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Welcome to this quick consult podcast. Aria in practice, aligning decisions across the care pathway, brought to you by Medall. This activity is designed to help clinicians anticipate, identify, communicate and manage amyloid related imaging abnormalities, or ARIA in patients receiving anti-amyloid monoclonal antibody therapy for early symptomatic Alzheimer's disease. Before we begin, please review the faculty information, disclosure statements, and learning objectives using the link in the episode description. And remember to claim your CME credit, complete the evaluation link there as well. This podcast is supported by an independent medical education grant from Lily. Joining us today is Doctor Anton Thorstensen, Director of the University of Rochester's Alzheimer's Disease Care Research and Education Program and a leading expert in Alzheimer's Disease care and clinical research. Doctor Thorstensen, welcome and thank you so much for joining us today. Thanks for having me. I'm looking forward to uh exploring these key decisions in the area care pathway. To keep today's discussion practical, we're going to follow Margaret, a 74 year old woman with early symptomatic Alzheimer's disease. She's APOE4 heterozygous. She's completed treatment eligibility assessment, and she's recently started anti-amyloid monoclonal antibody therapy through a memory clinic. Her case will help us explore how ARIA related decisions play out across the care pathway. And what can happen when communication or decision making isn't fully aligned across the care team. So let's start at the beginning of Margaret's treatment journey before ARA ever occurs. Margaret has been counseled about her diagnosis and the potential benefits of therapy. And her daughter is closely involved, but in the pre-treatment discussion, Arya is mentioned only as something the team will watch for on MRI. Six weeks after starting therapy, a surveillance MRI shows new area E. Her infusion is paused. Margaret calls the clinic in distress and her daughter says, we thought this treatment was supposed to help her. Has it damaged her brain? Doctor Thorstensen, where did things start to go wrong here? The issue isn't that ARIA occurred. It is that the patient and care partner, they weren't prepared for what this could mean in practice. So the important thing is to discuss the risk of Aria with the patient and the family member considering amyloid targeting treatment. That requires transparent and balanced communication. That includes about RA E and AA H, that is, uh, brain swelling and uh and microbleeds. The discussion, it should establish realistic expectations regarding both uh radiographic risks, the clinical symptoms associated with aria. And uh the MRI and the clinical monitoring, monitoring schedule. What is particularly important here is the fact that Margaret is an APOE4 carrier. And this means that she has modestly elevated the risk of developing aria as an E4 heterozygote. So it would have been particularly important to set the stage uh right at the beginning for her. The other thing that bothers me here is uh that uh the family somehow found out about this with the clinic not calling them. So they are calling the clinic. So somehow there was a breakdown in uh communication. I think that it is uh important to uh be able to explain that if AA uh happens, If it is minor, just a radiographic and clinically silent, you continue treatment. If it is radiographically moderate or severe, or if there are clinical symptoms, you may take a pause and wait, but you intend to restart treatment if the symptoms aren't too significant. So use a practical language. If we see certain MRI changes, we may pause treatment. We will monitor this closely, and we will reassess when it is safe to restart. The other thing that I think is critical is that the patient and family knows exactly who's in charge, who's leading the treatment here. They need a named contact. They need written materials so that they know whom to call and especially in a situation of crisis. So an information card, sometimes called patient alert card, is much advisable. In a busy clinic, what should that pre-treatment counseling actually include? It's imperative to explain AIA in plain language. You should point out that there are two main findings on MRI monitoring, and that includes RA E or localized brain swelling, and AA H. Those are usually small areas of bleeding, either microhemorrhages. superficial cirrhosis, which is more like a smudge, and in very rare cases macro hemorrhages. These symptoms may or may not cause symptoms. And uh, uh, three-quarters of AA is only seen on MRI monitoring and the symptom-free. Most often when symptoms are present, they're mild to moderate, but in rare occurrences, those symptoms can be severe. So it is imperative also to clarify the monitoring schedule that it includes serial MRIs at certain set points and also clinical monitoring when, where people will be asked about the most common symptoms. These include new headaches or the change in the type or pattern of headaches, confusion, visual changes, dizziness, weakness, gait instability, uh, speech disturbance, and in rare instances, uh, seizures. So, before AA can occur. Every patient and care partner should know what AA is. What symptoms matter and what a treatment pause, uh, means. Let's move a little further along Margaret's treatment journey, where her follow-up MRI brings the next set of decisions. So Margaret's RAE is confirmed and the treatment is paused. 8 weeks later, a follow-up MRI shows the RAE has resolved. But the report notes microhemorrhages described as Ar H. The local radiology department uses SWI, susceptibility weighted imaging, as its standard protocol. But the clinical trial grading framework was built on GRE, gradient recalled echo. For the non-radiologist listening, why does that technical difference matter? It matters because these are different sequences and they have different sensitivity to finding microhemorrhages or superficial cirrhosis. So SWI is more sensitive. Uh, one of the critical issues is that, uh, you should work with a set. Imaging center You can never exclude the fact that in an urgency or acute situation that a different imaging center might have to be used, like if someone has to go to the ED. But uh it is uh important to start with uh the same. Sequences, MRI sequences as you're going to use later. For example, SWI is, uh, more sensitive, so it will count more microhemorrhages than a GRE sequence. Particularly troublesome is if, uh, someone is switching between, uh, sequences or switching between machines during the, uh, uh, MRI monitoring. So, um, it is, uh, again, important that the clinical center and the imaging center agree what sequences are we going to use, and you may have to adjust that. And if, uh, for example, SWI is used to expecting that you might find slightly higher.