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I'm gonna now wrap up uh with the last module focused on developing multidisciplinary AIA response protocols for AD anti-amyloid therapy plans. And you touched on this already, so hopefully, this will primarily be a reinforcement. Once again, here are my disclosures. This learning objective is for us to talk about how to implement multidisciplinary REO response protocols, including urgent radiology communication, EMR alerts, and cross-specialty coordination. It's really a team effort, as you said. So, uh, Doctor Benzinger, so when designing your center's monitoring protocol, based on the trial data for both of these medications, about what percentage of ARA cases, cases that, um, uh, are radiographic ARA, would we expect to be asymptomatic and truly purely radiographic? We usually talk about symptomatic cases, but of all the AIA cases, which would you, what percentage would you expect not to be symptomatic, approximately? Great. So it's right around 75%. Um, and again, most of the cases are, um, mild when they are symptomatic, as Doctor Benzinger said. So, um, we talked, Doctor Benzinger presented, uh, this already, but just to reinforce it during clinical trials and in our practice, uh, we see AA, uh, with about the same frequency radiographically as it was reported in, in the trials. But, uh, most of the time, it's asymptomatic and just detected incidentally on the surveillance MRI scan. Um, and, um, RA E is more strongly associated with symptoms than RA H, as was said. And RA H is very rarely associated with symptoms when it occurs in isolation. The thing we're worried about though, as Doctor, uh, Benzinger mentioned, is that, uh, more hemorrhhages could accumulate or a macro hemorrhage may accumulate. So we have to treat that carefully. But it's often not symptomatic. So the common symptoms, as were discussed by Doctor Benzinger, but just reinforced here, uh, headache, confusion, disorientation, dizziness or vertigo, nausea, visual disturbance, fatigue, gait difficulty. A lot of these are pretty non-specific. And so it's important to try to ask the patient and ideally their care partner about How much of a change this is if they had been previously having symptoms. Um, we see this a lot with headaches in particular, where people have had recurrent headaches routinely, but there's something about their headaches now that seem a little different. We tend to have a low threshold for getting MRI scans in that case. And they're usually um not AA. If the person has a previous history of headaches and there's a little Slight change in frequency or severity, um, but we always wanna make sure to check that. Severe symptoms that are associated with aria are uncommon, but can occur, um, uh, in this way, and, and that is, uh, more intense, uh, versions of the common symptoms, especially headache, seizures, status epilepticus, malignant hypertension, encephalopathy or delirium, stupor, or, uh, significant focal neurologic deficits. These can sometimes really closely mimic a stroke. So we, uh, always have to make sure that our emergency room colleagues and our stroke neurology colleagues, uh, have ready access to the documentation that the patient's on one of these therapy plans, uh, so that they know that right off the bat. So, uh, when we can, when we manage the dosing, uh, as Doctor Benzinger talked about in terms of pausing, Um, and, uh, thinking carefully about restarting dosing or stopping dosing, symptoms are usually mild, transient, and self-limiting. Uh, they tend to resolve as RAE resolves. Um, and approximately 80% of symptoms and RAE tend to resolve within about 16 weeks or so. Very rarely, uh, AA can be clinically severe, and this is a, um, very interesting case report that I would encourage everyone interested in this area to read of a neurologist who, uh, essentially figured out his diagnosis himself. Uh, he had initial, um, concerns about memory, uh, got into a trial for an early trial for aducanumab, uh, retired from medical practice. And, uh, all of a sudden developed an explosive headache, fluctuating confusion. Alexia with a a agraphia was hospitalized with uh significant hypertension, admitted to the ICU, uh, and was found to have severe, severe RAE, which you can see here. Uh, you can see the evolution of it and the association between that radiographic finding and his, um, impaired cognitive test performance that as the aria. Um, improved after steroid treatment and, um, anti-hypertensives. He showed improvements and, um, ultimately, uh, resolution of symptoms, but it took a while. It was about a 4-month course. So, this is a, a great case report of uh detailing what can happen with Aria and fortunately, he was able to get through it without more persistent issues. So case 3, is a 64-year-old man with a history of atrial fibrillation status post ablation. He was not an anticoagulation. He had 2 years of progressive memory difficulty, no executive or language symptoms or mood or behavioral or sensory motor symptoms, was able to perform finances and drive without difficulty, very mild functional impairment and symptoms on the quick dementia rating system and the functional activities questionnaire. The past medical history also included hypertension for which he was on losartan. He had a maternal grandmother with late-onset dementia, but no other family history. Physical and neural were within normal limits, and his mini mental was 27 out of 30, but all three items that he missed were word recall consistent with his symptoms. So he was diagnosed with MCI and a progressive amnestic syndrome. Uh, labs for common comorbid conditions were negative, and he had cerebrospinal fluid, amyloid and tau biomarkers that were consistent with plaques and tangles. His MRI showed um mild hippocampal atrophy, physica 1 white matter signal abnormalities, and a negative GRE and he had an AOE 33 genotype. He started the nanumab uneventfully with regard to infusions or symptoms, had 3 infusions, and before each infusion, as is our protocol, the nursing staff documented a negative RES symptom review. So we, we ask our nursing staff to run through a review of systems with each patient and care partner prior to the infusion that they're coming in for. Um, and that includes querying, uh, as Doctor Benzinger said, not just generally, but specifically for, uh, headaches since the last infusion, confusion, vision change, dizziness, nausea, difficulty walking, seizures, altered mental status, facial droop, arm or leg weakness, slurred speech, or difficulty talking. Uh, his RES surveillance MRIs, uh, prior to the 2nd and 3rd infusions were read by neuroradiology as negative and were reviewed and agreed upon by the neurologist, which is our protocol. Um, and the standard template reports were generated, which show the baseline and subsequent number of microhemorrhages and superficial cirrhosis, the size and number of areas of cerebral edema, focal effusion, infarct, or other lesions. So, uh, with each new MRI, There's a cumulative summary of what has been found on prior MRI's, if anything, in these areas, so that you don't have to go back and review more than the most recent MRI to get complete documentation. So, um, what happened then prior to the 4th infusion with his MRI was that, uh, as Doctor Benzinger showed earlier, uh, you can see the beginnings of some aria, E, uh, in several different cortical, 2 different cortical regions. Um, and possibly a third. So, um, this was viewed as moderate RAE and, um, He was seen by a neurology nurse practitioner shortly after the MRI scan. We, we bring people in, um, for uh, uh, either a virtual visit or an in-person visit, uh, as soon as we can after an MRI scan shows this, if the telephone um review suggests the possibility of any, um, symptoms. And so he had reported during the telephone review a, about a week of questions about his left hand being clumsy. Which um had resolved by the time he came to the clinic because when he reported that, we said, we really need to have you come in and do a neurologic exam. Um, he hadn't thought to call about it, um, voluntarily, um, and we see this often. Um, so we continue to take every opportunity to reinforce, uh, what symptoms might be that can occur with Aria and the fact that we have a low threshold for having a phone conversation about whether something that the person is experiencing might be Uh, symptoms consistent with aria. He had a, um, a minimal change in his mini mental, no reported change in cognition or behavior, so his danumab was held, and we planned for monthly MRI's and the, uh, reinstructions, as I just mentioned, were, uh, given. So a month later, as we sometimes see, as Doctor Benzinger mentioned, there was an evolution with the progression of more significant RAE. Uh, somewhat surprisingly, he reported no new symptoms on the