Monitoring and Managing ARIA in Antiamyloid Treatments

EP: 1.Donanemab Dosing and ARIA Risk in TRAILBLAZER-ALZ 6

EP: 2.Maintaining Efficacy in Safer Donanemab Dosing Regimen

EP: 3.Importance of Patient Selection and Future Therapies in Alzheimer Treatment

EP: 4.Eligibility and Safety Considerations for Antiamyloid Alzheimer Therapies

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EP: 5.Monitoring and Managing ARIA in Antiamyloid Treatments

At the 2025 Alzheimer’s Association International Conference, held July 27-30, in Toronto, Canada, Alzheimer disease (AD) expert Sharon Cohen, MD, FRCPC, spoke with NeurologyLive^® to discuss the use of emerging AD therapies, specifically focusing on approved antiamyloid antibodies lecanemab (Leqembi; Eisai) and donanemab (Kisulna; Eli Lilly). In this part of the video series, Cohen highlighted key differences between these AD treatments, such as eligibility requirements and safety protocols. She also highlighted amyloid related imaging abnormalities (ARIA) risks and the importance of aligning patient expectations with treatment goals.

In the fifth episode of this AAIC Special Report, Cohen discussed ARIA as a key safety concern with antiamyloid AD treatments. She outlined the 2 types of ARIA and emphasized that although ARIA can occur at low rates in untreated patients, incidence increases with antibody therapy and can vary between agents. Cohen explained the importance of baseline and scheduled MRIs to detect and monitor ARIA before it becomes symptomatic. Despite most ARIA cases being mild and can resolve without long-term cognitive effects, she noted rare instances of severe or fatal outcomes.

Transcript below edited for clarity.

Sharon Cohen, MD, FRCPC: ARIA is the feared adverse effect of these drugs. We need to discuss this potential adverse effect with patients and families to see whether they are comfortable proceeding. There are 2 types of ARIA: ARIA-E, which is edema in the brain or effusions, and ARIA-H, which consists of microbleeds or superficial siderosis.

It’s important to know that ARIA occurs at a baseline low rate in individuals who are not on antiamyloid treatment but who have Alzheimer amyloid pathology. So it’s part of the disease, but the rates go up with the antibody treatment, and they’re specific to the different antibodies, so one shouldn’t conflate across the class. One needs to know, for different antibodies, what the risks are.

In addition to the pretreatment MRI, there is a monitoring schedule for MRIs that are considered mandatory. For example, with lecanemab, that would be before the 3rd, 5th, 7th, and 14th infusion. With donanemab, it’s a little bit different—3rd, 4th, 5th—but again, for each antibody, you want to remember: donanemab is monthly, and lecanemab is biweekly. So if I’m saying before the third infusion, that’s not the same time point depending on the antibody.

What you’re looking for is any new microbleeds, any new ARIA-E, and you’re looking for radiologic severity as well as whether there are any associated symptoms. That will guide whether you can dose through the ARIA, whether you need to temporarily suspend treatment, or whether you need to permanently discontinue treatment. There are tables that will guide the prescriber in terms of how to gauge both—or how to reconcile—clinical symptoms as well as radiologic severity, and what the next steps are. But it’s really important, because most ARIA is asymptomatic, and we want to detect it before it becomes symptomatic. If it’s going to increase, we want to make sure any ARIA events radiologically are stable over time.

Clinicians and patients shouldn’t be overly fearful, because most ARIA is, as I said, asymptomatic, resolves on its own, and doesn’t lead to long-term impairment in cognition. However, occasionally—rarely—ARIA can be serious, severe, and even fatal. So we don’t want to put our patients at risk that way; we want to monitor carefully.

In addition to the scheduled MRIs, there can be unscheduled MRIs. At any time, if the patient develops a new headache, focal symptoms, or something’s not quite right—and this may be a symptom of ARIA—then an unscheduled MRI should be obtained. Again, you can think of patients who are traveling and maybe not in regular contact with their prescribing physician, and whether they are going to be able to access an MRI scan. Those are some considerations.