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My name is Doctor Anton Thorstensen, and I'm a geriatric neuropsychiatrist and memory disorder specialist at the University of Rochester School of Medicine in Rochester, New York. Welcome to Restoring guideline-based Decisions, Alzheimer's Disease therapy pauses, reinitiation, and dose modification. Detection is the start of management, not the endpoint. What I mean by that is that you remember Margaret, the patient that we discussed previously who was undergoing anti-amyloid therapy when she was discovered to have new symptomatic RA E and limited new RAH, that is two new microhemorrhages, on a scheduled MRI. What we, uh, need to do is respond to that. So, We've got to detect the emergence of AI. And uh most AA is clinically silent. So thus, we have, um, scheduled MRI monitoring with the AA uh protocol in terms of the sequences that are included. And they need to be read in the right way so that we can communicate to the clinician who's making the decisions, what is the new event, what are the new findings, and Uh, that allows us to act under the applicable label in terms of is it symptomatic or not symptomatic, is the radiographic severity mild, moderate, or severe. If RE is present, we have to regularly reassess, and that means if it was symptomatic or even if it is silent at the beginning to make sure that clinical symptoms either recede if they were present. Or do not emerge, but also we have to monitor the MRI findings and the resolution of the ARIA E and the stabilization of ARIA 8, that's the microhemorrhages, the superficial cirrhosis, etc. Based on these findings, we have to decide whether to uh resume therapy. Continue the pause or discontinue treatment because of the severity of the findings. So in order for this to be done, we have to be prepared. It needs to be clear where does the responsibility for this decision making lie. So there isn't some sort of paralysis that happens where nobody is making decisions because not making a decision is a decision in itself. What we do know about anti-amyloid therapy is that the benefit Directly relates to the degree of amyloid resolution, how much of the brain amyloid is mobilized and cleared, and that is clearly connected with the dose and the frequency and the amount of completed infusions. So There are 4 inputs that determine the immediate response. Like I said before, is the aria symptomatic or not? Over 75% of RE is clinically silent. But if symptoms are present, it necessitates a pause in treatment, even if the symptoms are mild. How did the symptoms emerge? How are they progressing? And one of the things that I have, uh, uh, tended to do over the years when I manage people with, um, disease modifying treatment targeting, uh, amyloid with antibodies. is to be very thorough in the beginning. What are some of the most common symptoms? For example, headache, and headache is a pretty common symptom. There are people that have their type of headache, mild headache intermittently, and What may distinguish a headache that is associated with new onset aria is if there's a change in the frequency, the nature of the symptoms, or the intensity of the symptoms. How is it progressing? Is it receding and disappearing, uh, or is it getting worse? Uh, for AE. What they determined there is the radiographic severity. Is it mild, where we just have a limited size in one area? Is it moderate, where we may have a limited size in two areas or one slightly larger, or is it severe where the area is quite widespread? The RH or the, uh, bleedings. So, is this microhemorrhages? And uh How many And is this addition to microhemorrhages that were present at the baseline, or was the MRI, the baseline MRI, completely clear and free? And one of the things that we have to think about here is, are we using the same scanner and the same technique? Are we using the same sequences? Because, for example, um, some of the sequences that we use may be more sensitive for RH than others. And if you switch between sequences, you may get the wrong impression. We are also looking for superficial cirrhosis as well as macro bleeds. Mild RAH is basically a 4 or less microhemorrhages. Moderate is 5 to 9. And the severe is 10 or more. For superficial cirrhosis, if we have 1, that is mild, if we have 2, it's moderate, and more than 2, it's severe. We also have to be thoughtful about the treatment context, and that is we've highlighted the importance of alignment. What I mean by that is that we're all on the same page, that the right work has been done right from the get-go in terms of educating the patient and the partner, the care partner, about what to expect. And it's important to clarify the risk of AAE and AAH based on your clinical presentation for this patient, the baseline MRI, the medical history, and the genotyping, particularly if you are an E4 carrier, most importantly, E4 homocyte, you got two copies of 8.4. But Most importantly, you don't want the first conversation about AI to be when it has emerged on an MRI, whether that is regularly scheduled MRI as part of the monitoring or because clinical symptoms emerged. Let's look at the next poll. What should the immediate plan include? I just want to refresh your memory about Margaret. She developed symptomatic RAE and the symptoms were pretty mild. It was just a mild headache. But because of the symptoms associated with the radiographic findings that were relatively mild as well, one area of area E and two new microhemorrhages, but the applicable label directs interruption. But what should the immediate plan include? A, continue treatment, reassess only if symptoms become more severe. B, interrupt for label, assess, schedule MRI for monitoring of the area that is present, and this, uh, both the area E and the AAH and design review ownership. C, discontinue permanently because symptomatic aria predicts future recurrences. D, reduce the dose empirically and keep the original MRI schedule, or E, hold treatment and defer reassessment until the next routine visit. Go ahead and vote The correct answer here is B. Interrupt her label because she had the headache, and the headache was clearly connected temporally.