Previous Next

Time Stamps

• Cognitive Concerns During a Routine Follow-Up
• Deep Dive 1: How do you pivot when you recognize unexpected memory issues?
• Deep Dive 2: What tools should we use to characterize and stage cognitive decline?
•  Deep Dive 3: How do we determine the etiology of cognitive decline?

Sponsor: DoxGPT

Check out DoxGPT by Doximity and see how it can simplify your clinical workflow, from patient care to paperwork. Visit: https://www.coreimpodcast.com/DoxGPT 

Show Notes

Deep Dive 1: Recognizing and Responding to Cognitive Concerns

• Cognitive issues take priority: These issues may impact patients’ ability to adhere to medical plans, if suspected, cognitive issues should be addressed before other (non-emergent) medical plans
• Workup is a process: Diagnosis typically requires 3–4 visits; break it into manageable steps:
  • First step: Screen for cognitive issues or mimics/contributors to cognitive impairment
  • Second step: Perform formal cognitive testing
  • Third step: If cognitive impairment is confirmed, perform further testing to determine etiology
  • At each visit, consider how to move care forward
    • Set inter-visit tasks: 
      • Gather collateral information, order indicated labs/imaging, and appropriate specialty referrals
    • Ask who else can help?: Home health, social work, PT/OT, family, neighbors
    • Plan for the future: What can go wrong? Is a safety net in place?
• How to screen for cognitive decline:
  • Use direct but less charged language: 
    • “How’s your brain?” 
    • Instead of “How’s your memory?”
  • Ask about sleep: “Sleep is nature’s best medicine for the brain.”
    • Sleep disorders (e.g., apnea, REM behavior disorder) can affect cognition.
  • Review medications: 
    • Screen for anticholinergic medications (e.g., diphenhydramine in Tylenol PM, oxybutynin)
    • beta blockers
    • Centrally acting medications like benzodiazepines
    • Antipsychotics 
  • Check for hearing loss:
    • Early intervention with hearing aids can reverse decline.
  • Screen for depression: 
    • PHQ-2 or PHQ-9
    • Pseudodementia can mimic cognitive impairment.
• Collaborative history: 
  • Seek out collateral from family, loved ones. 
  • If the family disagrees with a patient’s self-assessment, respectfully include their perspective.

Deep Dive 2: Characterizing and Staging Cognitive Decline

• Mini-Cog:
  • Quick screening tool (3-word recall + clock draw).
  • Positive result → schedule dedicated cognitive visit (see testing tools below)
  • Clinical intuition matters. 
    • A normal Mini-Cog result does not rule out cognitive issues in someone with high pretest probability or a prior diagnosis
• Spectrum of cognitive changes:
  • Subjective Cognitive Decline: Patient notices changes
    • Testing is normal. 
    • Can occur with normal aging.
  • Mild Cognitive Impairment (MCI):
    • Objective deficits on testing (not just normal aging)
    • Daily function and independence is largely preserved.
  • Major Neurocognitive Disorder (formerly “dementia”):
    • Cognitive deficits on testing and clinical assessment.
    • Daily life functionally impacted (e.g., medication management, driving, ADLs).
    • Stages: mild, moderate, severe, reflecting progressing functional dependence
• Progression is variable: 
  • The rate of decline depends on many factors, such as age, baseline cognition, comorbidities, and lifestyle factors.
• Testing tools for cognitive staging
  • MoCA vs MMSE:
    • MoCA is more sensitive for early disease (89% sensitivity for MCI).
    • MMSE widely used but less sensitive for mild impairment.
    • Generally helpful to pick one test and track this over time
  • Alternative tools: 
    • SLUMS and RUDAS for cultural and educational inclusivity.
  • Tests available in multiple languages
    • Professional medical in-person interpreters preferred. 
    • Video interpreters are better than a telephone alone.
  • Limitations of cognitive tests:
    • May be biased by education/culture.
    • Do not fully capture functional ability.
• Testing tools for functional staging:
  • The progression of functional decline often mirrors early childhood developmental milestones in reverse 
  • FAST Scale (Functional Assessment Staging Tool): 
    • Stages 1–7 based on what the patient can do 
    • E.g., independent vs loss of ability to smile, talk, walk
  • Descriptive review of what ADLs an iADLs a patient can or can’t do
    • Activities of daily living (ADLs): 
      • Activities to care for yourself (bathing, dressing, eating, toileting, transferring).
    • Instrumental activities of daily living (iADLs): 
      • Activities to care for your life (medications, finances, meals, housekeeping, driving).
• Document cognitive and functional staging regularly to track over time
  • Document the stage of cognitive impairment as specifically as possible: 
    • MCI, mild/moderate/severe dementia
  • Document functional status clearly in clinic notes, inpatient progress notes, discharge summaries
    • Can use FAST scale or descriptive review of ADLs/iADLs as above
    • Include living situation, cognitive stage, and functional abilities in a one-liner 
    • Ex: 77yo living alone, MoCA 24/30, FAST 4, independent in ADLs but needs help with meds and finances
  • Functional changes guide care planning and safety interventions.
  • In advanced dementia, functional description often becomes more important than cognitive scores.

Deep Dive 3: Determining Etiology of Cognitive Decline

• Why identify etiology?
  • Guides treatment 
    • E.g., Alzheimer’s disease has disease-modifying options.
  • Helps with prognosis and planning for future care
  • Note: Determining precise etiology may be less impactful in severe cognitive impairment given treatment options limit and prognosis already poor
• Rule out reversible causes as above: 
  • poor sleep, offending meds, hearing loss, psychiatric issues like depression
• Assess for metabolic factors: TSH, B12, treponemal testing, HIV.
  • Note that positive treponemal testing should include a review of whether the patient has previously received treatment
• Look for patterns of presentation of non-Alzheimers Dementia:
  • Lewy Body Dementia: Hallucinations, sleep disturbances, Parkinsonism.
  • Frontotemporal Dementia: Early behavioral changes, disinhibition.
  • Vascular Dementia: Associated with prior strokes or infarcts on imaging.
  • Atypical presentations:
    • Remember that other disease processes can present with symptoms also seen in dementia: brain tumors, seizures, encephalitis, stroke, pseudodementia due to major depressive disorder.
• Obtain Imaging: MRI (preferred), CT if MRI not feasible.
  • MRI can show specific findings in different forms of dementia
    • Alzheimer’s Dementia and Lewy Body Dementia: Both show diffuse atrophy, however medial temporal and hippocampal volume is spared in Lewy Body Dementia and diminished in Alzheimer’s dementia
    • Frontotemporal Dementia: Frontal and temporal atrophy
    • Vascular Dementia: Prior infarcts and ischemia
  • Usually covered by Medicare if clinically indicated.
  • PCPs can order imaging and labs; specialist referral is not always required.
  • Check with your local institution regarding the name of the MRI protocol done for cognitive deficit diagnosis.
• Specialist role:
  • Neuropsychological testing for complex cases.
  • Advanced biomarkers (e.g., Amyloid PET) for Alzheimer’s confirmation and eligibility for new monoclonal antibody treatments (Lecanemab, Donanemab).
• Empowerment for PCPs:
  • Start with clinical evaluation, cognitive testing, labs, and MRI.
  • Refer when presentation is atypical or advanced diagnostics are needed.

Transcript

Dr. Nick Villano: The following is meant to be for medical education and not formal medical advice. Remember to always consider the patient in front of you, especially with matters as gray as these. The views expressed in this episode don’t reflect the views of any affiliated institutions.

Dr. Laura Perry: I think a lot of folks really shy away from addressing cognitive impairment because it often feels so hopeless, because many of these diagnoses are really devastating and don’t have the greatest treatments, but you’re really doing everyone a disservice and propelling the patient towards a crisis point when there’s a lot that can be done to prevent that crisis.

Dr. Nick Villano: Welcome to Gray Matters, where we unpack how medical management is rarely black or white

Dr. Indu Partha: And go on lots of deep dives along the way.

Dr. Nick Villano: I’m Dr. Nick Villano, and today I’m joined by a new friend.

Dr. Indu Partha: Hey Nick. Hey everyone. I’m Dr. Indu Partha, a general internist and PCP at the University of Arizona College of Medicine, Tucson, and Banner University Medicine.

Dr. Nick Villano: Alright, Indu, it’s great to be here with you.

Dr. Indu Partha: I am so excited to be joining you today, Nick. This is my first CORE IM podcast, and I honestly just can’t believe it. I have been a long-time listener and now a first-time host.

Dr. Nick Villano: Yeah, super exciting. And that opening sound bite definitely hit pretty hard for me. Sounds like you’re bringing a pretty tough case to us today.

Dr. Indu Partha: Yeah, tough but common and important. We took care of a patient in resident clinic a while ago whose routine follow-up turned into a pivot and redirect. But honestly, Nick, I think many of our listeners are going to relate to this story.

Dr. Nick Villano: Okay, I’m definitely hooked. Tell me more.

Dr. Indu Partha: So, let me introduce you to Ms. Wise, Nick. She was a 77-year-old woman. We were following regularly in our internal medicine residency continuity clinic for hypertension, which had been well controlled until one day it just suddenly wasn’t the resident and I were caught off guard. Ms. Wise was consistent, and we knew her well, but now she was very confused about what her home medications and blood pressures were, and she hadn’t done any of the nursing follow-up that we had suggested at our last visit.

Dr. Nick Villano: That seems really jarring. I mean, you said you knew this patient really well, knew sort of their adherence and how they had been pretty regular about following up. What do you think changed for them?

Dr. Indu Partha: Yeah, we were caught off guard and just equally confused. It just wasn’t our blood pressure. It was sort of like the visit started going sideways. I mean, we were repeating the same instructions we had given on our last visit, and I was just wondering if perhaps we hadn’t been clear enough or our plan was too complicated. We tried to keep asking her different types of questions, but her answers kept going off topic and didn’t really make sense, and then it hit me. I was wondering maybe this was an issue with her mind. Did she have a cognitive deficit we hadn’t picked up on?

Dr. Nick Villano: Oh man. So you’re trying to work through her blood pressure, and now you start worrying about her memory. That is a can of worms, and to be honest, I really don’t know where to start with it. I mean, what do you do now? Do you stick to your original plan, go through her chronic medical issues, or do you really have to get into the memory issues now?

Dr. Indu Partha: Yeah, I mean, we were getting a bit anxious and overwhelmed to do we need to make this into a memory visit or could we just wait until her annual wellness exam? I mean, I know that this is a scenario that happens to a lot of us, and I knew I needed some help, so it was great to sit down with some wonderful geriatricians to make this all just a bit more manageable. So let’s head to our first deep dive. How do you pivot when you recognize unexpected memory issues?

Deep Dive 1:  How do you pivot when you recognize unexpected memory issues?

Dr. Laura Perry: I think when you start to have the suspicion, is when it becomes the primary issue that you have to manage, and everything else has to take a backseat. It doesn’t matter to me if you’re concerned that this person may have an active malignancy and needs a workup. If you have not addressed the elephant in the room, that their brain may not be functioning the way it used to, they will not be able to follow up on whatever beautiful plan you create to work up that other issue. And you have to identify one, what is going on, two, what the severity is, and three, what resources they have in place, and four, what resources they need to be able to manage their health going forward. So it takes primacy.

Dr. Indu Partha: That is Dr. Laura Perry who we also heard at the top of the episode.

Dr. Laura Perry: My name’s Laura Perry. I am the Springs Living regional chair of geriatric medical education for Providence in Oregon.

Dr. Indu Partha: So I mean, I get what Dr. Perry is saying. We usually have an agenda for a visit, and then when something new and not easy to tackle, like cognitive impairment, comes up, it can be really tempting just to push it off to the next visit. But Nick, right now, we needed to acknowledge that cognitive impairment was Ms. Wise’s most critical problem.

Dr. Nick Villano: And I mean, even if it’s not easy to tackle and takes time, I mean, you could argue that’s even more reason to get the ball rolling.

Dr. Laura Perry: To work up cognitive impairment, come up with a diagnosis, and a plan is going to tak,e on averag,e about three to four visits. And I like to divide that process up into what am I going to accomplish this time? What do I need to do in the intervisit care? How can my clinic team support me in getting those things done? And then how can I plan for a successful next visit?

Dr. Indu Partha: So I felt a lot better hearing this. We need to address the elephant in the room, but hey, we don’t need to figure it all out now. It may take up to three or four visits,

Dr. Nick Villano: So we’re just getting started, and we can take this in pieces. That’s definitely reassuring, but we’re definitely going to need to start somewhere, right, asking the patient some questions. I mean, that’s why I think this feels hard to me. How do you ask someone questions about their memory without them feeling defensive at best and maybe even insulted at worst?

Dr. Laura Perry: Asking about cognitive health as part of my general review of systems, and I have two questions that I do as part of that. One, I ask, how’s your brain? I think that that is a less charged way of asking rather than saying, how’s your memory? Because neurodegenerative dementias don’t just incorporate memory. They also can include things like organization, executive function, mood.

Dr. Nick Villano: How’s your brain, really? I was imagining something a little less, I don’t know, very direct. I mean, does that work?

Dr. Indu Partha: Yeah, believe it or not, it gets some pretty straightforward responses  like I just don’t think I’m as sharp as I used to be.

Dr. Nick Villano: Yeah, I mean I get that. I think if the patient has some insight that can be super helpful, but we see for a lot of issues. I could also imagine the patient saying, “I’m fine!”

Dr. Indu Partha: But then we see the adult child or the spouse vigorously shaking their head in disagreement in the background basically saying, “No, they are not fine”.

Dr. Nick Villano: Yeah, I’ve definitely seen that before. I mean, these stories never just have one side.

Dr. Indu Partha: Yeah, they never do. But Dr. Perry offered a really good piece of advice where she said she just redirects the conversation, saying something like, “I see your daughter disagrees. Do you mind if I get her perspective on what’s going on?”

Dr. Nick Villano: I like that. That’s kind of a respectful way of getting a collaborative history. You’re not dismissing the patient, you’re including the family.

Dr. Laura Perry: The other question that I ask about is how is your sleep? Because there’s so many other factors that can lead to cognitive impairment. Often, the best sort of gateway into that conversation is talking about sleep, which is such a problem for so many people. And what I will tell people is sleep is nature’s best medicine for the brain. If you’re having trouble sleeping, of course, you’re not going to feel your smartest or your sharpest.

Dr. Nick Villano: I would love it if all of our podcasts just end up being an advertisement for sleep. I mean, who doesn’t love sleep? But to be serious, asking about sleep is going to help us in a few ways. I mean, sleep apnea is super common, and it’s been associated with a higher risk of dementia. Even if the evidence of how treating it affects dementia risk is not super clear yet. Also, sleep arousal issues like acting out dreams while sleep or restless leg syndrome can be seen in a specific type of dementia, Lewy body dementia.

Dr. Indu Partha: So it seems pretty clear that we need to ask about brain and sleep health to get a quick snapshot into our patient’s cognitive health, but we’ve got to keep in mind that there are other things that can impact our patient’s brains and though there are lots of things we could be highlighting, I think three super common and low hanging fruit that we can address today are medications, hearing and depression.

NP Mary Beth Kuebrich: I think I really like to specifically ask, do you take any over-the-counter medicines? And I might even specifically say, do you take anything for sleep? Do you take Tylenol PM? Because I think people just don’t think about it. And sometimes if they bring all their bag of medicines in and you find enough anticholinergic medicines, there’s a lot of potential to improve their cognition. 

Dr. Indu Partha: That’s Nurse Practitioner Mary Beth Kuebrich, our next discussant. 

NP Mary Beth Kuebrich: I’m Mary Beth Kuebrich. I’m a nurse practitioner at Providence Health in Portland, Oregon. I also help lead our dimension navigation service, which aims to better support caregivers of people with dementia.

Dr. Nick Villano: So talking about medications reminds me of when we were initially workshopping this episode, A friend of the pod, Dr. Emily Cetrone, told us about a patient who was taking nightly Benadryl to sleep. Emily stopped it, and basically, her signs of cognitive decline completely cleared. I mean, that was super notable to me, the effect a medication can have. And it’s also surprising how many of these PM medications have diphenhydramine or another first-generation antihistamine in them?

Dr. Indu Partha: Yeah, you’re reminding us of what we should always be doing, a thorough prescription and over-the-counter medication reconciliation. I mean, we had a patient who complained to us that she was just feeling so foggy-headed every single day. We ended up stopping her oxybutynin, and boy, what a difference. She was so grateful to us for making her feel so much better. Another quick and easy thing to do, Nick, check your patient’s hearing.

Dr. Laura Perry: There’s an increasing wealth of literature that’s come out over the last five or 10 years showing that we have this window of opportunity with hearing loss, that there’s a very strong two-way relationship between hearing loss and how our brain functions. And if you catch someone in this window of opportunity and get them hearing aids that they use consistently, you can actually reverse cognitive decline. But if you wait too long and the brain goes without that input that it needs to function properly, eventually you’ll have irreversible neurodegenerative disease.

Dr. Indu Partha: Another thing we just should not forget to do is to screen for depression. A person’s mental health has a tremendous effect on the brain and cognition, and this phenomenon is called pseudodementia. So we need to make sure we screen all our patients with tools like the PHQ-2 or the PHQ-9, and this will really help us figure out if our patient needs referral to mental health services or a referral for dementia care.

Dr. Nick Villano: That’s such a great point, but just to reorient us, we’ve looked at our patients’ sleep, we’ve looked at their med lists, we’ve assessed them for hearing loss and depression. Let’s say we’ve done all that and maybe we found some things, but we’re still worried something else is going on. I feel like we need to back up that worry about some kind of cognitive impairment with something a little more objective, measuring their memory in some way.

Dr. Indu Partha: Yeah, I mean, I think we all do much better with numbers and certainties, so we definitely need to find something objective to document our patients’ cognitive decline.

Dr. Gad Marshall: So the mini-cog takes probably two or three minutes to do. It’s basically a three-word recall and a clock drawing task. It can tell you if there is something suspicious here for either dementia, if it’s overt, or at least some degree of cognitive impairment.

Dr. Indu Partha: That’s Dr. Gad Marshall, our third and final discussant.

Dr. Gad Marshall: I’m Gad Marshall. I’m a behavioral neurologist in Boston, and I’m the director of clinical trials at Epicenter for Alzheimer research and treatment at Brigham.

Dr. Nick Villano: Okay. I’m on board with the mini-cog. I mean, it sounds like it’s short, it’s easy to add on, and can be administered by clinic staff, but if this is a screening test, I’m guessing if the mini cog is positive, we still need to do more detailed testing to confirm it. Right?

Dr. Indu Partha: Let’s not forget that our clinical concern is a screening tool too, Nick. If a patient shows signs of cognitive decline or has a diagnosis already, we really shouldn’t be reassured that the Mini-Cog is normal. We need to follow up on our clinical intuition, and once the issue is found, we really do need to bring our patient back for a formal focus on memory loss, and we’re going to review details on how we did that with Ms. Wise in Deep Dive 2.

Dr. Nick Villano: Got it. So maybe I could take a stab at summarizing this deep dive. Basically, if something makes us worried about our patients’ cognitive health, we should start by just asking them directly about their brain health. Then we should ask them about their sleep health, dive into any sleep habits to make sure they’re doing a good job there, and look out for nocturnal symptoms. Then we should screen their medication list, including over-the-counter medications for anything that can affect cognition, especially anticholinergics, not forgetting that a lot of sleep aids like Tylenol PM and Benadryl have these anticholinergic effects. The last two things make sure that you test your patient’s hearing and you screen them for depression.

Dr. Indu Partha: Fantastic. I think we’ve got our listeners up to speed, and we’re going to head back to Ms. Wise. So she was not on any concerning medications, and her hearing was fortunately fine, but as far as her mini-cog was concerned, there were problems. She only had one word recall, but the clock draw was fine. So my resident and I were really glad that we had paid attention to that initial instinct that something was wrong with her memory. But if I’m being honest, we now sort of felt like we had opened up Pandora’s box. Basically, we were at that, “Now what do we do moment?”

Dr. Nick Villano: Yeah, I totally empathize with that, and I agree. I’m convinced something’s going on with your patient, too. But I don’t really know where we go from here. I mean, are we testing for dementia now? Is this whatever the heck mild cognitive impairment is?

Dr. Indu Partha: Yeah, I think a lot of us wonder how we’re supposed to quantify or qualify something that has been traditionally such a clinical diagnosis. We don’t have a biopsy, we don’t have an echo that can help us stage or grade our patient’s symptoms. This led me to our second deep dive. What tools should we use to characterize and stage cognitive decline?

Deep Dive 2:  What tools should we use to characterize and stage cognitive decline?

Dr. Laura Perry: One of the most common errors that we see in caring for someone with dementia is that people assume that dementia is like an on-off switch. You either have it, or you don’t, but it is a progressive disease, and the most important part of caring for someone with dementia is figuring out where on that spectrum are they that’s going to determine everything about how you care for them.

Dr. Indu Partha: Nick, let’s talk about one end of the spectrum. Have you ever had a patient or a friend come and talk to you with worries about their memory, but then, when you ask some more questions, you realize that their day-to-day life really isn’t being affected?

Dr. Nick Villano: Oh yeah, definitely. They forgot why they went into a room, or maybe they can’t remember the name of an actor in a TV show. They used to know, but generally they seem fine. I can’t remember actors’ names either.

Dr. Indu Partha: Yeah, I think this is really common, and it happens to the best of us, and when we do the testing, the mini-cog is normal. This is what we call subjective cognitive decline.

Dr. Nick Villano: Okay, so subjective cognitive decline is that family member who’s worried about their memory, but there isn’t any clear pathology, at least not yet. And this can definitely be a part of just normal aging. I’d imagine if that’s subjective cognitive decline, there must be an objective cognitive decline, right?

Dr. Indu Partha: There is, and I really hope our listeners by the end of this podcast understand how to properly classify objective cognitive decline. So someone with mild cognitive impairment or MCI is going to have some objective changes, like a lower score on a cognitive test, and their daily function is generally preserved, but others in their lives may have noticed some changes like forgetting recent conversations.

Dr. Nick Villano: So, mild cognitive impairment sounds like there’s more cognitive impairment than subjective cognitive decline. That makes sense. And it sounds like there’s maybe some functional issues, but nothing too severe, that sounds a little bit clearer to me now. And then is the stage after that if someone progresses dementia?

Dr. Indu Partha: Yes. So I learned that the DSM-5 has replaced the term dementia with major neurocognitive disorder in an effort to kind of reduce the stigma that’s associated with the word and to better reflect the spectrum of severity. So a person who is diagnosed with major neurocognitive disorder will have deficits both on their clinical assessments and their objective cognitive testing. And these are folks whose daily lives are actually impacted in a way that others have noticed; they might not be able to manage their medications, or they may get lost while they’re driving. These are the folks, Nick, that are going to maybe need assistance with dressing or toileting.

Dr. Nick Villano: So if I was to lay out the spectrum of objective cognitive decline, it would start with mild cognitive impairment, and then it would progress to major neurocognitive disorder, and then within major neurocognitive disorder or dementia, you would have mild, moderate, and severe disease.

Dr. Indu Partha: Yes, that’s exactly right. And if nothing else, I hope our listeners come away with a really clear understanding of these various buckets in describing their patients’ cognition.

Dr. Nick Villano: It can definitely be confusing. I mean, we have disorders, declines, impairments, but maybe to just put this a little more simply, it sounds like subjective cognitive decline is I feel slower, but testing is normal. In mild cognitive impairment, it’s a case of I am slower, and the tests reflect that, but I’m still functioning independently. And then with major neurocognitive disorder dementia, I am slower, but also I can’t manage my life without help.

Dr. Indu Partha: That’s exactly it.

Dr. Nick Villano: Okay, that makes more sense. But I guess the question I have is, are people progressing through these stages in a really reliable way? If someone has mild dementia, can we expect in three or six months or whatever it might be that it’s going to be moderate?

Dr. Indu Partha: This is really the hard part. When counseling patients, I wish there was some kind of standard example or template that we could provide to our patients to let them know how their dementia trajectory is going to play out. But there are just so many factors that can influence this, like age, a person’s baseline, cognitive function, nutritional status, exercise, blood pressure, obesity. So while we can tell our patients that, “Yes, unfortunately, your cognition is going to decline over time, we just unfortunately cannot really predict how fast this is going to happen or which domains of the brain function are going to be impacted first.”

Dr. Nick Villano: Man, that’s unfortunate, but it does make some sense. So I guess now we should really get into some tests to figure out where on that spectrum our patient is, right? I mean, I think this is going to be really useful, but I’m also a little bit worried. I know that there’s approximately like, 300, give or take, tools for testing cognitive impairment, and that kind of frightens me. Where do we go from here, Indu?

Dr. Indu Parth: Yeah, maybe not quite 300 tests, Nick, but there are a lot and a lot of acronyms to learn, and sometimes it just feels like further testing takes so much time, and it’s hard to administer. But honestly, it’s really worth the effort for our patients. This data can be used over time to let us know where our patients were the last visit compared to where they are now. And from a resource standpoint, it might allow them to get approved for workup or medications as well.

Dr. Nick Villano: Okay. Well, it sounds like it’s definitely needed then. So I’ve heard of the MoCA and the Mini-Mental Status Exam. Should we be using those, and how are they even different?

Dr. Indu Partha: Yeah, so both the MoCA and the MMSE can be used to pick up and track cognitive decline, but the MoCA is actually more sensitive to early disease. And there was actually a study in JAMA IM that showed really great sensitivity for the MoCA in picking up MCI, actually 89%. So I think it varies from clinic to clinic. You sort of pick one screening and just stick with it. Our clinics use the MoCA and just follow our patients over time using that same screening.

Dr. Nick Villano: Okay. Wow, I didn’t know that. So it sounds like there’s some maybe just choice based on where you practice, but for a patient like Ms. Wise, where this is the first time that you’re really wondering if they have cognitive decline, that may be a time that a MoCA could be helpful because it’s more sensitive for early or mild cognitive impairment, right?

Dr. Indu Partha: Exactly. And that’s what we chose to do with Ms. Wise. We administered the MoCA. And just to remind you and our listeners, the MoCA score is going to tell you the severity of the cognitive impairment, and the different questions that are asked are going to tell you which and how many of the key domains are affected in your patient.

Dr. Nick Villano: Okay, that’s really good to know. So we’re not just getting a number, we’re sort of getting this vertical slice of our patient’s health. I mean, it really feels like you’re getting sort of a snapshot of a point in time. So naturally, I would think then that we’re not just doing this once. We’re sort of doing this over and over for our patient to sort of see what direction they’re going and how fast they’re going down it. Does that sound right?

Dr. Indu Partha: Yeah. The MoCA and MMSE are great cognitive tests, but there are limitations to both of them. We need to keep in mind that the tests may be biased towards those who are more educated and those who come from a Western cultural background. We have to keep in mind that you can adjust the MoCA score up to a point if they have less than a high school education. And I do want to introduce two other cognitive tests, Nick, the SLUMS test, and the RUDAS test. We’re going to link these in the show notes, but the SLUMS test can be more inclusive of those across different educational backgrounds, and the RUDAS can be more inclusive across different cultural backgrounds.

Dr. Nick Villano: Oh, wow. I never knew we had those options.

Dr. Indu Partha: There are a lot of options, but which test we choose is actually not the only source of bias. It’s also about the context in which the test was administered. We have to think about the patient. Were they wearing their glasses, their hearing aids when they took the test? Were they mildly delirious in the hospital setting versus at their baseline in the office?

Dr. Nick Villano: Yeah, that’s a great point. One of our discussants, Mary Beth, actually talked about a time that a patient scored a 16 out of 30 on the SLUMS test. That’s when they were in the hospital, but then when she redid it in the office, they scored a 28 out of 30.

Dr. Indu Partha: Yeah, that’s a good reminder, Nick, for us to maybe write a qualifier next to a cognitive score. Maybe we’re indicating that this is their score in the hospital, or wearing their hearing aids, or missing their glasses.

Dr. Nick Villano: And even if we choose the right test and we have a qualifier saying exactly how the test was done, the other source of bias to remember is that this test doesn’t tell us exactly what our patients can do. I remember one patient that I cared for whose MoCA score was a bit on the lower side. So when I went in, I was worried about is this person going to be able to take care of themself at home? But I was kind of surprised because the family was just telling me, yeah, they’re living independently, and they’re caring for themselves with some support systems, they’re doing fine. So the chart made it seem like he was doing worse than he really was, and really reminds me that we sometimes miss functional status with this cognitive testing.

Dr. Laura Perry: So the number one thing I want to see on the problem list under the diagnosis of dementia is what is their FAST stage? There are various scales used for the severity of dementia. I’d say the FAST scale is the most commonly used one. Again, because it focuses on function. What can this person still do? And that’s something that I want to update on a pretty regular basis as the person continues to decline.

Dr. Nick Villano: Sorry, what is the FAST scale? I hear FAST, and I’m reaching for the ultrasound.

Dr. Indu Partha: Oh man. Thankfully, no ultrasound needed here, Nick. I would be in huge trouble. So FAST actually stands for Functional Assessment Scale Tool, and there are stages one through seven that basically describe what a patient can do with respect to their activities of daily living. 

Dr. Laura Perry: I tell them think about what a child learns how to do as it’s growing from infant to toddler to child to teenager, to eventually adult, and think about how sophisticated their brain is at each of those times. In a lot of ways in dementia, you lose those cognitive abilities and the functions that come with them in approximately the order that you learned them in reverse over approximately a similar time period.

Dr. Nick Villano: Yeah, capturing all this information for a patient with cognitive issues, it can feel intimidating. But our awesome CORE IM friend and geriatrician, Dr. Brooke Lubinski, had a great recommendation. She recommends including a one-liner in a patient’s chart that tells providers where’s the patient living? What stage of cognitive impairment are they in? and what is their functional status? What can they do?

Dr. Indu Partha: Can I tell you how much I loved this tip? I find it just so useful to develop this sort of functional status one-liner using a current FAST score or even just a description of what our patient is able or unable to do. And some geriatricians I talk to actually say that when dementia gets more advanced, they kind of stop using the MoCA or MMSE and the functional description really becomes the main thing that they’re following. So, for example, Ms. Wise is a 77-year-old woman living alone in a trailer with a MoCA of 24 out of 30 and a fast score of 4, or maybe you say a 77-year-old woman living alone who is independent of her ADLs but needs assistance with medication management, appointment making, and paying bills.

Dr. Nick Villano: This would be so helpful for me when I’m admitting a patient and knowing exactly what has changed from their baseline as a hospitalist. I feel very seen right now, but okay, so if we want to describe exactly what a patient can do, sounds like we can use this FAST tool, or you said we can just sort of describe what ADLs or IADLs they can do. Right. But can you remind me one more time what exactly are ADLs and IADLs?

Dr. Indu Partha: Thanks for asking Nick, because I think it’s really important to remember the difference between ADLs and IADLs. So ADLs are those activities that one needs to take care of themselves, bathing, dressing, eating, toileting, and transferring. And my patient, Ms. Wise, was okay in this regard. IADLs, the Instrumental Activities of Daily Living are the activities that one needs to take care of their life. Managing medications and finances, preparing meals, housekeeping and driving. And this is where Ms. Wise needed help.

Dr. Nick Villano: This is a callback for me to the five Pearls episode in geriatric care. And they talked about how a patient not trimming their toenails can actually be an indication of functional independence. I mean, it sounds arbitrary, but these are things that we need to do to maintain our daily health, and some of these things can really be early signs. So it sounds like speaking practically, I can imagine that asking someone about “can you prepare meals?” can be useful because if they can’t, maybe you look into meal services. But as you collect all this information, are you using it holistically in any other way?

Dr. Indu Partha: I think we need to keep in mind, Nick, that history is really key in our patients with dementia. It’s going to allow us to see what’s happened and what’s changed with our patients since the last time we saw them. Do they need more help now? Are there safety concerns that didn’t exist before? Understanding the changes in ADLs and IADLs is really going to help me know what I need to plan for next.

Dr. Nick Villano: Got it. That’s really helpful. So it sounds like what we’re saying here is that we really have two buckets to think about for these patients. The first bucket is all about tracking someone’s cognitive status using tools like the MoCA or the MMSE over time. And the second bucket are the tools we have to track someone’s functional status, whether that’s something formal like the FAST or even just a direct review and description of their ADLs and IADLs. So the next clinic note, the next discharge summary that you’re writing, try to actually include both of these buckets and describe what you’re actually seeing in the patient from a cognitive and functional standpoint.

Dr. Indu Partha: Perfectly said, Nick. I think one of the things that I really find with taking care of a patient with dementia is that our questions can lead to more questions. We had identified the places where Ms. Wise needed help, but there was just no way for us to make it happen. We couldn’t move in with her to ensure she was taking care of herself. Her friend, who was a caregiver, couldn’t increase her hours, and Ms. Wise didn’t have the money to get more assistance in the home. So we felt really bad calling her daughter just to inform her that something was off with her mom. But we didn’t know what the diagnosis was, and we weren’t really sure how to fix things. And on top of it all, we were concerned about her safety at home.

Dr. Nick Villano: Man, that is a lot to process. It definitely is a series of steps, and I’m glad that you started when you did. It seems like from here, having an actual diagnosis would make things maybe a little bit more clearer. But I’m also wondering how aggressive we need to be in finding the cause of this patient’s cognitive decline. I mean, I feel like a lot of times I’ve seen people just check a thyroid test of vitamin B12 and then just presume it’s Alzheimer’s disease unless there’s something else going on. What are we supposed to do here?

Dr. Indu Partha: I think that question is one that we are all wondering. So let’s go to deep dive three. How do we determine the etiology of cognitive decline?

Deep Dive 3: How do we determine the etiology of cognitive decline?

Dr. Nick Villano: Okay, so we’ve established that we’re worried about this patient and we’re trying to figure out next steps and we’re saying the first step is to try to figure out what is causing the cognitive decline as best as we can. That sounds great, but I just feel like these disease processes are universally challenging to diagnose, let alone treat. I mean, how important is it really important to pinpoint the exact type of neurocognitive disorder that a patient has?

Dr. Indu Partha: What I really picked up on from my conversations with our discussants is that there aren’t an extensive number of diagnostic tests looking at the etiology of dementia. The testing is really targeted towards making a diagnosis that has disease-modifying medications available, like Alzheimer’s disease, and in addition to that, to allow the patient and their loved ones to plan for the future.

Dr. Nick Villano: That makes sense. So the first thing that we already did was identify that something’s going on, sort of get a sense of how bad it is, and what they’re able to do, what their functional status is. But it sounds like, in looking for an etiology, we’re hoping that this can guide treatment and also give us a sense of overall progression and prognosis.

Dr. Indu Partha: Exactly, Nick. I think we really need to keep in mind that the point of doing a workup for a diagnosis is to see if we can intervene with some treatment and have some impact on prognosis. So for instance, if we have a patient who has already been declining for 10 years and has reached a point where they are unfortunately dependent on others for ADLs and IADLs, we probably realize that there’s not going to be any treatment intervention that is approved for this advanced stage of neurocognitive decline. And the prognosis seems pretty clear, we are not going to be able to make them independent. Again. In contrast, though, if a formerly high-functioning individual is noted to be in the early stages of dementia, we may actually be able to intervene with some disease-modifying medication, and we may be able to help this individual better understand the prognosis and the trajectory that they can expect.

Dr. Gad Marshall: So I would say that in terms of prognosis and not just prognosis but what to expect next, the etiology certainly makes a difference. And I think a lot of what we do with patients and families is education and maximizing their quality of life. And so I think that it’s important for that reason. I would say that it’s important for treatment purposes as well, in terms of our medication options.

Dr. Nick Villano: So now that we’ve gone over why we’re doing this testing, let’s go through the actual steps we need to do a full diagnosis. The first step, it sounds like we already did. I mean, we’re ruling out mimics of dementia. We assess for depression. We made sure they weren’t on any medications that can affect cognition. We evaluated their sleep and their hearing. And then of course there’s biochemical testing that I think a lot of us are familiar with, Treponemal testing, vitamin B12, TSH, and of course we can’t forget HIV testing. But then, I mean, once we’ve done this and we’re really just left with the actual dementia diagnoses, I mean, that’s where I feel like I’m often at a loss because I think a lot of them are pathologic diagnoses, but we’re not doing brain biopsies for these patients. So I mean, are we often just looking at their clinical presentation and their pattern of symptoms?

Dr. Indu Partha: I mean, we don’t want to discount utilizing clinical presentations to help us make a diagnosis. I mean, as we all learned, dementia subtypes can present in pretty characteristic ways like Lewy body dementia, for instance. Patients can often have hallucinations or sleep disturbances. And I think most of us are familiar with the signs and symptoms of Parkinsonism with cogwheel rigidity and mass faces. And of course, frontotemporal dementia is often manifesting with behavioral changes such as disinhibition or anhedonia. And with vascular dementia, it may not be so much clinical symptoms, but we usually have a prior medical history of cerebrovascular disease or old imaging that shows prior infarcts.

Dr. Nick Villano: Right. I definitely understand that if you have typical symptoms that you might be thinking of one of these specific dementia subtypes. But what if you don’t have symptoms that are very suggestive of one of these dementia subtypes? I mean, I guess I would be wondering is this Alzheimer’s or is it just one of the other diseases? And it’s just early on because Alzheimer’s doesn’t really have clear pathognomonic findings. Right. Isn’t that just sort of like a diagnosis of exclusion?

Dr. Indu Partha: Yeah, I mean I think in the past, definitely Nick, if our patient didn’t kind of fit into one of these other categories, we just kind of dump them into an Alzheimer’s bucket. But now we actually can do some specific testing for Alzheimer’s disease, and to kind of get us PCP started, Dr. Marshall recommends an MRI as the first-line study. And if that’s not an option for our patient, then a head CT would be a second choice.

Dr. Nick Villano: Oh really? What would an MRI show you?

Dr. Indu Partha: So stay with me here with MRIs. In Lewy body dementia, you’re going to typically see some atrophy, but with hippocampal sparing and with frontotemporal dementia, as the name would suggest, you see atrophy in the frontal and temporal lobes. Whereas vascular dementia, like we mentioned, may show some prior ischemic infarcts. And in the past if we didn’t see those findings, we just basically said Alzheimer’s disease. But now we know that specific findings like medial temporal lobe and hippocampal atrophy can be pretty suggestive of Alzheimer’s disease. And while they’re not definitive findings, if we’re already considering Alzheimer’s disease as a diagnosis for our patient, these findings on MRI can definitely help strengthen our confidence in making this diagnosis.

Dr. Nick Villano: Got it. That’s really helpful. I didn’t know that. But if I do know anything about imaging, it’s that if there’s a new way to use a test, it means a very specific protocol that we’re going to have to order to make it happen. Right? There must be some kind of fancy new name for these MRIs.

Dr. Indu Partha: Honestly, Nick, I think this is probably a good time to pick up your phone and call radiology and then save that exam on your quick orders because I can’t lie, I can’t tell a T1 from a flare.

Dr. Nick Villano: Yeah, same flare just still makes me think of off space. But it sounds like, I mean, how practical is getting this test? I mean a specialized MRI protocol, is that pretty expensive?

Dr. Indu Partha: Believe it or not, it’s actually got good Medicare coverage for routine use in the workup of dementia. I mean, obviously, you’re going to need to clearly document the clinical symptoms that prompted you to start this workup.

Dr. Nick Villano: Got it. Okay. So MRIs can diagnose different forms of dementia. And in Alzheimer’s disease, we’re not just looking for lack of other findings, we’re actually looking for typical findings of hippocampal and medial temporal lobe atrophy. And that can increase our concern for Alzheimer’s disease. But you said that it wasn’t a hundred percent diagnostic. I mean, what other testing could we do, and in what patients are we doing further testing to confirm that diagnosis?

Dr. Indu Partha: It’s actually quite an exciting time now, Nick. It’s pretty amazing that there are now new tests that can help us make the diagnosis of Alzheimer’s disease. I mean, these are things like PET scanning that are going to show decreased activity in those areas that we spoke about before, the hippocampus and the medial temporal lobe. We might see amyloid on amyloid PET imaging, which as we all learned, is pretty classic of Alzheimer’s disease pathology. And you can also get CSF findings like high tau levels, and even newer plasma biomarkers can help make the diagnosis.

Dr. Nick Villano: That’s really interesting, but also seems like a lot to put someone through, especially someone who’s dealing with cognitive impairment, PET scans, lumbar punctures. Is that why we’re not doing this more often?

Dr. Indu Partha: Yes. I think this testing is going to be reserved for patients who have an unclear diagnosis. Perhaps their MRI and their clinical symptoms are equivocal, and we’re not really sure if we can rule out other types of dementia or if we have a patient who has confirmed Alzheimer’s disease, testing for amyloid on an amyloid PET scan can help qualify them for specific treatments. Or perhaps they’re early in their course of cognitive decline, and we don’t know what their trajectory is going to look like. But I have to say, Nick, this sometimes feels a little bit aspirational for me. It’s just hard for me to see a lot of the patients that we see in our clinics being able to show up for all of this testing, either due to finances, insurance concerns, or just lack of family and caregiver support.

Dr. Nick Villano: Yeah, that makes a lot of sense. I mean, it sounds like we have to basically be selective about who we’re doing testing for and have a good reason to do it. And I mean, really what it sounds like is that these patients where we’re unsure thinking about other testing, these are the patients. We’re also referring to neurology to get more input there. But it sounds like MRIs are a good starting place. Is that something that you can order as a PCP?

Dr. Indu Partha: Yeah, I love the fact that we can get a lot done for our patients with dementia. So primary care folks, remember we can handle a lot. Before we refer to a specialist, we need to make sure there aren’t any metabolic factors at play. Look over our patient’s medications and screen for depression. We can obtain the lab work such as the TSH, the vitamin B12 Treponemal testing and HIV, and then order first-line imaging and MRI or a CT scan if that’s not available.

Dr. Nick Villano: That’s a great summary. And of course, I want to also include to keep an eye out during your workup for any typical presentation of symptoms that could suggest a specific type of dementia. And if you can do all that yourself, I’m sure your patients would be excited about avoiding a six-month wait for a specialty clinic. But as we said, some patients do need to see neurology. We said specifically those with an unclear or atypical presentation or those where we have a diagnosis, we’re just considering advanced therapies. What does that process look like?

Dr. Gad Marshall: And if there’s an atypical presentation, I think you can have somebody who has more of a language predominant presentation or visual perception presentation or executive dysfunction, and you’re not sure what you’re dealing with referred to a specialist. Maybe they need neuropsychological testing to really break down what’s going on.

Dr. Nick Villano: Okay, so break this down for me. We kind of talked about typical presentations, but what could an atypical presentation look like exactly?

Dr. Indu Partha: So patients can present with a significant deficit in an area like language or visual perception or maybe executive functioning. And sure, we could blame any and all of these on changes seen in dementia, but there are going to be other illnesses that we need to ensure we are not missing that can cause the same symptoms. I mean things like brain tumors or seizures, encephalitis, stroke, or even pseudodementia caused by major depressive disorder.

Dr. Nick Villano: Got it. So it sounds like we said that we’re empowered to start the workup, but if anything atypical shows up, a specialist can help us work through that differential, and that we should probably have a low threshold to reach out if we’re worried anything else might be going on.

Dr. Indu Partha: And the subspecialists will often do more testing to confirm diagnosis using newer biomarkers to help track disease or help patients qualify for specific treatments. Dr. Marshall, for instance, orders the amyloid PET to confirm an Alzheimer’s diagnosis if he’s considering treatment with the new monoclonal antibodies in town, Lecanemab or Donanemab. He also uses the amyloid PET for atypical presentations or to help with prognostication.

Dr. Nick Villano: Got it. So to summarize, we said as a PCP or general medicine doctor, we’re really focusing on ruling out non dementia diagnoses, doing the blood workup, doing imaging, but for anything atypical, we’re really relying on our subspecialists to try and make sure we’re not missing something here, and also make sure that they’re using these newer biomarkers to track disease or newer imaging to see if people qualify for specific treatments that we’re going to talk about in the next episode.

Dr. Indu Partha: Exactly. So, bringing back our case with Ms. Wise, we did her lab testing, and her B12 and TSH were normal as we expected. She unfortunately had a lot of issues with scheduling and transportation, but finally got the MRI done, and it was suggestive of Alzheimer’s disease. She really didn’t have any other atypical findings in her history or exam that suggested other forms of dementia. So we felt pretty confident in giving her a diagnosis of Alzheimer’s.

Dr. Nick Villano: Got it. Wow. Okay, so we have a diagnosis. What did you do with that? I mean, how did you break the news of this diagnosis to Ms. Wise and her daughter, and did you end up starting on one of those fancy new mAbs?

Dr. Indu Partha: Well, Nick, we have covered a ton today, and I’m sorry to say you’re just going to have to wait. You and the rest of our listeners are going to get the rest of the story in episode 2, so make sure to tune in next time.

Dr. Nick Villano: Indu leaving me hanging. Alright, I will be back for part two and I hope all of you will be too. Let’s find out what happened with Ms. Wise and talk about next steps in her care.