A Call to Action: Best Practices for Imaging and Managing Alzheimer Patients
Editor’s note: Moderated by Lawrence Tanenbaum, MD, FACR, Applied Radiology hosted a series of conversations with experts on Alzheimer disease imaging and management at the 2024 Radiological Society of North America Annual Meeting and Scientific Exhibition.
In this discussion Dr Tanenbaum, Suzie Bash, MD, a medical director at RadNet, and Petrice Cogswell, MD, PhD, associate professor of radiology at The Mayo Clinic, Rochester, Minnesota, discussed opportunities and responsibilities facing the neuroradiology community.
Alzheimer disease (AD) treatment is entering an exciting new era, ripe with opportunities for the imaging enterprise. Neuroimaging specialists must understand the role of novel disease-modifying therapies (DMTs); adopt a set of best practices with respect to evaluating and surveilling patients undergoing treatment; and play a greater role in the multidisciplinary care of AD patients.
Advancing Disease-Modifying Therapies: The Role of Imaging
The recent introduction of disease-modifying immunotherapies such as lecanemab and donanemab has shifted the AD treatment paradigm. Mobilizing beta-amyloid deposits in the brain, these monoclonal antibodies have been associated with a 20% reduction in cognitive decline. Efficacy is closely tied to early diagnosis and appropriate patient selection. Neuroradiologists are therefore central to the clinical pathway.
Amyloid PET scans and other biomarkers play a pivotal role in identifying early-stage patients and helping to ensure optimal outcomes. “Patients with early-stage disease—those with lower tau burden—respond best to these therapies,” says Petrice Cogswell, MD, PhD, associate professor of radiology at Mayo Clinic, Rochester, Minnesota.
Managing Risk: Amyloid-Related Imaging Abnormalities (ARIA)
While these therapies offer promise, they also present risk, particularly for the development of amyloid-related imaging abnormalities (ARIAs). ARIAs manifest as edema and sulcal effusion (ARIA-E) or as microhemorrhages and superficial siderosis (ARIA-H). The presence and radiographic severity of ARIA as well as patient symptoms are used to determine a patient’s eligibility for continued drug dosing. Therefore, accurate detection, quantification, and grading is essential for safe patient management.
Suzie Bash, MD, a medical director at RadNet highlighted the importance of carefully monitoring patients. Most patients [won’t have symptoms of ARIA], but it's still critical to be able to identify the ARIA when it does occur so that the infusion can be withheld if it's moderate or severe radiographically, because what you don't want to do is dose a patient on top of a moderate or severe aria and then potentially have it get worse,” Dr Bash says. She emphasizes that neuroradiologists must be vigilant in identifying and grading ARIA, as misinterpretation can lead to adverse impacts on therapy.
Best Practices for Baseline and Surveillance Imaging
Disease modifying therapy requires neuroradiologists to employ rigorous, consistent imaging protocols for patients, beginning with a comprehensive baseline MRI. Baseline, pre-treatment microhemorrhages, such as in the setting of cerebral amyloid angiopathy and other factors such as APOE-4 homozygote status are risk factors for ARIA and used in evaluating a patient’s risk vs benefit from these therapies.
“There must be accurate evaluation of baseline findings such as the number of microhemorrhages. Detection and quantification of interval changes while on therapy is particularly critical,” Dr Bash says. Decisions regarding suspension of therapy depend on ARIA severity and clinical symptomatology. If therapy is withheld, it can be resumed once ARIA-H stabilizes and ARIA-E resolves. Dr. Cogswell adds that surveillance imaging is performed at prescribed intervals during therapy to detect new ARIA, per the FDA labeling. “We're looking for findings of new edema, a new sulcal effusion, new microhemorrhages or superficial siderosis since starting therapy. For accurate detection we need to have a high-quality brain MRI, ideally performed at 3 Tesla, and we need to have the appropriate sequences,” she says.
The key components of a baseline ARIA monitoring brain MRI are:
- Appropriate and dedicated MRI protocols. Consistent imaging approaches across visits and centers are essential to accurately track changes. At minimum, a T2 FLAIR for ARIA-E detection, GRE or SWI for ARIA-H detection, and DWI to differentiate ARIA-E and acute ischemia are required. A routine brain imaging protocol with a 3D T1 may be employed. The most important task is to focus on the parameters for susceptibility imaging. “If the 2D GRE TE is too low, you risk missing microhemorrhages,” Dr Bash notes.
- Field strength. While 3T MRI may be ideal, its availability can be limited and 1.5T scanners are considered acceptable. For larger or claustrophobic/anxious patients who cannot tolerate a cylindrical bore system, open 1.2T systems may be used. Consistency in field strength across visits is particularly impactful.
GRE vs. SWI: Choosing the Right Technique
The choice between gradient echo (GRE) and susceptibility-weighted imaging (SWI) is an ongoing debate. At RadNet, GRE is used for dementia protocols to maintain consistency with clinical trials and resultant ARIA grading scales. “SWI is more sensitive but complicates reporting,” Dr Bash explains. “Using GRE ensures we are aligned with the protocol utilized in the clinical trials from which the ARIA-H grading criteria were established.”
In contrast, The Mayo Clinic employs both techniques, with a preference for conservative reporting based on SWI findings. “Our neurologists want to be as sensitive as possible,” Dr. Cogswell notes. “Even a few additional microhemorrhages on SWI warrant caution.”
Neuroradiologists should work with their teams to determine the best approach for their practice,
Multidisciplinary Collaboration
Effective AD patient management requires close collaboration among neuroradiologists, neurologists, and other specialists. At Mayo Clinic, Dr Cogswell describes a robust multidisciplinary conference where cognitive neurologists, neuropsychologists, radiologists, and social workers review each patient’s case.
“We integrate imaging biomarkers, neuropsychological data, and genetic testing to make informed decisions,” she says.
This team-based approach helps assess the risks and benefits of therapy, particularly in patients with genetic predispositions like APOE-ε4 alleles. Neuroradiologists should actively participate in these discussions to provide imaging insights that can help guide treatment decisions.
Practical Recommendations
There are several steps neuroradiologists can implement to maximize the efficacy of AD treatment. These include:
- Training. In this era of DMT for Alzheimer disease, it is important for neuroradiologists to have dementia imaging pathway training to assist in accurate interpretation of amyloid PETs, baseline MRIs, ARIA surveillance MRIs, and AI-powered quantitative MRI (QMRI). Keep abreast of emerging therapies and guidelines. As new treatments enter the market, understanding their implications for imaging will be essential.
- Regular surveillance. High-quality, standardized interval surveillance MRIs should be used to monitor for ARIA. Consistency in technique and attention to the subtle interval findings is crucial for identifying ARIA.
- Detection and quantification. Document microhemorrhage counts meticulously and clearly communicate therapy-related ARIA changes.
Strive for Excellence
The emergence of disease-modifying therapies for Alzheimer disease represents a pivotal moment for neuroradiology and all imaging enterprise stakeholders. By understanding these new treatments and promptly identifying ARIA; adopting best imaging practices; and becoming team players in the treatment of AD, neuroradiologists can ensure they provide the highest level of care for these patients. “We have an obligation to get this right—for our patients, for our colleagues, and for the future of Alzheimer disease care,” says Dr Tanenbaum.