[SPEAKER_00]: The following has meant to be for medical education and not formal medical advice.
[SPEAKER_00]: Remember to always consider the patient in front of you, especially with matters that's gray as these.
[SPEAKER_00]: The views expressed in this episode don't reflect the views of any affiliated institutions.
[SPEAKER_00]: Welcome back to Gray Matters, where we unpack how medical management is rarely black or white.
[SPEAKER_05]: And go on lots of deep dives along the way.
[SPEAKER_00]: Hey everyone, I'm Dr. Nick Philano, and today I'm joined by
[SPEAKER_05]: Hi, everyone.
[SPEAKER_05]: I'm Dr. Indu Partha, a general internist and PCP at the University of Arizona College of Medicine and Tucson and Banner University Medicine.
[SPEAKER_00]: Awesome.
[SPEAKER_00]: Welcome back, Indu.
[SPEAKER_00]: And for everyone listening, this is actually episode two of our two-part episode on dementia.
[SPEAKER_00]: OK, so I don't know about the rest of you, but personally, I've been anxiously waiting and wondering what's about to happen with our patient.
[SPEAKER_00]: Because we were just about to break the news of dementia to where we and do.
[SPEAKER_05]: Yes, we sure are.
[SPEAKER_05]: And we definitely left everyone hanging last episode, Nick.
[SPEAKER_05]: You, our listeners, and most of all is wise, our patient who had recently been diagnosed with Alzheimer's disease.
[SPEAKER_05]: And you know what, I have watched plenty of soap operas in my time, and I appreciate the art of the cliffhanger.
[SPEAKER_00]: Definitely a lost art these days.
[SPEAKER_00]: Well, in the spirit of TV, let's do a recap then.
[SPEAKER_05]: All right, you got it.
[SPEAKER_05]: So, last time on Grey Matters, we met my patient, Ms.
[SPEAKER_05]: Wise, who had come in for her routine blood pressure management, but we found her to be really confused with our prior instructions.
[SPEAKER_05]: We realized we had to pivot and look into our cognition, and we found that her mini-cog was abnormal.
[SPEAKER_05]: So we quickly ran our list.
[SPEAKER_05]: Was her hearing okay?
[SPEAKER_05]: We reviewed her medications, her sleep habits and her mood,
[SPEAKER_05]: And then we moved on to the mocha, which was abnormal, but her labs found nothing reversible.
[SPEAKER_05]: And we also learned that it's now standard to get MRIs for patients with cognitive deficits.
[SPEAKER_05]: And unfortunately, Nick, her showed medial temporal lobe atrophy, which suggested a diagnosis of Alzheimer's disease.
[SPEAKER_00]: Wow, that was definitely a lot of great learning, but, you know, it's also still a really tough diagnosis to have to break to miswise in her daughter.
[SPEAKER_00]: And I'm sure their first question is going to be, what can you do for them?
[SPEAKER_00]: I mean, this is a really familiar and difficult place for me personally and into I'm kind of looking to you to throw us all a lifeline here.
[SPEAKER_05]: You bet.
[SPEAKER_05]: So let's get back to it and move to this episode's Deep Dive One.
[SPEAKER_05]: How do we deliver the news of a diagnosis of dementia?
[SPEAKER_03]: So if they're in the earlier stages, I want to be really clear after I've done the work up, you know, at delivering a clear headline that, you know, based on my evaluations and the changes we've seen, I worry you have dementia, and I'm really clear about that.
[SPEAKER_05]: Listeners, that's nurse practitioner, Mary Beth Kubrick.
[SPEAKER_00]: Okay, so I think it's great that she's advocating for us being so direct, but this also kind of feels like a mind feel, I mean, are they going to accept the diagnosis of dementia?
[SPEAKER_05]: Yeah, honestly, even after being a PCP for years, I get nervous about how to broach this topic.
[SPEAKER_05]: We just had a patient and resident clinic who literally yelled at the resident and told her talking about his cognitive issues was totally focusing on the wrong thing and just kept asking, what are we going to do about his pain?
[SPEAKER_05]: And I felt so bad because I could just see his wife in the background totally distressed and embarrassed.
[SPEAKER_00]: Oh man, that's really tough, and you don't get that kind of pushback often when you're breaking other hard diagnoses.
[SPEAKER_00]: So I guess the question here is how are you clear with patients, but also taking a count how ready they may be to hear the diagnosis.
[SPEAKER_05]: I think the goal here that we need to concentrate on is to keep the conversation going so that we're able to deliver the news in a way that they're willing to hear.
[SPEAKER_05]: I mean, we need to remember that the goal is to ensure that we keep a line of conversation open with our patient.
[SPEAKER_05]: saying memory loss instead of the word dementia may sometimes seem dishonest or a cop out, but if it will keep a defensive patient returning for follow-up, I mean, words can matter Nick and we definitely don't want our patient to avoid coming back to CS.
[SPEAKER_03]: I usually start by just asking what they understand about their current diagnosis, so I might say, help me understand what you understand about your brain health or your memory, and that way I'm not repeating things they already know we can move forward.
[SPEAKER_03]: And then I also ask what and how much they'd like to know about what to expect over time, recognizing that some people want all of the information, some people do not want to know what to expect, and that may differ for the person with dementia and the caregiver.
[SPEAKER_03]: You know, the person with dementia may not want to know, but their caregiver wants to know.
[SPEAKER_05]: So I guess what I'm taking away is we often will have to tailor how we deliver the news and sometimes even our word choices, but our core message has to be clear.
[SPEAKER_05]: You have a progressive brain disease and your life in abilities are going to be impacted over time.
[SPEAKER_03]: I also, you know, really like to explain to patients what's mentioned in their caregiver that dementia is a spectrum and that each person is gonna progress differently over time.
[SPEAKER_03]: I think some people really lock on to this aspect and think it should be exactly that progression, but we know that some people progress more quickly and some more slowly depending on a variety of factors and what are not they have a new medical exacerbation that might speed up their trajectory.
[SPEAKER_05]: We began our discussion with Ms.
[SPEAKER_05]: Wise by just asking her.
[SPEAKER_05]: Are you having any problems remembering to take your medicine and how are you handling your day-to-day life at home?
[SPEAKER_05]: She told us she was actually having trouble with her medications.
[SPEAKER_05]: Sometimes just taking the matter of her pillbox and holding onto them, unsure if she had already taken them.
[SPEAKER_05]: And she expressed a lot of frustration and annoyance at herself and just told us, I just can't seem to do it all by myself anymore.
[SPEAKER_05]: What is going on?
[SPEAKER_00]: I mean, that sounds really hard for her, but it also sounds like a potential opening for your conversation, right?
[SPEAKER_00]: I mean, you can say maybe one reason you're having so much trouble at home is because of this diagnosis that we think you have, Alzheimer's disease.
[SPEAKER_05]: Yeah, we thought so too.
[SPEAKER_05]: After getting her permission, we called Miss Wise's daughter, and let her know that her mom had been diagnosed with dementia based on our cognitive testing and the MRI results.
[SPEAKER_05]: And her daughter understood, and really just wanted to get her mom as much help as soon as possible.
[SPEAKER_03]: I've also used just a simple graphic a graph that essentially has a progressive downward friend so that you can kind of point here's where I think you are now.
[SPEAKER_03]: I think that just really helps emphasize that this is a chronic progressive disease that will get worse over time and that they'll need more help with fast and daily life.
[SPEAKER_03]: And I like that a lot of those tools really focus on function so that we know what somebody's able to do and how those things may change over time.
[SPEAKER_00]: That reminds me of how an episode 1, Dr. Perry like and dementia to aging in reverse.
[SPEAKER_00]: You know, you acquire skills as you age, and then if you have a diagnosis of dementia, sadly, you start to lose them in the reverse order.
[SPEAKER_00]: I think knowing this, like just having some expectation of what might be to come, can really be valuable for patients in their families.
[SPEAKER_00]: Although, isn't it true that, like, how fast someone's going to progress through those stages?
[SPEAKER_00]: Isn't it very predictable?
[SPEAKER_05]: It really isn't, and I wish there was a template we could follow for all patients to let them know exactly how it's going to go for them, but that's just not realistic.
[SPEAKER_05]: I just also want to touch on one other poignant question, Ms.
[SPEAKER_05]: Wise's daughter asked us Nick.
[SPEAKER_05]: She asked us what this diagnosis meant for her.
[SPEAKER_05]: After seeing a loved one suffering from dementia, I think it's only normal to wonder and worry if you're going to be next.
[SPEAKER_01]: So I would say a very common question or belief that patients and families have when they come in is, you know, that I got this because my family history is this, you know, my mother had Alzheimer's disease, I'm doomed, that's what I have it, there is that belief may be a strong word and, you know, my response depends on what information I have for the patient.
[SPEAKER_01]: So the easiest thing to say, which is almost always true, is age is the biggest risk factor, and that's what's driving your condition here.
[SPEAKER_01]: Most forms of dementia are not directly inherited.
[SPEAKER_01]: For Alzheimer's disease, for example, only 1% of cases have an optimal dominant mutation that causes it.
[SPEAKER_01]: I mean, there are a number of mutations, but altogether, they count folding about 1%.
[SPEAKER_05]: So to summarize, when telling a patient they have dementia, we need to find out what they know and what they want to know.
[SPEAKER_05]: We need to give them a clear message of what is going on, so they and their caregivers have an understanding of what to expect over time.
[SPEAKER_05]: The inevitable loss of ADLs, IADLs, and also how to prepare for those functional losses.
[SPEAKER_00]: Right, and when asked about risk to family, we can say, yes, mom has Alzheimer's, but it's very rarely genetic.
[SPEAKER_00]: So, okay, let's say that we have a patient and her family and they understand the disease.
[SPEAKER_00]: Now we're trying to talk about next steps, right?
[SPEAKER_00]: I mean, I know we said we don't have a perfect medication to fix this, but there are treatments for dementia, right?
[SPEAKER_05]: their sure are, and Ms.
[SPEAKER_05]: Wise's daughter had gone to Dr. Google and had seen some press releases about new medications that had been approved for Alzheimer's, and she came to us wanting to know more.
[SPEAKER_05]: She was really hoping they would be the right fit for her mom, but I knew I needed to know more before I could make any clear recommendations, and that leads us to deep dive to prescribing medications for cognitive decline.
[SPEAKER_05]: Nick, before we go too much further, I just want to point out that we are not talking about treatment for other dementia, like Parkinson's and vascular type today.
[SPEAKER_05]: We're just going to be talking about treatment for Alzheimer's disease, since that's what Ms.
[SPEAKER_05]: Wise had.
[SPEAKER_01]: So three of the medications are coal nesters, the inhibitors, the nephasal, the galantamine, and the risk technique, they're all approved for Alzheimer's disease at the stage of dementia, primarily mild to moderate dementia.
[SPEAKER_01]: The nephasal also at the stage of severe dementia.
[SPEAKER_01]: None of them are approved for mild cognitive impairment.
[SPEAKER_05]: So we have the nephasal, galantamine, and risk stigma in which are indicated for mild to moderate dementia, but not for mild cognitive impairment.
[SPEAKER_00]: Okay, so as a throwback to episode one, let me just remind myself, mild cognitive impairment describes patients who have some functional impairment, but are still able to do what they need to live independently.
[SPEAKER_00]: On the other hand, dementia or major neurocognitive disorder at any level is when patients have true dependence on others functionally.
[SPEAKER_05]: Exactly.
[SPEAKER_05]: Those are the folks who can't do everything for themselves.
[SPEAKER_00]: Okay, but like with that in mind isn't a kind of interesting that these medications aren't indicated from my old cognitive impairment.
[SPEAKER_00]: I mean, that seems counterintuitive, wouldn't we want to get them on medications and, you know, intervene ASAP?
[SPEAKER_01]: Patients certainly ask, you know, for treatment as soon as they can.
[SPEAKER_01]: But to say that it works better earlier is not based on data.
[SPEAKER_01]: So, I go with the data and there have been multiple trials at the stage of malcognitive parent with these drugs that I've not shown benefit.
[SPEAKER_05]: Yeah, I have to admit it was a bit disappointing to hear about and I agree it's counterintuitive, but you know, just because we want something to work earlier doesn't change the fact that the evidence isn't there, at least not right now.
[SPEAKER_00]: Okay, yeah, it's a fair point.
[SPEAKER_00]: Maybe earlier on, we're just really focusing on de-prescribing medications and optimizing the regiment.
[SPEAKER_00]: But, you know, we did see that Ms.
[SPEAKER_00]: Wise was having her ideals impacted, right?
[SPEAKER_00]: And she's starting to move beyond mild cognitive impairment into actual major neurocognitive disorder, dementia territory, right?
[SPEAKER_00]: So would she qualify for treatment with one of these medications?
[SPEAKER_05]: Yeah, Nick, you're right.
[SPEAKER_05]: She did qualify, but remember how this all started.
[SPEAKER_05]: She was already inconsistent with her anti-hypertensive regimen.
[SPEAKER_05]: And so, pill burden worries were real.
[SPEAKER_05]: And she hadn't come to us with any complaints of feeling unwell.
[SPEAKER_05]: So, after discussing this with her and her daughter, we recognized that we didn't want to make her potentially feel sick with a new medication, like one of the colonist race inhibitors at that moment.
[SPEAKER_01]: All three of these have, you know, the most common side effect is diarrhea, and so I always mention that first it could be 15 to 20% of patients develop diarrhea.
[SPEAKER_01]: There are other gastrointestinal side effects as well.
[SPEAKER_01]: And, you know, there are muscle aches, joint aches, vivid dreams, and so I go over the side effect profile, it's usually pretty well tolerated.
[SPEAKER_01]: rarely you can have breadycardia.
[SPEAKER_01]: There are really not significant side effects from this and you know, if you stop the medication, things result pretty quickly.
[SPEAKER_00]: Okay, so we're saying that these medications can have side effects and we should probably be really vigilant because, you know, population that's already vulnerable to falls, things like diarrhea, muscle aches, joint aches could definitely be a risk.
[SPEAKER_00]: But the wrist don't sound terrible.
[SPEAKER_00]: It really makes me wonder what are the benefits, what are the trade-offs that we're
[SPEAKER_01]: And almost all the trials were six month trials.
[SPEAKER_01]: And so you saw this improvement by three months, and then it's a war off by six months.
[SPEAKER_01]: So all the trials were one year, very few were longer than now.
[SPEAKER_01]: So I usually say you get maybe six or 12 months of modest improvement and then it wears off.
[SPEAKER_01]: Not slowing of decline, not stopping of symptoms.
[SPEAKER_01]: That's where you get a modest improvement and then they were off.
[SPEAKER_01]: That's how I, you know, phrase it in terms of what to expect.
[SPEAKER_01]: And it's not necessarily better at mild versus moderate dementia, you know, these drugs have been tested across that severity and it's not necessarily better earlier than later in that severity.
[SPEAKER_01]: And for Deneppe's uncleeting with severe dementia.
[SPEAKER_00]: I see patients on these medications for so long, so I think it's really good to repeat what we're saying here.
[SPEAKER_00]: For patients on these medications, we're expecting possibly six to 12 months of modest improvement, not slowing of the decline, not stopping of symptoms, potentially six to 12 months of modest improvement.
[SPEAKER_00]: With the potential risk for colder to excite effects, the we already discussed.
[SPEAKER_05]: And then there's Mammantine, which is an NMDA receptor antagonist, which is approved for moderate to severe Alzheimer's disease.
[SPEAKER_05]: And it really is well tolerated and tends to have more benefit on behavioral than cognitive symptoms without causing a lot of side effects.
[SPEAKER_05]: So clinically, if your patient is responding to Mamanteen as monotherapy, or in addition to colonist race inhibitors that we talked about, again, you're basically going to see some modest temporary improvement of symptoms for about six months.
[SPEAKER_00]: Yeah, and from what we heard, that means they might gain a point on their MMSC score, they make sure less irritability or agitation with Mantine, but after that, the decline can start again.
[SPEAKER_05]: gap.
[SPEAKER_05]: And Dr. Perry again made a good point when she was reviewing this episode that the brief symptom improvement with colonel stress inhibitors are more cognition-related versus with momentum, we're expecting more behavioral symptom improvement.
[SPEAKER_00]: got it.
[SPEAKER_00]: It's really good to finally clarify all that, but you know, we've talked a lot about adding these medications.
[SPEAKER_00]: Personally, my favorite pastime is actually getting rid of medications, especially ones we don't need, especially in patients who are older, who are cognitive issues.
[SPEAKER_00]: So, I guess when I see a patient in the hospital who's dementia's progressed, I'm looking at it in episode like, is that still worth continuing?
[SPEAKER_05]: You are always two steps ahead, Nick.
[SPEAKER_05]: I actually talked about this with our experts about when
[SPEAKER_01]: So I basically, you know, if past a year, we don't really see any more obvious benefit, I often will, you know, bring it up with patients and families.
[SPEAKER_01]: We can consider tapering the medication because why have another medication if it's not clearly helpful.
[SPEAKER_05]: So that's definitely one approach, but you know, another one of our consultants, Mary Beth, actually says that she often continues these medications for longer if the patient is tolerating them.
[SPEAKER_00]: Hmm.
[SPEAKER_00]: But why would we continue a medication if we're only expecting benefit for a short period of time?
[SPEAKER_05]: Well, some feel that there may be a potential benefit to moot or behavior.
[SPEAKER_05]: There was a meta-analysis that found that discontinuing colonist race inhibitors may have a negative effect on cognition and neuropsychiatric symptoms.
[SPEAKER_05]: But there are others who argue that the effect wasn't as clinically significant and the trials really weren't convincing to continue the medications.
[SPEAKER_00]: Sounds like we need to remember that these medications have not been shown to provide long-term stabilization for dementia, and we don't really have a lot of evidence of benefit after a year, so it's understandable that practice patterns start to diverge here on exactly how long to continue therapy.
[SPEAKER_05]: Yeah, there's going to be basically three scenarios where we're going to be talking to our patients about coming off of these medications one if the medications never really helped to if the medications are causing side effects and three if the medications did initially help, but it's been over six to 12 months and we're not really sure if they are still helping, but to be honest, Nick, it seems like there's going to be a lot of
[SPEAKER_05]: differing opinions between clinicians about if we decide to discontinue the medications immediately after a year or keep going for a little bit longer to avoid exacerbating any underlying neuropsychiatric or cognitive symptoms.
[SPEAKER_00]: Okay, so these are all the medications that I've heard of for dementia, but there's also a whole new class of medications for Alzheimer's disease, right?
[SPEAKER_00]: I don't know too much about them, but I assume they probably end in an ab and probably require
[SPEAKER_01]: These are anti-amiloid monocholante bodies.
[SPEAKER_01]: So we're very differently at a reduced amoloid plaque in the brain.
[SPEAKER_01]: And these are very specific for either a mild cognitive impairment or mild dementia due to Alzheimer's disease or evidence of amoloid pathology.
[SPEAKER_01]: So these are the first drugs that actually got approval for this stage of mild cognitive impairment.
[SPEAKER_01]: And certainly the first drugs that got approval to modify amoloid in the brain,
[SPEAKER_00]: Okay, wait, so I thought patients with mild cognitive impairment that they didn't have a lot of options.
[SPEAKER_00]: Is this some hope for these folks?
[SPEAKER_05]: Yeah, but it's a pretty narrow therapeutic window neck.
[SPEAKER_05]: So to be eligible for the anti amyloid monoclonal antibodies, like Lecanumab, a patient needs to be caught between mild cognitive impairment and mild dementia due to Alzheimer's disease.
[SPEAKER_00]: Okay, but can anyone with Alzheimer's disease and that window be a candidate for these meds?
[SPEAKER_05]: Well, we need to make sure that these medications are going to be effective.
[SPEAKER_05]: So our patients are going to need to have amoloid seen on their pet scan, and then they're going to need to be able to undergo MRI scanning.
[SPEAKER_05]: A couple of other contraindications to be aware of are things like the use of anticoagulants or immunosuppressants.
[SPEAKER_00]: Okay, so let's see you have a patient with Alzheimer's disease.
[SPEAKER_00]: They're between mild cognitive impairment and mild dementia.
[SPEAKER_00]: You know that they have amulet on their pet scan, and they don't have any other specific contraindications.
[SPEAKER_00]: So they're candidate for this medication, basically.
[SPEAKER_00]: What kind of benefit are we possibly talking about here?
[SPEAKER_01]: So the benefits on average of the trials that were 18 month long trials showed a slowing of decline.
[SPEAKER_01]: So now we're not seeing an improvement, but rather slowing and it's about a third of the pace slower for both drugs compared to placebo.
[SPEAKER_01]: And so that's also arguably modest, right?
[SPEAKER_01]: So it didn't stop the decline, certainly didn't cause an improvement.
[SPEAKER_01]: It slowed things down some.
[SPEAKER_01]: Most of the participants in the trials were on coal interest, inhibitor, and or memunting about 80% of them.
[SPEAKER_01]: So, in fact, this data is when it's an add-on, mostly an add-on to the standard drugs that have been out there.
[SPEAKER_01]: So, keep that in mind.
[SPEAKER_00]: Interesting.
[SPEAKER_00]: So obviously one takeaway here is that different medications for dementia can have different effects.
[SPEAKER_00]: You know, we said the colonest race inhibitors improved symptoms briefly, but didn't slow progression.
[SPEAKER_00]: On the other hand, here we have the antibody medications that don't improve symptoms, but they do slow progression.
[SPEAKER_05]: It's great to see benefit with treatment and the patient on mabs, but benefit is a little bit controversial.
[SPEAKER_05]: The slowing of decline was largely seen on cognitive and functional testing, it was statistically significant, but there are a lot of people who fail that the effect is nevertheless small and it's unclear how clinically significant the impact of these mabs is going to be.
[SPEAKER_00]: Hmm, I see, so, I mean, I can see these patients being interested in all the options when faced with the diagnosis like dementia, but if the benefit is incredibly substantial, I guess I'd want to know what the downsides are, too.
[SPEAKER_05]: Well, there is a pretty significant risk of infusion reaction with lecanum ab.
[SPEAKER_05]: Flu-like symptoms, headache, GI upset.
[SPEAKER_00]: Okay, I mean, not pleasant, but it doesn't sound like that's the end of the world, if it's just stirring infusions.
[SPEAKER_00]: I mean, could that be worth the trade-off for better brain function?
[SPEAKER_05]: Well, those reactions may be tolerable, but that's not the whole story.
[SPEAKER_05]: Have you heard of something called Aria?
[SPEAKER_00]: I don't think so.
[SPEAKER_00]: Sounds like what some new app is calling their AI companion.
[SPEAKER_05]: right or the latest oral contraceptive.
[SPEAKER_05]: It is actually a term to describe the side effects that can be caused by these amyloid monoclonal antibodies.
[SPEAKER_05]: ARIA followed by an E or an H. It stands for amyloid related imaging abnormalities with E for a Dima and H for hemorrhage.
[SPEAKER_00]: Oh, that does not sound good.
[SPEAKER_05]: No, really does not, but it is reversible swelling and the hemorrhages are micro hemorrhages if that makes you feel better, but if there are enough, they can become a macro hemorrhage.
[SPEAKER_01]: How frequent are these?
[SPEAKER_01]: So the micro hemorrhages about 10% of the adema for one of the drugs, it's a 12.5%.
[SPEAKER_01]: So these are not rare.
[SPEAKER_01]: It's rare to have them with symptoms and it's rare to have them with severe symptoms.
[SPEAKER_01]: So mild symptoms that are common are things like headache, blurry vision, or dizziness, and balance, but rare symptoms are things like seizures and stroke like symptoms or acute delirium.
[SPEAKER_00]: Wow, so 10 to 12% of our patients can have micro hemorrhages or a demon with a cannimab and denanimab.
[SPEAKER_00]: That is definitely a real risk, but in the other hand, it seems like the micro hemorrhages were asymptomatic and that has to be weighed against the potential benefit of giving these medications, a slowing of cognitive decline.
[SPEAKER_00]: That's really tough, and if it were my patient or my family member, I don't think I totally discount these medications, but how are we going to be able to give them safely?
[SPEAKER_05]: Yeah, so these require a lot of monitoring.
[SPEAKER_05]: The presence of a susceptibility gene called APOE increases the patient's risk for swelling and bleeding.
[SPEAKER_05]: So Dr. Marshall said it's standard of care to do genetic testing before starting treatment to better understand a patient's risk.
[SPEAKER_05]: And then there are the MRIs.
[SPEAKER_01]: And the first six months of treatment, we see the highest frequency of these side effects.
[SPEAKER_01]: And so we do for one of them before more MRI scans during our period.
[SPEAKER_01]: And we need to look for these potential abnormalities.
[SPEAKER_05]: So to just kind of keep this clear, a patient is going to get a pre-map MRI, and then we'll have four additional MRI scans in the first six months of treatment, because this is when area happens most commonly.
[SPEAKER_05]: And then if you find area, you're going to need to repeat the MRI monthly until the adema has resolved or the hemorrhages are stable.
[SPEAKER_05]: And then of course, you may need to obtain a PRN MRI if a patient is having symptoms suggest of a varia.
[SPEAKER_00]: That's a lot of MRIs.
[SPEAKER_00]: Okay, so then if you find a area is that a hard stop, like once you see the demon hemorrhages, sorry, no more medications.
[SPEAKER_01]: the guidance has been that if it's mild and there are no symptoms, you can continue dosing, but obtain repeated MRI scans monthly to make sure that it goes away with the deema, or that it's stable with the microhemerges because they don't really go away on the sequences that we measure, but we can see that they're not more of them where they don't evolve in size.
[SPEAKER_01]: However, if there are symptoms or it's moderate or severe in appearance, you will stop treatment until it goes away.
[SPEAKER_01]: If it's severe in appearance, we will not reintroduce it.
[SPEAKER_01]: But if it's not a severe, if it's mild or moderate, if it goes away, we can reintroduce it.
[SPEAKER_01]: And that's what was done in recent trials of these drugs and similar drugs.
[SPEAKER_05]: Yeah, I mean, like follow-up scans can tell you if chemo was working.
[SPEAKER_05]: It's kind of neat that we can see if the labs are working with imaging.
[SPEAKER_01]: And so a lot of places like ours now at 12 months were about 60% of the participants in the trials became amulet negative.
[SPEAKER_01]: We decided 12 months of treatment of the nanomap to repeat our pets can.
[SPEAKER_01]: And then if it's negative to say, okay, well, you don't need to continue treatment.
[SPEAKER_00]: Just to clarify, the end point of stopping treatment once amulet plaque is gone is based on clinical trials done on dinanamab specifically.
[SPEAKER_00]: This is really a field of ongoing study, especially in the cannab where we have even less
[SPEAKER_05]: Yeah, there's a lot of exciting research going on.
[SPEAKER_05]: So just to kind of summarize, if we see no more plaque at 12 months, we may just stop these antibodies because there is nothing more for the anti-ameloid medications to do because there is no more plaque.
[SPEAKER_05]: If patients have bad side effects, we may stop them, but unfortunately, it's also common to develop antibodies to denanimab at 12 to 18 months, which is yet another reason to stop the medication as obviously they are much less effective at that point anyway.
[SPEAKER_00]: So these medications sound appealing, but the benefit and mild cognitive impairment or mild dementia seems variable, and we need to really educate the patient on all the follow-up imaging and visits that are required to do this safely.
[SPEAKER_00]: That's a lot of MRI appointments and then a pet scan after a year.
[SPEAKER_05]: Yeah, this brings up an important point, Nick.
[SPEAKER_05]: The map journey is really going to look very different depending on where the patient lives.
[SPEAKER_05]: Access to subspecial care is so variable across the United States.
[SPEAKER_05]: Patients in rural areas are not going to have the same access to subspecialists and infusion centers as those in large cities with many academic medical centers.
[SPEAKER_00]: Yeah, and even though we found out that if patients are eligible, Medicare can cover quite a bit of these treatments, even if most of the treatment is covered, and even if that patient does live in a high resource setting, practically getting four MRIs scheduled and done and all the necessary fault appointments in six months, sounds just not easy.
[SPEAKER_05]: yeah, not easy at all.
[SPEAKER_05]: And just to remind us though, there is promise here, but these medications are new and it's uncertain how long lasting the positive impact is going to be.
[SPEAKER_05]: But Dr. Marshall is excited.
[SPEAKER_05]: There are newer drugs and development that will likely be better in tolerability, burden, and hopefully benefit.
[SPEAKER_00]: Well, I can't wait to see it.
[SPEAKER_00]: But we have covered a lot in the
[SPEAKER_05]: Okay, so just to summarize, we started talking about colonest race inhibitors, which we begin for mild to moderate dementia, and then can substitute with if there are side effects or add on mammalian for moderate to severe dementia.
[SPEAKER_05]: For colonest race inhibitors, we're looking for actual improvement in cognitive symptoms
[SPEAKER_05]: Both show benefit for about six to 12 months before the decline resumes, and side effects and colonist race inhibitors can be GI-related, joint pain, headache, and vivid dreams.
[SPEAKER_00]: And as for the monoclonal antibodies, these are for folks with mild-cardative impairment to mild Alzheimer's dementia.
[SPEAKER_00]: And we're looking to slow disease progression by actually clearing out amyloid plaque.
[SPEAKER_00]: The clinical significance of this benefit is still a little bit unclear, and that really does need to be weighed against the burden of monitoring and trying to prevent side effects.
[SPEAKER_00]: Infusion reactions can occur, but we really need to watch for signs of intercranial hemorrhage or edema with regular MRIs that areia side effect that we talked about.
[SPEAKER_00]: We stop the medications if these findings accumulate or if they cause significant symptoms, or if all the emerald plaque resolves on imaging.
[SPEAKER_05]: Awesome, so thanks for putting that all together
[SPEAKER_00]: and worries, but that reminds me that we talked a lot about medications for dementia, but most patients with dementia are on a lot of other medications too.
[SPEAKER_00]: Like, I often have patients with heart failure in dementia, and I'm sort of just like agonizing or what to do with their GDMT.
[SPEAKER_00]: Do I get more aggressive?
[SPEAKER_00]: Should I be deeper scribing?
[SPEAKER_00]: That's a lot.
[SPEAKER_05]: it totally is, but don't worry, that's what we get into in deep dive three.
[SPEAKER_05]: Patient-centered management for a patient with cognitive decline.
[SPEAKER_05]: As you said, we definitely don't want to harm our patients by removing essential medications, but you know, we've got to be realistic.
[SPEAKER_05]: Is the medication list in the chart the same as what is actually being taken at home?
[SPEAKER_04]: And so to go to the adherence question, let's start with that again, where on the spectrum is this person?
[SPEAKER_04]: If they're early on, they may still have the ability to adhere to a medlust, if we make the medlust simpler.
[SPEAKER_04]: If we take off any things that aren't that are having only a marginal benefit, maybe we're not going to have the gold standard of the heart failure regimen, maybe we're going to have the silver standard, maybe even the bronze or the tin, and we have to just be okay
[SPEAKER_04]: knowing that it's better to have them adhere to one pill than to not adhere to five pills.
[SPEAKER_05]: This is one of the really hard parts for me.
[SPEAKER_05]: There's this nagging feeling like I should be working towards getting someone on the perfect medication regimen, but I think we kind of forget sometimes what the reality looks like for our patients.
[SPEAKER_05]: Side effects, financial burden, or in keeping with
[SPEAKER_04]: again knowing what stage of disease they're at is going to dictate that if there are opportunities to change a medicine from the best option that's twice a day to a lesser option that's once a day absolutely do it.
[SPEAKER_04]: The other thing I think about in terms of deep prescribing is I start with the meds that have the highest likelihood for side effects and I use the word side effects constantly.
[SPEAKER_00]: Yeah, like, I mean, I don't know that I just start cutting all cardiac medications and a patient with cognitive issues, like some of these patients probably tolerate them just fine, but it sounds like once problems arise with adherents or side effects, you just need to look at each medication carefully.
[SPEAKER_00]: Like if one medication is hard to take, if the wrist is side effects are higher, or if you just don't think the benefit is going to seem as meaningful anymore, maybe it's time to question those medications.
[SPEAKER_00]: I know that I'm always looking at dioretics and beta-balkers pretty carefully in my patients' list to ask myself, do they still need these?
[SPEAKER_04]: You build a lot of trust with patients by starting things that are making them feel bad and by doing a lot of advertising and sales, pitch about what you think is going to improve, and then over time they may be willing to come off of more and more things.
[SPEAKER_00]: You know, that's such a good point of everything I do for a patient.
[SPEAKER_00]: Nothing makes them happier than when I say, hey, you actually don't need to take one of your medications anymore, especially if that was one that was giving them trouble.
[SPEAKER_05]: right.
[SPEAKER_05]: I mean, even the most elegant medication list is meaningless if our patient isn't following it.
[SPEAKER_05]: And, you know, we need to make sure our patients are taking their medications properly.
[SPEAKER_05]: But how we do this is probably going to change over time as their dementia progresses.
[SPEAKER_05]: At the beginning, all it may take is printing out an updated medication list for our patients.
[SPEAKER_00]: Yeah, that's a great first step.
[SPEAKER_00]: And then eventually over time, you may need to go to other
[SPEAKER_05]: Yeah, and Mary Beth reminded me that this doesn't have to be only the PCP's job to get medication sorted.
[SPEAKER_03]: Can we get somebody out there to see them?
[SPEAKER_03]: Can we refer to a home-based primary care?
[SPEAKER_03]: Somebody that can go into the home because I think you learn so much more and have so much more context.
[SPEAKER_03]: And often, occupational therapy, I find is really helpful at setting up practical strategies to help people as medicine management.
[SPEAKER_03]: What would work for them?
[SPEAKER_03]: Whether it's a pill box.
[SPEAKER_03]: I mean, there's so many more technologies of like time and auto dispensing pill boxes.
[SPEAKER_03]: So I think often they're really good at working with the person in their environment to find what will work.
[SPEAKER_00]: You know, I feel like so often we're just trying to get to this steady state with problems, right?
[SPEAKER_00]: Like we'd love for them to be on medications, they're doing well, we're just monitoring for issues.
[SPEAKER_00]: But most diseases don't work like that.
[SPEAKER_00]: They change over time, especially degenerate diseases like dementia.
[SPEAKER_00]: So we really just need to keep watching and adapting because there's not going to be a steady state.
[SPEAKER_05]: Exactly.
[SPEAKER_05]: And as the disease progresses, we need to keep coming back to those other factors that affect cognition that we discussed all the way back in deep dive one episode one.
[SPEAKER_00]: Right, that's a great point.
[SPEAKER_00]: I mean, some of the things we should be doing include consolidating any redundant medications, de-prescribing higher side effect medications, strategizing how we can optimize adherence to medications that they do really need, but also just continuing to check on sleep health, hearing, and screening for mood issues that could be contributing to these symptoms.
[SPEAKER_05]: And for general deep prescribing of medications, remember, focus on what patients are actually taking and create strategies to improve adherence, including having care team members actually go and investigate their home situation, and consider removing medications that are harder to take, have higher side effects, or those with diminishing returns.
[SPEAKER_00]: All right, so into what happened to your patient?
[SPEAKER_05]: Well, unfortunately it turned out she had pretty limited finances and really couldn't afford to expand her caregiver's hours very much, so we just basically try to get creative and looked for ways to get more people to check in on her.
[SPEAKER_05]: Her daughter was fortunately able to adjust her work schedule so that she could come and visit and check in more often and she called up some of the neighbors to help as well.
[SPEAKER_05]: Of course, we ordered home health.
[SPEAKER_00]: You know, as a hospitalist, I'm usually the one that gets involved when these best laid plans that you just talked about don't go as expected, like a patient submitted because they can't live at home anymore.
[SPEAKER_00]: The patients frustrated and the family so often feel like they saw this coming but just were powerless to stop it.
[SPEAKER_00]: I mean, it's really hard and really common.
[SPEAKER_05]: Yeah, I mean, dementia does often feel like a train we just can't stop, but you know what, Nick, the good news, we have the opportunity to really focus on what we PCPs love doing the best prevention.
[SPEAKER_05]: So here we go to deep dive for planning for an uncertain future.
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[SPEAKER_04]: The primary care of a person with dementia is largely preventive in terms of thinking about what is likely to go wrong in the next six to 12 months and what can I do about that?
[SPEAKER_04]: I think one of the things we keep emphasizing is having conversations that are looking ahead don't wait to have this conversation until the person needs that help.
[SPEAKER_04]: This is something I should be discussed as part of your advanced care planning early on.
[SPEAKER_04]: Shortly after the cognitive impairment has been identified,
[SPEAKER_04]: so that it's not a surprise when you've gotten to the point where it's necessary.
[SPEAKER_04]: And that's not the first time you're thinking about.
[SPEAKER_00]: And I think it's so important to say really explicitly that we're doing this because the time will come that mom can't make decisions for herself anymore or can't live alone.
[SPEAKER_00]: And we need to know who's going to make decisions at that time and what she would want those decisions to be.
[SPEAKER_00]: That's going to make it so much easier when that time does eventually come.
[SPEAKER_05]: Yeah, and remember, we don't have to be a lone wolf in all of this.
[SPEAKER_05]: We should look out for other professionals who can help us.
[SPEAKER_03]: I'm immediately thinking of who else can help me.
[SPEAKER_03]: Between visits, so really leaning on my case management and social work colleagues to start getting to know the patient, talking about and exploring community resources, are they eligible for any additional in-home assistance?
[SPEAKER_03]: I think that I really start to think about who can help me on my team when it gets to be
[SPEAKER_00]: Okay, so basically, we know this person's going to need more and more help, so we want to see what's available and mobilize the troops early before it becomes an emergency.
[SPEAKER_05]: Yeah, there's this really uncomfortable goldie lock zone with dementia where patients still have the capacity to elect a live alone, but they're really having more difficulty and family and providers are increasingly worried about their safety.
[SPEAKER_00]: Yeah, I mean, we can't force these folks to stop living alone, but having a safety net or a backup plan in place made up of services, informed family and friends, neighbors, regular check in with providers is huge.
[SPEAKER_00]: I mean, I've seen it be the thing that gets patients help when someone in this network sees something as wrong before it turns into an avoidable emergency.
[SPEAKER_03]: there's what we as clinicians think needs to happen and then there's what the patient is willing to do and so I think just keeping that in mind and another other question that I find really helpful when you're thinking about the need for more care is how will you know when the planet home isn't working anymore or what's kind of your line in the sand where
[SPEAKER_03]: you feel like you can do it, and a lot of times that may be like in continents.
[SPEAKER_03]: So like when moms in continent, I'm not going to be able to do it anymore.
[SPEAKER_03]: But knowing that ahead of time, I think really helps them, especially when you're assessing their functional status and the stage.
[SPEAKER_03]: As you're nearing that, you can be talking about this more and kind of planning.
[SPEAKER_00]: Patients often say they want to live alone even as dementia progresses, but I've never thought to ask them when would they no longer feel safe living alone, or, you know, what quality of life would be acceptable living alone?
[SPEAKER_00]: That would make it a lot easier to know when the time has come to transition to new living situation, like really start that conversation.
[SPEAKER_05]: Yeah, can you imagine how helpful that would be for their family for clinicians if they ever aren't able to communicate their own wishes to us?
[SPEAKER_00]: Yeah, exactly.
[SPEAKER_00]: I mean, these situations always stress me out.
[SPEAKER_00]: I mean, like, take COPD, for example.
[SPEAKER_00]: It can definitely be dangerous, but at least someone with worsening short is subrath usually reaches out for help.
[SPEAKER_00]: I'm not usually sitting and wondering on my COPD patients who're doing it home, but dementia can be quietly worsening.
[SPEAKER_00]: We really need alarm bells, eyes on the patient.
[SPEAKER_00]: You know, layers of support to be our warning, are canary in the coal mine.
[SPEAKER_05]: It's uniquely worrisome territory for clinicians, isn't it?
[SPEAKER_05]: I mean, who is going to sound the alarm?
[SPEAKER_05]: Who is going to be the bad guy and tell a patient they should move to a facility or stop driving?
[SPEAKER_05]: This really can be so touchy.
[SPEAKER_03]: I think these are always hard conversations, and again, we take on a lot of the burden as the PCP and feel like we need to make the most perfect situation.
[SPEAKER_00]: And sometimes I also worry like,
[SPEAKER_00]: am I to blame if I discharge a patient home alone because they refuse the nursing facility that we recommended.
[SPEAKER_00]: They fall and break a hip and aren't found for a day or two.
[SPEAKER_00]: I mean, are we at fault?
[SPEAKER_05]: Yeah, you're not alone in that worry.
[SPEAKER_05]: I feel that sense of dread to.
[SPEAKER_05]: I wonder if it's my legal responsibility to get a driver's license taken away.
[SPEAKER_05]: I think we really do worry so much about patient safety.
[SPEAKER_04]: I think we often find that we're in this role where we feel like we have to act almost in local parentheses as though we're responsible for our patient's lives.
[SPEAKER_04]: We are not responsible for our patient's lives.
[SPEAKER_04]: And practically, we're not going to be held responsible for people making bad decisions, even if they have impaired brains, which is what dementia's ultimately are, is brain damage.
[SPEAKER_04]: The driving question I think could be the subject of its own episode of a podcast because it's really complex and really fraught.
[SPEAKER_04]: And the first thing I want to say about that is probably the most common issue where a patient's likely to fire their PCP is over a conflict about driving.
[SPEAKER_04]: So the hack that I did when I was in primary care is I had an agreement with my practice partner.
[SPEAKER_04]: where I would see all of his patients to have the driving conversation and he would see all of mine so that we could be the bad guy who the patient came back to say, can you believe that other jerk of a doctor reported me to the DMV and allowed that PCP patient relationship to remain intact?
[SPEAKER_00]: Sounds like the geriatric inversion of good cop bad cop.
[SPEAKER_05]: Yeah.
[SPEAKER_05]: The key, though, once again, as Dr. Perry and Mary Beth have already stated, plan ahead, have these conversations before a car accident happens.
[SPEAKER_05]: Outline early on, what's going to be that proverbial straw that breaks the camel's back that will make someone voluntarily give up their license and fight a caregiver into their home or move into an assisted living or memory care facility.
[SPEAKER_00]: I feel like I've learned so much today and do, so let's summarize a little bit.
[SPEAKER_00]: In deep dive one, we talked about breaking the news of cognitive impairment, how we should find out what our patients understand and what they're ready to hear, so we know how to deliver that news.
[SPEAKER_00]: But, we should still be very clear about the nature and prognosis of the disease, including that everyone's trajectory is going to look different as going to be hard to predict.
[SPEAKER_05]: And in deep dive too, we talked about how colonest race inhibitors can provide an actual period of improvement in cognitive symptoms and mamentine in behavioral symptoms.
[SPEAKER_05]: But this isn't contrast to the monoclonal antibodies which actually work to slow the worsening of cognitive decline, but the clinical significance of this is still somewhat controversial.
[SPEAKER_00]: And remember that the monoclonal antibodies are approved from mild cognitive impairment in mild dementia, the colonestrates inhibitors are approved in mild to moderate dementia, and Mamanteen is approved in moderate to severe dementia.
[SPEAKER_05]: And we also have to monitor for side effects.
[SPEAKER_05]: With colonest race inhibitors, this can include GI symptoms, muscle pain, joint aches, and the monoclonal antibodies can cause infusion reactions and need regular MRIs to evaluate for edema and micro hemorrhages.
[SPEAKER_00]: And in deep dive three, we talked about deep prescribing medications, focusing in those with more side effects that are hard to take, or it may not have as much long to do no benefit.
[SPEAKER_00]: And ultimately, the best medication list is the one that your patient takes.
[SPEAKER_00]: So strategize what will realistically help them take their medications at home.
[SPEAKER_05]: Well said, Nick, and a call out back to episode one, make sure to screen your patients for sleep disturbances, depression, and hearing loss as they all can have a large impact on brain health.
[SPEAKER_05]: And you are so great at concisely summarizing key points, but I hope you're okay if I let our experts wrap it up with some key takeaways from deep dive for.
[SPEAKER_00]: Of course, take it away.
[SPEAKER_04]: One is that this really is a longitudinal disease.
[SPEAKER_04]: And you can't treat the patient well if you're not looking at where are they now?
[SPEAKER_04]: Where are they going to be by following them very regularly assessing where they're at and thinking ahead, giving them that information in the bite-sized pieces.
[SPEAKER_04]: Point number two, always doing that resources and counseling in the bite size pieces that they can handle.
[SPEAKER_04]: I also think of advanced care planning as kind of like this.
[SPEAKER_04]: In some ways, I think of advanced care planning as a longitudinal process where I'm doing bit by bit at different points depending on their sort of current emotional state of being.
[SPEAKER_04]: Point number three that we really want to take home is that when you're taking care of a person with dementia, you really have two people that you're responsible for.
[SPEAKER_04]: Your patient, but also their primary caregiver.
[SPEAKER_03]: Our overarching goal is to improve the quality of life for the person with dementia and their caregiver.
[SPEAKER_03]: And I think just reinforcing the relationship with the caregiver is so critical, they can be your best teammate in this.
[SPEAKER_03]: And so, you know, I think we want to talk to the caregiver and often the caregivers the one that has the
[SPEAKER_03]: accurate history that we're wanting, but I think one thing I always like to practice is that I'm going to talk to the person with dementia first.
[SPEAKER_03]: In all my visits, I'm going to sit and face them.
[SPEAKER_03]: I'm going to ask them questions.
[SPEAKER_03]: They may not give me all of the accurate history, but I want to keep that rapport with my patient and honor them.
[SPEAKER_05]: Wow, it has been a journey, I guess really apps since we're talking about a disease that requires longitudinal connections and therapeutic relationships between patients, caregivers and clinicians.
[SPEAKER_05]: I hope we've helped demystify cognitive disorders just a bit with this episode and the last one.
[SPEAKER_05]: It's been such a privilege being here with you discussing this really important topic.
[SPEAKER_00]: Thanks to you and do for putting together a great series of episodes.
[SPEAKER_00]: I know we all learned a lot and I'm definitely going to have to listen to this one again.
[SPEAKER_00]: And thanks to our discussions and the audience for being here in listening.
[SPEAKER_00]: You can all find our show notes, graphics, and more at Coreiampodcast.com.