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My name is Tammy Benzinger, and I am a professor of neuroradiology at Washington University in Saint Louis. These are my disclosures. Um, I do have research support primarily from the NIH, but I participate in, um, clinical trials from a, a number of pharma companies and I've been a consultant as well. So, um, what we're talking about today are designing individualized treatment plans for early Alzheimer's, balancing patient caregiver goals with ARA risk mitigation strategies, um, applying shared decision-making principles. Um, what I'm gonna go into in more detail now is accurately detecting and classifying early ARRA, both the edema, ARAE, and the hemorrhages, AAH. By MRI or by symptom recognition. The integration of dose modification tactics and MRI scheduling protocols into treatment plans for patients on anti-amyloid therapies, and then we'll wrap up with Dr. Dickerson again talking about the implementation of multidisciplinary RAA response protocols, including urgent radiology communications, um, electronic medical record alerts, and cross-specialty coordination. So detection of aria. So, um, accurate detection and classification of early RA E edema and H hemorrhages on MRI or by symptom recognition. This is our first polling question. A neurologist reviews a routine follow-up MRI for a patient on anti-amyloid therapy who reports no new symptoms. The scan reveals two separate areas of flare hyperintensity, vasogenic edema in the right frontal lobe and in the left occipital lobe. Based on standard radiographic grading criteria, how is this finding classified? Your choices are A, Moderate aria E, B, mild aria H, C, moderate aria H, D, severe aria H or E, um, not Araria. This is separate pathology. Thank you for that response. All right. Let's dive into this in a little more detail. So ARIA is amyloid-related imaging abnormalities. And it's um identified in patients who are, have Alzheimer's disease, treated with anti-amyloid immunotherapies. This was first described for bapesuzumab, um, and it is most commonly asymptomatic. When people do get symptoms, they can be really vague. Most commonly, they're things like headache, confusion, vision changes. And um it's important to note that in the United States, the FDA labels for the drugs that have been approved in this category all include recommendations for baseline and serial MRI monitoring to look for radiographic or imaging findings of AIA in addition to clinical assessments. And detection of ARIA on the MRI scan changes the clinical management for these patients. Um, one of the things that's important to note is, um, how to differentiate. Whether someone is having symptoms of aria or whether they're having an infusion reaction. Um, and so just to, to dive into that a little bit. So, um, usually aria has a, a delayed onset. So if you're, if someone's at the infusion center, um, or just had an infusion that day and they're having symptoms, it's more likely an infusion reaction. As I mentioned, the, the symptoms of REA are usually headache, confusion, a focal deficit, or in, in a serious case, seizures, versus infusion reactions would be fever, chills, flushing, nausea, flu-like symptoms, things you would anticipate from an IV medication. On the imaging for symptomatic aria, we're going to see edema and effusion, and hemosiderin or blood deposition, and I'll show you some examples of that in detail. Versus an infusion reaction, we'll have a normal MRI scan. And then the management of it is different as well. So, um, for symptomatic aria, the management is to hold the therapy and treat the symptoms and repeat imaging, and we'll go into those algorithms versus infusion reactions are treated based on that infusion, like slowing it down, premedication, etc. So I think it's really important upfront to have an idea of if the patient is having symptoms. The timing or temporal relationship of that to the infusion, as well as the type of symptom that they're having. This is an example of the ARIA grading scale. Um, thankfully, for those of us in radiology, the, um, FDA has applied the same grading scale to each of these drugs, so we don't have to learn a new scale of what's mild, moderate, or severe. We do need a baseline MRI for comparison because some of these changes, particularly in the mild category, are really subtle. So if you look um in the image on the top left, this is an example of a mild RAAE, just that tiny bit of flare, hyperintensity showing up in the right occipital lobe. Um, moderate becomes either, um, one location that's more than 5 centimeters or more than one location. So here we have bilateral occipital. And then finally, severe is if you have this vasogenic edema, so sparing the cortex predominantly, and it's more than 10 centimeters. And that 10 centimeters. would be in any dimension. So, you have to make sure to think about it if it's going up, down, right, left. And for this reason, a lot of people will actually um employ 3D imaging using this flare sequence to try to better capture it. Although, um 3D imaging is not Required by the consensus guidelines. And this, this is from an article from the American Journal of Neuroradiology where the protocols are published and people can get to those if they have questions. Um, REAH, this is, um, microhemorrhages. And the key here is we, what we care about are, once they're on therapy, are microhemorrhages that have, that are new since the start of treatment. Um, and so, you know, if you had 3 microhemorrhages before you started treatment, and then 3 new ones, that would still count as 3 on therapy, so it would be in the mild category. Um, but here you can see they're very, very subtle, and the specific sequences for detecting microhemorrhages in the clinical trials used a gradient recalled Echo T2 star. And more sensitive sequences people often deploy now in clinical practice are called SWI or susceptibility-weighted imaging. REAH is also can be in the form of what we say call superficial cirrhosis. So this is when you have blood products or hemosiderin deposition in the subarachnoid space. So these are actually signs of small subarachnoid hemorrhages. This is, um, to many of us, probably the, one of the most scary findings on the imaging. And so for this reason, as few as 2 focal areas can move you to the moderate stage and more than 2, you automatically move into this severe category. So very, very serious and important to identify. Um, the MRI's are on a schedule because most of these patients are asymptomatic. And again, we're grading the imaging based on the imaging. I'm gonna say that 3 times in a row, um, because this is one of the most common mistakes I see radiologists make is they, um, they'll see a finding of 2 areas of flare hyperintensity. So for example, that would be a moderate RAE. And then, instead of calling it AA, they'll say, um, go check for symptoms, classify this or that, but really, it's very important that we accurately apply the grading scale for the imaging on the images because the symptoms get integrated into that separately. So, um, this was a, a nice breakdown of this that was published in the, um, JPAD by Doctor Cummings et al. So just to walk you through this area management algorithm. So we have to start with that baseline MRI as Doctor Dickerson has outlined for us. So we need to make sure there are no exclusion factors, like multiple microhemorrhages at baseline. So if they have 5 or more at baseline, that's a red flag. Or um other causes for their impairment. So multiple infarcts, for example, could be that uh vascular dementia may be a more important reason to understand their impairment. Um, We, um, basically, if you get the MRI then, and you do detect REA, and again, it's graded based on the MRI alone, after that MRI grading comes the branch point of whether it's symptomatic or