 78 million in 2030 and 139 million in 2050.
Scientists believe that abnormal levels of beta-amyloid in Alzheimer’s patients, as well as another protein called “tau tangles,” cling together and disrupt the function of neurons. Studies have shown that the new therapy, a monoclonal antibody that is administered once every two weeks via intravenous infusion, binds to beta-amyloid plaques and reduces them over time, thereby slowing down the loss of cognitive function. The most common side effect of this treatment are ARIA.
“On the positive side, these antibodies are really good, and they do what they’re supposed to do,” says Barkhof. He adds that there is a link between prompt treatment and improved outcomes. “If patients already have a lot of atrophy and tissue loss showing up on their MRI scans, they’re very unlikely to regain their functions, because there’s too much brain damage already,” he says.
Confirmation of beta-amyloid pathology is required before treatment with the therapies. There are different tests available. Radiologists often use PET imaging, which involves injecting patients with an imaging agent that helps to visualize beta-amyloid plaques during PET scans of the brain. “These compounds contain a safe amount of a radioactive isotope, and the signal from the isotope will be detected by the PET camera,” says Mett. “That creates an image of the extent and location of the amyloid plaques in the brain,” she adds.
In addition to the diagnostic amyloid PET scan, at least four MR scans are required before and during treatment with the therapy for monitoring purposes. It is during these post-therapy scans that radiologists should stay vigilant to ARIA, says Barkhof. “The therapies cause an inflammatory reaction that leads to amyloid removal,” he explains. “But if this happens too quickly, patients might get a sort of inflammatory response that leads to brain edemas, or small hemorrhages.”
These phenomena, which show up as brighter areas or imaging abnormalities on MRI scans, are usually not serious. Even so, their presence can cause alarm for clinicians and require further monitoring in the form of follow-up MRI scans. If the edemas appear to worsen, or if the patient experiences symptoms such as dizziness or headaches, then an interruption or a halt to dosing may be required, as these could be life-threatening.
“MRI scans need to be interlinked with the infusions and happen at very specific points in time,” says Mett. “If there is cause for concern, there needs to be very close communication between clinicians to ensure, for example, that infusions are halted, and allow for the side effects to resolve.”
Barkhof is advising radiologists to understand the concepts of ARIA sooner rather than later, since the demand for additional MR scans will increase with wider use of the new therapies. He’s also laying down the gauntlet to the broader healthcare industry. Keeping pace with demand, he says, “is only sustainable if we can speed up the acquisition techniques or shorten the examination duration, and facilitate automated detection of side effects like ARIA,” he says.
GE HealthCare has been preparing for moments like these for more than a decade. Its technology, including advanced MR, PET scanners, and the amyloid imaging agent, enables the company to be a solution provider at every stage of the care pathway. Radiologists can harness digital/AI solutions such as AIR Recon DL for MRI, MotionFree for PET/CT, and Propeller for MR and PET/MR to help improve image quality and reduce scan time.
“We’re either working on these challenges or already have these capabilities in our imaging equipment,” says Mett, “along with accelerating image acquisition and ensuring image quality is very high. We’re determined to give clinicians the support needed to confidently interpret images.”
The potential to support clinicians to improve the detection, management, and monitoring of side effects for the new therapies, as well as contributing to the possibility for patients to live happier and healthier lives, is an opportunity that GE Healthcare is proud to be part of.
*Professor Frederik Barkhof is a paid consultant for GE HealthCare. The statements by Barkhof described here are based on his own opinions and on results that were achieved in his unique setting. Since there is no “typical” hospital, and many variables exist — such as hospital size, case mix, etc. — there can be no guarantee that other customers will achieve the same results.
