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Anti-amyloid therapies provide the first FDA-approved option to alter AD pathology, but an understanding of overall utility and value to patients remains in its infancy. In this episode, Teshamae Monteith, MD, FAAN, speaks with David S. Geldmacher, MD, FACP, FANA, author of the article “Treatment of Alzheimer Disease” in the Continuum® December 2024 Dementia issue. Dr. Monteith is the associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida. Dr. Geldmacher is a professor and Warren Family Endowed Chair in Neurology and the director of the Division of Cognitive and Behavioral Neurology, Department of Neurology, Marnix E. Heersink School of Medicine at the University of Alabama at Birmingham in Birmingham, Alabama. Additional Resources Read the article: Treatment of Alzheimer Disease Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @headacheMD Transcript Full interview transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Monteith: This is Dr Teshamae Monteith. Today, I'm interviewing Dr David Geldmacher about his article on treatment of Alzheimer's disease, which appears in the December 2024 Continuum issue on dementia. Welcome to our podcast, Dr Geldmacher. How are you?  Dr Geldmacher: I'm very well, thank you. It's a pleasure to be here.  Dr Monteith: Yeah. So, why don't you introduce yourself to our audience? Dr Geldmacher: Sure. I'm David Geldmacher. I'm a professor of neurology at the University of Alabama in Birmingham and I lead the division of Cognitive and Behavioral Neurology.  Dr Monteith: So, I'm really excited about this, to personally learn, and I know that or neurology community is also really excited about this interview. So, why don't we start off with your main objective.  Dr Geldmacher: So, my main goal in the article was to review the FDA-approved pharmacologic treatments for dementia. There's lots of ways of thinking about treatment of dementia; psychosocial, caregiver support, and so forth. But I really wanted to focus on the issues of drug treatment because that's what has been our backbone for a long time and now has recently expanded.  Dr Monteith: Why don't we talk a little bit about, first of all, the boom in the field? What's that been like?  Dr Geldmacher: So, the big change in the field is over the last several years, we've had treatments become available that actually attack the underlying Alzheimer pathology, and that's new and different. For decades, we've been able to treat the symptoms of the disease, but this is the first time we've really been able to get to the root of the pathology and look toward removing amyloid plaques from the brain.  Dr Monteith: Let's step back a little bit and talk about the framework of diagnosis and how that leads into the therapeutic potential. I know you're going to dive into some of the biologics, but we should probably talk about the kind of holistic approach to considering the diagnosis. Dr Geldmacher: Sure. So, you know, when someone comes to the clinic with memory complaints, our question we have to ask is, is this neurologic origin, a structural origin like Alzheimer's disease or vascular dementia? Are there complicating factors, the software issues of mood disorders and sleep disorders and pain that can all magnify those symptoms? The clinical reasoning is a critical part of that, but in Alzheimer's disease, typically the problems revolve around difficulty forming new memories of events and activities, the episodic memory. And then it's often accompanied by changes in word finding and semantic knowledge. And those are the things that we look for in the clinic to really point toward an AD diagnosis. And then we support it with exclusion of other causes through blood work and identification of patterns of brain atrophy on MRI. And then most recently in the last couple of years, we've been able to add to that molecular imaging for amyloid with PET scans as well as, most recently, blood-based biomarkers for Alzheimer's pathology. So, it's really been a revolution in the diagnosis over these last several years.  Dr Monteith: And when approaching patients or populations of individuals, there seems to be a real full spectrum with looking at the societal burden, the biological impact, of course, risk factors of primary prevention, and now this whole area of brain health and secondary prevention. How do you kind of tie all of this together when talking to patients and family members?  Dr Geldmacher: Sure. So, the approaches for brain health apply to everyone. In basically every clinic visited, our brain aging and memory clinic, we reviewed lifestyle approaches to brain health like regular physical exercise, healthy diet, cognitive and social stimulation. And those are fundamental to the approach to everyone, whether they have cognitive impairments that are measurable or not. These are all things that are good for our brain health. And then, you know, focusing on the vascular risk factors in particular and working with the patient and their primary care team to ensure that lipids and blood sugar and blood pressure are all in good healthy ranges and being appropriately treated.  Dr Monteith: You know, there's this kind of whole considerations of clinically meaningful endpoints and clinical trials, and even when we're talking to our patients. What would you say the field has kind of identified has the best endpoints in helping patients? Would you call it impaired daily function? Is that like the best hard endpoint? Obviously, there are other things such as caregiver burden, but you know, how do you approach assessing patients? Dr Geldmacher: Defining the endpoints is very difficult. Typically, if we talk to patients and their families, they would like to have better memory or improve memory. How that applies in everyday life actually is daily function. And so, we focus very much on daily function. And when I talk about our therapies, whether they're symptomatic therapies or the new disease-modifying therapies, I really talk about maintenance of function and delays and decline or slowing of decline, helping to foster the person's independence in the activities that they have and be able to sustain that over the longer term.  Dr Monteith: And when thinking about diagnosis- and we're going to get into treatments, but when thinking about the diagnosis, and of course, it's full-spectrum from mild cognitive impairment to moderate and severe forms of dementia, but who should have CSF testing and PET imaging? Obviously, these are invasive, somewhat invasive and expensive tests. Should all people that walk in the door that have memory complaints? How do you stratify who should have tests? Dr Geldmacher: I think about this in a big funnel, basically, and the starting point of the funnel, of course, is the person with memory complaints. Then there's that neurologic reasoning. Are these memory complaints consistent with what we expect from the anatomy of Alzheimer's disease, with atrophy in in the hippocampus and temporal lobe? Do they have episodic memory loss or not? That first step is really trying to characterize, do the clinical patterns act like those of Alzheimer's disease or not? And then we follow the Academy of Neurology guidelines, looking for reversible sources of cognitive decline, things like B12 deficiency and depression, sleep disorders and the like, and try to exclude those. We start with structural imaging with everyone, and MRI, typically, that will help us understand vascular burden and patterns of atrophy, looking for things like mesial temporal atrophy or precuneus atrophy that are characteristic of Alzheimer's disease. If those things are all pointing in the direction of AD as opposed to something else, then typically before moving on to CSF or PET scan, we will use blood-based biomarkers, which are one of the big changes in the field in the last year or so, and there are now multiple panels of these available. The downside is they are typically not covered by insurance. On the other hand, they can really help us identify who is likely to have a positive PET scan or positive findings on CSF. We start to provide that counseling and information to the patient before they get to those more definitive tests. We can push people in the other direction. We can say, your blood-based biomarkers are negative or do not indicate AD as the most likely source of your condition now, so let's treat other things. Let's see what else we can focus on. The blood-based biomarkers are now, in our clinic at least, the critical choke point between the routine workout that we've always done on everyone and then the more advanced workup of proving amyloid pathology with CSF or a PET scan. Dr Monteith: How sensitive are those blood biomarkers and how early are they positive?  Dr Geldmacher: The sensitivity is generally pretty good, in the ninety plus percent range on average and it depends on which panel. And as you point out, when in the course of symptoms that they're done, we know that they become positive and presymptomatic or asymptomatic people. We're using these kinds of markers to screen people for prevention trials. So, I think when someone is symptomatic, they're a good indicator of the presence or absence of AD pathology. Now that doesn't mean the AD pathology is the sole cause of their symptoms. And so, we still need to think about those other things like sleep and mood and so forth. But they do point us in the in the direction of Alzheimer's change.  Dr Monteith: So why don't we talk about some of the more standard older treatments, and it's also important to leave with kind of some rational approach to when we start and what should we be counseling our patients on. So why don't we start with the older, you know, choline esterase inhibitors and then some of the MDA- I guess there's only one modulator, SEPTA modulator. Dr Geldmacher: So, I've been really fortunate in my career span, the time from the first of those symptomatic agents reaching the market in 1993 to seeing the disease modifying drugs enter the market now. I think most neurologists actually have entered practice after those clinical trials of the colon esterase inhibitors were published. So, one of my goals in this article was to review that primary data and what can we expect from those symptomatic drugs. We know that they are inconsistently effective in mild cognitive impairment, and the Academy of Neurology guidelines says there is not strong evidence to use them in mild cognitive impairment. But in mild AD and beyond, the cholinesterase inhibitors provide meaningful benefits. They delay decline, they can delay nursing home placement. They reduce overall costs of care. So, I think they provide real value. So, in the article I have reviewed what the data looked like on those. My approach is to start with oral Donepezil at five milligrams and increase it to ten in everyone who tolerates the five. If for whatever reason the oral Donepezil is not well tolerated, I'll switch to transdermal rivastigmine to help improve tolerability. There are very few head to head comparisons, but nothing suggests that one of the cholinesterase inhibitors is superior to the other for clinical outcomes, and there's no evidence to support conjoint use of more than one at a time. Should someone be showing decline then on typical cholinesterase inhibitor therapy - and people will, it's often delayed, but the decline will reemerge - then I will add the NMDA receptor, a modulator memantine and titrate that up to full dosing, either 10 mg twice a day for the conventional release or 22 mg extended release. And at that point we're sort of on maximal pharmacologic therapy for Alzheimer's disease. These agents can provide some benefit in other conditions, they're off-label except for Lewy body disease where rivastigmine is labeled. But they can provide benefit across different conditions. And there's some preliminary data, for instance, of acetylcholinesterase inhibitors being helpful in vascular cognitive impairment. So, I will use them, but I expect the greatest response when someone really does follow the patterns of Alzheimer's disease.  Dr Monteith: And you have a great chart, by the way, and nice figures looking at some of the meta-analyses on cognitive outcomes as well as functional outcomes. So, thank you for that.  Dr Geldmacher: In general, all of those tables favor treatment over placebo in the domains of cognition, daily function, neuropsychiatric symptoms. And it's that consistency of result that lets me know that we really are seeing a drug effect, that it's not a class effect with those, that we really are helping our patients. It's not like some studies are positive and some are negative. They are very consistently positive. Small magnitude, but consistently positive.  Dr Monteith: And I know we have a lot of patients coming in where, at least, their caregivers are complaining about agitation, and sleep is also a problem for others. And so how do you help that patient? I know you have a good algorithm that also you included in your article, but why don't you summarize how we should approach these symptoms? Dr Geldmacher: Sure. So, for nonpsychotic agitation, you know, just restlessness, wandering, pacing and so forth, my first choice is an off-label use of citalopram. And there is good clinical trials evidence to support that. if someone has psychotic agitation that is with delusions or hallucinations and so forth, I think we do need to move to the antipsychotic drugs. And the one drug that is now approved for treatment of agitation and Alzheimer's disease does fall into that antipsychotic category, along with its various black box warnings - and that's brexpiprazole. For many of our patients, getting coverage for that agent is difficult. It's not on many formularies. So, it is something I progress toward rather than start with. Similarly, for sleep, there is one approved agent for sleep, that's a dual orexin agonist. And it shows effectiveness, but can have some negative cognitive effects, and so I tend not to start with that either. My first choice when sleep is the primary issue for our patients with dementia is trazodone, and there are some small, limited studies for it's off-label used to enhance sleep. It's safe, inexpensive, often effective, and therefore it's my first choice. Dr Monteith: So, now let's get into the big conversations that everyone is having. Let's talk about the newer disease modifying anti amyloid therapies. Give us a summary dating back 2021 probably, although we can hold the preclinical work, but let's talk about what is available to our patients. Dr Geldmacher: Sure. And the development of anti-amyloid therapies goes all the way back to 1999. So, it's a pretty long course to get us to where we are today.  Dr Monteith: Yeah, that's why we limited that.  Dr Geldmacher: With that first approved agent with aducanumab in 2021, it received a limited or accelerated approval in FDA parlance. These agents, the aducanumab, lecanemab and donanemab, all approved, are known to remove amyloid pathology from the brain as measured by CSF and/or BIPET. They are amyloid lowering therapies, often called disease-modifying therapies. And across the agents there's some variable results. But if we look at the two with full approval, lecanemab and donanemab, they slow clinical progression by 25% to 35% on average. And that's measured by either cognitive measures or global measures or composite measures, but it's pretty consistent in that range of about one-third slowing. That makes it really difficult to discern in an individual patient, though, because there's so much variability in the progression of the disease already that it can be difficult to tell in one person that these drugs are working. They're also complex to use, so there's a qualification process that involves MRI to exclude things like a high tendency toward hemorrhage. It includes genetic testing for papal E4 status to help us understand the risk for complication, and then once-monthly or twice-monthly infusions with standardized schedule for MRI scanning. So, there's a lot that goes into managing these agents. And they are expensive, and we don't yet know their cost effectiveness. The cost effectiveness of the cholinesterase inhibitors was questioned when they first came out back in the 1990s, and it took five or ten years to really understand that they provided benefit to society and to individuals in those domains of quality of life and return on investment. And we're still learning about that with the disease modifying therapies.  Dr Monteith: So, two questions. One, the case that you presented was an individual having symptoms and kind of voiced their desire to be on these therapies. So, people are going to be asking, coming to clinic asking and then of course, they're going to be people that you select out. So, how do you make that decision to recommend this treatment for patients given the potential risk? Dr Geldmacher: We've got some really good guidance from appropriate use recommendation papers for aducanumab and lecanemab, and I'm expecting one from donanemab fairly soon. But the key is to identify individualized risks, and that involves knowing their APOE4 status, knowing their- whether they've had microhemorrhages in the brain previously, and then documenting that they really do have amyloid pathology with something like PET scan to establish those baselines. I talk to people about the burden of twice-monthly infusions or, now with donanemab, once-monthly infusions. And for instance, for someone who's got a working caregiver, getting to an infusion center twice a month can be a significant burden. And then if there are complications, frequent MRI scans and so forth. So, we talk about the burden of entering into this therapeutic pathway. The reality is that people who are qualified generally want it. I have relatively few folks who have said, no, these risks are more than I'm willing to accept. For decades my patients have said, anything you can do to slow this down, I'm willing to try. And now we're seeing that translated to reality with people willing to accept high-risk, high-cost treatments with the chance of slowing their individual progression.  Dr Monteith: And how do you select between the two treatments? Dr Geldmacher: So far that's been easy because donanemab's not readily available.  Dr Monteith: Outside of clinical trials, right?  Dr Geldmacher: Exactly. For prescription use, it's coming in - the first cases have now been infused - but it's not generally available. Nonetheless, what I will do for patients in this is look at the risk tables. So donanemab appears to have in general some higher rates of the Aria complications, amyloid-related imaging anomalies, and some people are going to be more risk tolerant of that for the payoff of potentially faster response. The donanemab trials restructured that. They did their first assessment of effectiveness. I had amyloid removal at six months and a significant proportion of people were eligible to discontinue treatment at six months because their amyloid was below treatable thresholds. So higher risk, perhaps faster action and fewer infusions for donanemab. Lecanemab we have more direct experience with, and between the two of them, the eighteen month outcomes are pretty much the same and indistinguishable. So are we in it for a quick hit, or are we in it for the long race? And different patients and different families will have differing opinions on where they want to accept that risk and burden and so forth. But so far, the data don't indicate a lot of difference in their longer-term outcomes. We still have plenty to learn.  Dr Monteith: And so, it sounds like, as you mentioned, we're looking at eighteen months out for kind of a hard outcome, and that there is a lot of variability in response rate. How are you tracking patients- you know about the imaging, so just in terms of clinical outcomes and efficacy?  Dr Geldmacher: Sure. So, for Medicare to reimburse on these treatments, people need to be enrolled in a registry program - and there are several of these, CMS runs one of their own. But the requirement for that is, every six months, to do cognitive and functional outcomes through the first two years. Cognitive outcomes are up to the clinician, but things like the mini mental state exam, the MoCA, are appropriate. In our own program, we use something we developed locally called the Alabama Brief Cognitive Screener. As for the cognitive outcomes and then for functional, we use an instrument called the General Activities of Daily Living Scale, but there are many other ADL scales that could be used as well. CMS does not mandate specific tests. Since the progression of the disease is variable to begin with, we don't really know how to interpret these results in reference to whether the drug is working, but I can tell a patient or a family member, your scores are stable, or, you have a decline of three points in this test. That's typical for this duration of illness. But there isn't a good way to know whether the drug is working in this person at this time, at least with our current levels of data.  Dr Monteith: So, I think we have to talk about health equity, and it sounds like Medicare is reimbursing for some of us. We look at different socioeconomic backgrounds, educational backgrounds, race, ethnicity. Not everyone is aware of these treatments. So, how do we get more patients to become aware of these treatments? And how do we get them to more people to help people? Dr Geldmacher: Yeah, I mean, that's- it's a major, major issue of inequity in our population. We've done some work at UAB looking at the flow of members of minority communities into memory clinics. So, we know that the overall population of, and I'll choose, for an example, blacks and African Americans, that they are represented a much higher rate in our overall UAB treatment population than they are in our memory clinic population. So, they're not even getting to us in the specialty clinic at the same rates as other segments of our population. We also know that blacks and African Americans in our population are not receiving PET scans as often as the overall treatment population. So yes, there are real, real problems with access. There are cultural issues behind this as well. And in many communities, a change in cognition, a loss of memory is an expected part of the aging process rather than recognized as a disease. So, people who come to us from minority communities are often further along in the course of cognitive and functional decline and beyond the point where they might qualify for the disease-modifying therapies, where early AD is the sort of defining boundary. So, I think more awareness and more screening in primary care settings, perhaps more community outreach to let people know that changes in memory that affect daily function are not normal as part of the aging process and should be evaluated for intervention. So, there's lots of places in our healthcare community where we could foster better outreach, better knowledge to get more folks access to the medicines. And this is before we even get to cost. Dr Monteith: Yeah, yeah. And obviously, there's some stigma as well.  Dr Geldmacher: That's right.  Dr Monteith: Really recognizing what the issues are and diving and asking those questions and funding research that asks those questions, as you mentioned, is really important. And then you have also a nice area where, you know, looking on the impact of treatments on caregiver-related outcomes, and of course ultimately want to keep patients out of nursing homes and prevent death. And so, can you talk a little bit about that? And, you know, mainly the caregiver burden.  Dr Geldmacher: So, my research in that area goes back a long way now. But I learned early in the course of therapy that many times the outcome that the family is noticing for symptomatic therapies is not a change in the patient's memory per se, but that there is less work involved in the caregiving. Less time is spent in direct caregiving roles. The patient may shadow less and because they have better independent cognition. I remember one family member once told me, the medicine you started is a godsend because now I can go to the bathroom by myself and he's not pounding on the door saying where are you, where are you. He's able to recall long enough that I'm in the bathroom that I have that moment of privacy. That was very meaningful to me to hear that. So. Dr Monteith: Cool. So why don't you just help us wrap this up and just give us, like, three main takeaway points that we should be getting out of your article? Dr Geldmacher: The three points that I would emphasize from my article is that the symptomatic therapies provide meaningful benefits and measurable, consistent, meaningful benefits. The second is that those benefits extend beyond things like cognitive test scores and into things like caregiver well-being and maintenance of independence in the home environment. And the third is that the disease-modifying therapies are an exciting opportunity to modify the pathology, but we still are learning about their cost effectiveness and their long-term benefit both to individuals and to society. But the only way we're going to learn that is by using them. And that was the experience that we gained from the symptomatic therapies that took use in the community for years before we really began to understand their true value. Dr Monteith: Thank you. That was excellent. And I put you on the spot, too.  Dr Geldmacher: No problem.  Dr Monteith: Again, today I've been interviewing Dr David Geldmacher, whose article on treatment of Alzheimer's disease appears in the most recent issue of Continuum on Dementia. Be sure to check out Continuum audio episodes from this and other issues. And thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at contentpub.com/AudioCME. Thank you for listening to Continuum Audio.

A pragmatic and organized approach is needed to recognize patients with symptomatic Alzheimer Disease in clinical practice, stage the level of impairment, confirm the clinical diagnosis, and apply this information to advance therapeutic decision making. In this episode, Aaron Berkowitz, MD, PhD, FAAN, speaks with Gregory S. Day, MD, MSc, MSCI, FAAN, author of the article “Diagnosing Alzheimer Disease,” in the Continuum December 2024 Dementia issue. Dr. Berkowitz is a Continuum® Audio interviewer associate chief medical information officer at the Cleveland Clinic in Cleveland, Ohio. Dr. Day is an associate professor in the Department of Neurology at Mayo Clinic Florida in Jacksonville, Florida. Additional Resources Read the article: Diagnosing Alzheimer Disease Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @AaronLBerkowitz Guest: @GDay_Neuro Full episode transcript available here Dr Jones: This is Doctor Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Berkowitz: This is Dr Aaron Berkowitz, and today I have the pleasure of interviewing Dr Gregory Day about his article on Alzheimer disease, which appears in the December 2024 Continuum issue on dementia. Welcome to the podcast, Dr Day. Would you mind introducing yourself to our audience?  Dr Day: Thanks very much, Aaron. I'm Gregg Day. I'm a behavioral neurologist at Mayo Clinic in Jacksonville, Florida, which means that my primary clinical focus is in the assessment of patients presenting typically with memory concerns and dementia in particular. Dr Berkowitz: Fantastic. Well, as we were talking about before the interview, I've heard your voice many times over the Neurology podcast and Continuum podcast. I've always learned a lot from you in this rapidly changing field over the past couple of years, and very excited to have the opportunity to talk to you today and pick your brain a little bit on this very common issue of evaluating patients presenting with memory loss who may have concerns that they have dementia and specifically Alzheimer disease. So, in your article, you provide a comprehensive and practical approach to a patient presenting for evaluation for possible dementia and the question of whether they have Alzheimer disease. The article is really packed with clinical pearls, practical advice. I encourage all of our listeners to read it. In our interview today, I'd like to talk through a theoretical clinical encounter and evaluation so that I and our listeners can learn from your approach to a patient like this. Let's say we have a theoretical patient in their seventies who comes in for evaluation of memory loss and they and/or their family are concerned that this could be Alzheimer disease. How do you approach the history in a patient like that? Dr Day: It's a great way to approach this problem. And if you're reading the article, know that I wrote it really with this question in mind. What would I be doing, what do we typically do, when we're seeing patients coming with new complaints that concern the patient and typically also concern those that know the best? So be that a family member, close friend, adult child. And in your scenario here, this seventy year old individual, we're going to use all the information that we have on hand. First off, really key, if we can, we want to start that visit with someone else in the room. I often say when talking to individuals who come alone that there's a little bit of irony in somebody coming to a memory assessment alone to tell me all the things they forgot. Some patients get the joke, others not so much, but bringing someone with them really enhances the quality of the interview. Very important for us to get reliable information and a collateral source is going to provide that in most scenarios. The other thing that I'm going to start with, I'm going to make sure that I have appropriate time to address this question. We've all had that experience. We're wrapping up a clinical interview, maybe one that's already ran a little bit late and there's that one more thing that's mentioned on the way out the door: I'm really concerned about my memory or I'm concerned about mom 's memory. That's not the opportunity to begin a memory assessment. That's the opportunity to schedule a dedicated visit. So, assuming that we've got someone else in the room with us, we've got our patient of interest, I'm going to approach the history really at the beginning. Seems like an easy thing to say, but so often patients in the room and their caregivers, they've been waiting for this appointment for weeks or months. They want to get it out all out on the table. They're worried we're going to rush them through and not take time to piece it together. And so, they're going to tell you what's going on right now. But the secret to a memory assessment, and particularly getting and arriving at an accurate diagnosis that reflects on and thinks about cause of memory problems, is actually knowing how symptoms began. And so, the usual opening statement for me is going to be: Tell me why you're here, and tell me about the first time or the first symptoms that indicated there was an ongoing problem. And so, going back to the beginning can be very helpful. This article is focused on Alzheimer disease and our clinical approach to the diagnosis of Alzheimer disease. And so, what I'm going to expect in a patient who has a typical presentation of Alzheimer disease is that there may be some disagreement between the patient and the spouse or other partners sitting in the room with me about when symptoms began. If you've got two partners sitting in the room, maybe an adult child and a spouse, there may be disagreement between them. What that tells me is at the onset, those first symptoms, they're hard to pin down. Symptoms typically emerge gradually in patients with symptomatic Alzheimer disease. They may be missed early on, or attributed or contributed to other things going on in the patient's time of life, phase of life. It's okay to let them sort of duke it out a little bit to determine, but really what I'm figuring out here is, are we talking about something that's happened across weeks, months or more likely years? And then I'm going to want to listen to, how did symptoms evolve? What's been the change over time? With Alzheimer disease and most neurodegenerative diseases, we expect gradual onset and gradual progression, things becoming more apparent. And at some point, everyone in the room is going to agree that, well, as of this state, there clearly was a problem. And then we can get into talking about specific symptoms and really begin to pick that apart the way that we traditionally do in any standard neurological assessment. Dr Berkowitz: Fantastic. And so, what are some of the things you're listening for in that history that would clue you in to thinking this patient may indeed be someone who could have Alzheimer's disease and going to require a workup for that diagnosis? Dr Day: It's pretty common when I have new trainees that come to clinic, they just head into the exam room and they sort of try to approach it the way that we would any patient in the emergency department or any other clinical scenario. The challenge with that is that, you know, we're taught to let the patient speak and we're going to let the patient speak - open-ended questions are great - but there's only so many questions you need to sort out if someone has a memory problem. And memory is really only one part, one component, of a thorough cognitive evaluation. And so, I'm going to help by asking specific questions about memory. I'm going to make sure that there is memory challenges there. And whenever possible, I'm going to solicit some examples to back that up, add credibility and sort of structure to the deficits. I'm also going to choose examples that help me to understand how does this concern, or this complaint, how does that actually affect the patient in their day-to-day life? Is it simply something that they're aware of but yet hasn't manifested in a way that their partner knows about? Is it to a level where their partner's actually had to take over their responsibility? It's causing some difficulties, disability even, associated with that. That's going to be important for me as I try to understand that. So, I'll ask questions when it comes to memory, not just, you know, do you forget things, but do you manage your own medications? You remember to take those in the morning? Do you need reminders from your partner? What about appointments; health appointments, social appointments? Are you managing that on your own? Sometimes we need a little bit of imagination here. Partnerships, and particularly those who have been together for a long time, it's natural that different people are going to assume different responsibilities. And so, might have to say, Imagine that you went away for the weekend. Would you worry about your partner remembering to take their medications over that time frame? That can help to really solidify how much of an impact are these challenges having on a day-to-day basis. I may ask questions about events, something that they maybe did a couple of weeks ago. Is the patient likely to remember that event? Are they going to forget details? Maybe the most important of all, with each of these, when there's a yes or an affirmation of a problem, we want to be clear that this represents a change from before. We all have forgetfulness. Happens on a day-to-day basis, and we all pay attention to different details, but what we're concerned about and typically the reasons patients want to come and see us as neurologists is because they've noticed a change. And so, I'm going to focus in on the things that represent a change from before. After I've discussed memory, I think it's really important to talk about the other domains. So, how is judgment affected? Decision-making?  In a practical way, we often see that borne out in financial management, paying the bills. Not just paying them on time and consistently, but making wise choices when it comes to decisions that need to be made. You're out at a restaurant. Can you pay the bill? Can you calculate a tip? Can you do that as quickly and as efficiently as before? Are we starting to see a breakdown in decision-making abilities there? We can sometimes lump in changes in behavior along with judgment as well. The patient that you know, maybe isn't making wise choices, they've picked up the phone and given their social security number out to someone that was calling, seeming to be well-meaning. Or maybe they've made donations to a few more institutions than they would have otherwise? Again, out of- out of order. Again, something that could be atypical for any individual. Looking for behavioral changes along with that as well. And then I'm going to talk about orientation. What's their ability to recognize days of the week, date of the month? Do they get lost? Is there concerns about wayfinding? Thinking about that, which is really a complex integration of some memory, visuospatial processing, judgment, problem solving, as we look to navigate our complex world and find our way from point A to B. And then I like to know, you know, what are they doing outside of the home? What are they doing in the community? How are they maintaining their engagement? Do they go to the store? Do they drive? An important topic that we may need to think about later on in this patient 's assessment. And inside the home? What responsibilities do they maintain there? Are the changes in decision making, memory problems, are they manifesting in any lost abilities inside the home? Cooking being a potentially high-risk activity, but also using typical appliances and interacting with technology, in a way that we are all increasingly, increasingly doing and increasingly reliant on. And last but not least, you know, maybe the one that everyone wants to think about, well, I can still manage all of my own personal care. Well, good news that many of our patients who have early symptoms can manage their own personal care. Their activities of daily living are not the big problem. But we do want to ask about that specifically. And it's not just about getting in the shower, getting clean, getting out, getting your teeth brushed. Do you need reminders to do that? Do you hop in the shower twice because you forgot that you'd already been in there once during the day? And so, asking some more of those probing questions there can give us a little bit more depth to the interview and really does sort of round out the overall comprehensive history taking in a patient with a memory or cognitive concern. Dr Berkowitz: Fantastic. That was a comprehensive master class on how to both sort of ask the general questions, have you noticed problems in fill in the blank memory, judgment, behavior, orientation, navigation and to sort of drill down on what might be specific examples if they're not offered by the patient or partner to try to say, well, in this domain, tell me how this is going or have you noticed any changes because the everyone's starting from a different level cognitively based on many factors. Right? So, to get a sense of really what the change is in any of these functions and how those have impacted the patient's daily life. So, let's say based on the history, the comprehensive history you've just discussed with us, you do find a number of concerning features in the history that do raise concern for dementia, specifically Alzheimer's disease. How do you approach the examination? We have the MoCA, the mini-mental. We have all of these tools that we use. How do you decide the best way to evaluate based on your history to try to get some objective measure to go along with the more subjective aspects of the history that you've ascertained? Dr Day: And you're honing in on a really good point here, that the history is one part of the interview or the assessment. We really want to build a story and potentially and hopefully a consistent story. If there are memory complaints, cognitive complaints from history, from reliable- that are supported by reliable collateral sources, we're going to expect to see deficits on tests that measure those same things. And so, I think that question about what neuropsychological measures or particular bedside tests can we integrate in our assessment is a good one. But I'll say that it's not the end-all-be-all. And so, if you've got a spouse, someone that lives with an individual for twenty or thirty years, and they're telling you that they notice a change in daily activity and it's impairing their day to day function, or where there's been some change or some concern at work, that's going to worry me more than a low score on a cognitive test with a spouse saying they haven't noticed any day-to-day impact. And so, we're going to take everything sort of in concert and take it all together. And it's part of our job as clinicians to try to process that information. But often we're going to see corroborating history that comes from a bedside test. He named a few that our listeners are probably pretty familiar with. I think they're the most common ones that are used. The Mini-Mental State Exam, been in practice for a long time. All the points add up to thirty and seems to give a pretty good sample of various different cognitive functions. The Montreal Cognitive Assessment, another favorite; a little bit more challenging of a test, I think, if we're if we're looking at how people tend to perform on it. And like the MMSE, points add up to thirty and gives a pretty good sample. There are others that are out there as well, some that are available without copyright and easy for use in clinical practice. The Saint Louis Mental Status Exam comes to mind. All these tests that we're willing to consider kind of share that same attribute. They can be done relatively quickly. They should sample various different aspects of function. There should be some component for language reading, spoken, spoken word, naming items, something that's going to involve some kind of executive function or decision making, problem solving. Usually a memory task where you're going to remember a set of words and be asked to recall that again later. So, learn it, encode it, and recall it later on. And then a few other features, I mean, some of them, these tests, most of these tests use some sort of drawing tasks so that we can see visuospatial perception and orientation questions about date, time, location, sort of the standard format. Any of these tests can be used aptly in your practice. You're going to use the one that you're most comfortable with, that you can administer in a reasonable amount of time and that seems to fit with your patient population. And that's the nuance behind these tests. There are many factors that we have to take into account when we're picking one and when we're interpreting the test results. These tests all generally assume that patients have some level of traditional sociocultural education that is westernized for the most part. And so, not great tests for people that aren't well into integrated into the community, maybe newcomers to the United States, those that have English as a second, third, or fourth language, as many of our patients do. Statements like no ifs, ands, or buts may not be familiar to them and may not be as easy to repeat, recall and remember. And so, we want to weigh these considerations. We may need to make some adjustments to the score, but ideally, we're going to use these tests and they're going to show us what we expect and we're going to try to interpret that together with the history that we've already ascertained. When I obtain that history and I'm thinking about memory loss, I'm going to look at the specific domain scores. And so, if I'm using the mini mental state examination thirty point test, but three questions that relate to relate to recall. Apple, penny, table. And so, depending on how our patients do on that test, they could have an overall pretty good score. Twenty seven. Oh, that looks good. You're in the normal range according to many different status. But if I look at that and there's zero out of three on recall, they could not remember those three items, that may support the emergence of a memory problem. That may corroborate that same thing on the MoCA, which uses five-item recall, and other tests in those same parameters. I mentioned some other caveat cities testing. Are patients who are presenting with prominent language deficits important part of cognition. They can't get the words out. They can't frame their sentences. They may really struggle with these tests because a lot of them do require you to both understand verbal instructions and convey verbal instructions. People with prominent visual problems, either visual problems that come because of their neurodegenerative disease and so part of cognition, visual perceptual problems, or people who simply have low vision. Are there difficulties for that? These tests require many people to read and execute motor commands, to draw things, to follow lines and connect dots, all very difficult in that setting. And so, we have to be cautious about how we're interpreting test results in patients who may have some atypical features or may arrive with sort of preexisting conditions that limit our ability to interpret and apply the test to clinical practice.  Dr Berkowitz: Really fantastic overview of these tests, how to use them, how to interpret them. It's not all about the number. As you said, it depends if all the points are lost in one particular domain, that can be salient and then considering, as you said, the patient 's background, their level of education, where English falls in their first language, second, third or fourth, as you said, and then some of the aspects of the MoCA, right, are not always as culturally sensitive since it's a test designed in a particular context. So, let's say your history and exam are now concerning to you, that the patient does indeed have dementia. Tell us a little bit about the next steps in the laboratory neuroimaging evaluation of such a patient?  Dr Day: I've got a history of memory and thinking problems. I've got some corroborating evidence from bedside cognitive testing, a normal neurological exam. This is where we think about, well, what other tests do we need to send our patients for? Blood testing really can be pretty cursory for most patients with a typical presentation who have typical risk factors, and that can include a thyroid study and vitamin B12. So, measuring those in the blood to make sure that there's no other contributions from potential metabolic factors that can worsen, exacerbate cognitive function. And pretty easy to do for the most part, if patients have other things in their history, maybe they come from a high-risk community, maybe they engage in high risk behaviors, I may think about adding on other tests that associate with cognitive decline. We'll think about the role of syphilis, HIV, other infections. But generally, that's when it's driven by history, not a rule of thumb for me in my typical practice. But beyond the blood tests, neuroimaging, some form of structural brain imaging is important. A CT scan will get you by. So, if you have a patient that can't get in the scanner for one reason or another or won't get in the scanner, or you don't have easy access to an MRI, a CT scan can help us in ruling out the biggest things that we're looking for. That's strokes, hemorrhages, and brain masses. So other things that obviously would take us down a very different path, very different diagnosis and very different treatment approach. An MRI, though, is going to be preferred, not only because it gives us a much higher-resolution view, but also because it helps us to see sort of regional areas of atrophy. It's a sensitive scan to look for small vessel disease, tiny strokes, tiny bleeds, microhemorrhages that again might point towards meteorology for us. Of course, it's better at finding those small masses, whether they be metastasis or primary masses, that could give us something else to consider in our diagnostic evaluation. I get an odd question often from patients, well, can you see Alzheimer's disease on an MRI? And the true answer to that is no, you can't. Can we see the signs of Alzheimer's disease? Sure, in some patients, but really what we see on an MRI is a reflection of neurodegeneration. And so, we see evidence of tissue loss and typically in areas that are most often involved early on in Alzheimer's disease. The hippocampus, the entorhinal areas around the hippocampus, we may see atrophy there. We may see biparietal atrophy, and of course, as the disease progresses, we're going to see atrophy distributed throughout other areas of the brain. But if you're looking for atrophy, you've got to have a pretty good idea what's normal for age and what you expect in that patient population. So, I do encourage clinicians who are assessing patients routinely, look at your own images, look at the images for patients with and without cognitive impairment. So we develop a pretty good sense for what can be normal for age, and of course work with our colleagues in radiology who do this for a living and generally do an excellent job at it as well.  Dr Berkowitz: Perfect. So, you're going to look for the so-called reversible causes of dementia with serum labs, structural imaging to either rule out or evaluate for potential structural causes that are not related to a neurodegenerative condition or patterns of regional atrophy suggestive of a neurodegenerative condition, and maybe that will point us in an initial direction. But the field is rapidly expanding with access to FDG-PET, amyloid PET, CSF biomarkers, genetic testing for APOE 4, probably soon to be serum biomarkers. So, patients may ask about this or a general neurologist referring to your clinic may ask, who should get these tests? When should we think about these tests? How do you think about when to send patients for advanced imaging, CSF biomarkers, genetic testing for APOE 4? Dr Day: It's not that patients may ask about this. Patients will ask about this. And you've probably experienced that in your own world as well. They're going to ask about any of these different biomarkers. Certainly, whatever they've recently read or has been covered on television is going to be common fodder for consideration in the clinic environment. It's important to know what tests you can get, what reliable tests that you can get, and to know the differences between some of these tests when making a recommendation or weighing the pros and cons of doing additional testing. I think common practice principles apply here. Let's order tests that are going to change our next steps in some way. And so, if we have a patient, particularly a patient like the one that we've been talking about: seventy something year old, presenting with memory complaints, they're concerned, the family is concerned. We've got that history, physical exam, and now we may need to really hone in on the etiology. Well, I say may need because for that patient it may be enough to know, yeah, I agree, there's a problem here. And I can say it's an amnestic, predominant, gradual-onset progressive cognitive decline. This is probably Alzheimer disease based on your age. And maybe that's all they want to hear. Maybe they're not ready to pursue additional testing or don't see the value or need for additional testing because it's not going to change their perspective on treatment. In that case, it's okay to apply an often underrated test, which is the test of time. Recognizing this is a patient I can follow. I can see them in six months or twelve months, depending on what your clinic schedule allows. If this is Alzheimer disease, I'm going to expect further gradual progression that may affirm the diagnosis. We can think about symptomatic therapies for a patient like that, perhaps Donepezil as an early, early medication that may help with symptoms somewhat and we can leave it at that for the time being. But there's many scenarios where that patient or the family member says, look, I really need to know. We really want this answer. And as you pointed out, there are good tests and increasingly good tests that we have access to.  Dr Berkowitz: Well, that's a very helpful overview of the landscape of more precise diagnostic testing for Alzheimer disease specifically and how you think about which tests to order and when based on your pretest probability and the patient 's candidacy for some of these new potential therapies. To close here, as you said, treatment is discussed in another podcast. There's another article in this issue. So, we won't get into that today. But let's say you have gotten to the end of the diagnostic journey here. You are now convinced the patient does have Alzheimer's disease. How do you present that diagnosis to the patient and their family? Dr Day: I think here we're going to recognize that different styles align with different patients and families, and certainly different clinicians are going to have different approaches. I do tend to take a pretty direct approach. By the time that patients are coming to see me, they've probably already seen another neurologist or at least another physician who's maybe started some of the testing, maybe even built the foundation towards this diagnosis and shared some indications. Certainly, when they look up my profile before they come to see me, they know what I specialize in and so, they may even have done their own research, which has ups and downs in terms of the questions that I'll be faced with at that point in time. The way I like to start is first acknowledging the symptoms. And the symptoms that the patients have shared with me, recognizing if those symptoms are impacting daily life, how they impacted daily life, and usually using that information to synthesize or qualify the diagnosis. Is there cognitive impairment, yes or no? And at what level is that cognitive impairment? Is this mild cognitive impairment? Is this mild dementia? Is it maybe more moderate or severe dementia? So, using those terms directly with patients and explaining the meaning of them. But I then transition in relatively quickly to the important point of not leaving it at the syndrome, but actually thinking about the cause. Because it is cause that patients come to talk about. And if they don't say that directly, they say it in their next question, which is what are we going to do about it and how are we going to treat this? And so, I will use the information I have available at that time to suggest that based on your age, based on the history, the normal physical examination, the performance and the bedside testing that we've done. And hey, that's pretty normal structural imaging or imaging that only shows a little bit of atrophy in a few areas. I think that this condition is most consistent with symptomatic Alzheimer's disease, mild cognitive impairment due to Alzheimer's disease, or mild dementia due to Alzheimer's disease. And then I'll discuss the next options in terms of testing and try to get a feel of what our patients are thinking about when it comes to treatment. Do they want to be on the cutting edge with brand-new therapies that offer potential benefits but counterbalance by pretty substantial risks that warrant individualized discussions? Are they interested in symptomatic therapies? Would that be appropriate for them? And I can usually round out the discussion with advice that works for everyone. And that's where we talk about the importance of brain health. What are the other things that I should be doing, you should be doing, and our patients and their partners should be doing as well to maintain our brain in its best possible state as we hope that we all continue to age and look towards the future where we maintain our cognition as best as possible? And that is still the goal. Even when we're talking to patients who have neurodegenerative diseases that are working against our efforts, we still want to do what we can to treat other problems, to evaluate for other problems that may be contributing to decline and may be amenable to our management as well.  Dr Berkowitz: Well, thank you so much for taking the time to speak with us today. I've learned a lot from your very nuanced and thoughtful approach to taking the history, performing the examination, making sense of cognitive tests and how they fit into the larger picture of the history and examination, and thinking about which patients might be candidates for more advanced imaging as we try to make a precise diagnosis in patients who may be candidates and interested in some of the potential novel therapies, which we both alluded to a few times, but are deferring to another podcast that we'll delve more deeply into that topic in this series. So, thank you so much again, Dr Day. Again, I've been interviewing Dr Gregory Day from the Mayo Clinic, whose article on Alzheimer's disease appears in the most recent issue of Continuum on Dementia. Be sure to check out Continuum Audio episodes from this and other issues. And thank you so much to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/AudioCME. Thank you for listening to Continuum Audio.

Credits: 0.25 AMA PRA Category 1 Credit™   CME/CE Information and Claim Credit: https://www.pri-med.com/online-education/podcast/frankly-speaking-cme-399 Overview: In this episode, we look at a new study showing increased probability of survival for patients with Alzheimer disease (AD) who take donepezil and memantine together. We review current treatments for AD and address common hesitations in prescribing dual pharmacotherapy, providing vital insights for primary care clinicians. Episode resource links: Yaghmaei, E., Lu, H., Ehwerhemuepha, L. et al. Combined use of Donepezil and Memantine increases the probability of five-year survival of Alzheimer's disease patients.Commun Med 4, 99 (2024). https://doi.org/10.1038/s43856-024-00527-6 Guo J, Wang Z, Liu R, Huang Y, Zhang N, Zhang R. Memantine, Donepezil, or Combination Therapy-What is the best therapy for Alzheimer's Disease? A Network Meta-Analysis. Brain Behav. 2020 Nov;10(11):e01831. doi: 10.1002/brb3.1831. Epub 2020 Sep 10. PMID: 32914577; PMCID: PMC7667299. Guest: Jillian Joseph, MPAS, PA-C Music Credit: Richard Onorato Thoughts? Suggestions? Email us at FranklySpeaking@pri-med.com   

Credits: 0.25 AMA PRA Category 1 Credit™   CME/CE Information and Claim Credit: https://www.pri-med.com/online-education/podcast/frankly-speaking-cme-399 Overview: In this episode, we look at a new study showing increased probability of survival for patients with Alzheimer disease (AD) who take donepezil and memantine together. We review current treatments for AD and address common hesitations in prescribing dual pharmacotherapy, providing vital insights for primary care clinicians. Episode resource links: Yaghmaei, E., Lu, H., Ehwerhemuepha, L. et al. Combined use of Donepezil and Memantine increases the probability of five-year survival of Alzheimer's disease patients.Commun Med 4, 99 (2024). https://doi.org/10.1038/s43856-024-00527-6 Guo J, Wang Z, Liu R, Huang Y, Zhang N, Zhang R. Memantine, Donepezil, or Combination Therapy-What is the best therapy for Alzheimer's Disease? A Network Meta-Analysis. Brain Behav. 2020 Nov;10(11):e01831. doi: 10.1002/brb3.1831. Epub 2020 Sep 10. PMID: 32914577; PMCID: PMC7667299. Guest: Jillian Joseph, MPAS, PA-C Music Credit: Richard Onorato Thoughts? Suggestions? Email us at FranklySpeaking@pri-med.com   

On this episode of the Real Life Pharmacology podcast, I cover medications 51-55. They are eszopiclone, celecoxib, estrogen, moxifloxacin, and donepezil. Eszopiclone is a "Z" drug used for insomnia. Its adverse effect profile is very similar to benzodiazepines. Celecoxib is a COX-2 Inhibitor used for pain and inflammation. I discuss how this medication differs from traditional NSAIDs. Estrogen therapy is used for menopausal symptoms but carries a risk of cancer and blood clots. Moxifloxacin is a quinolone antibiotic. Binding drug interactions, boxed warnings, and QTc prolongation are potential concerns. Donepezil is a medication used for dementia. I discuss its mechanism of action and common adverse effects.

Study Shows Ginkgo Biloba Improved Memory As Well As Donepezil Without The Side Effects Dr. Steve Blake • http://www.drsteveblake.com • Book – Nutrients for Memory #SteveBlake #AlternativeMedicine #AlzheimersDisease Dr. Steve Blake, ScD is a doctor of science specializing in nutritional biochemistry. He is Director of Nutritional Neuroscience at the Maui Memory Clinic. He is lead advisor and author for the Macmillan Reference, Gale Encyclopedia of Alternative Medicine. He has worked as Faculty Nutritional Biochemist at Hawaii Pacific Neuroscience for years. He is a research scientist who just finished a clinical study at the Hawaii Alzheimer's Disease Center that he designed and ran with a large team.  He is research director at the Neuroscience Nutrition Foundation. He has presented grand rounds at John A. Burns School of Medicine at U.H., Castle Medical Center in Kailua, Hawaii, Hawaii Pacific Neuroscience, St. Francis Liliha, Honolulu, and at Boston University Medical Center. He is author of Nutrients for Memory, Fats and Oils Demystified, the McGraw-Hill college textbook Vitamins and Minerals Demystified, Stop Strokes Before they Start, Autism: A Spectrum of Improvement, Mastering Migraines: Prevention and Relief, Arthritis Relief, Parkinson's Disease: Dietary Regulation of Dopamine, Healing Medicine, A Nutritional Approach to Alzheimer's Disease, No More Heart Attacks, Mosby's Alternative Remedies, and co-author of Mosby's Drug Guide for Nurses, 4th edition. Steve Blake has taught twenty-five classes at the University of Hawaii on Maui. He has taught classes at Stanford University, McLean's Harvard Teaching Hospital, and at Boston University Medical Center. As a professional, registered medical plant specialist, he is well known for his databases on alternative remedies. The Herb Doctors database has information from 54 countries and regions worldwide and has over 168,000 footnoted facts. This database was also published by Mosby as Alternative Remedies. Steve Blake programmed the Diet Doctor, software for graphing dietary nutrients. This cutting-edge research software has been instrumental in revealing nutrition information. Steve Blake lectures widely about the role of nutrition in health. He has taught anatomy & physiology and exercise physiology. He was the director of the Maui Holistic Health Center for seven years. He is often heard on radio and seen on television. He attended the University of California at Berkeley. Steve Blake has a doctorate in holistic health specializing in nutritional biochemistry. He also has a doctorate in naturopathic medicine and is a neuromuscular therapist.  He and his wife Catherine live on an organic farm on Maui that is powered by the sun. To Contact Dr Steve Blake go to drsteveblake.com Disclaimer:Medical and Health information changes constantly. Therefore, the information provided in this podcast should not be considered current, complete, or exhaustive. Reliance on any information provided in this podcast is solely at your own risk. The Real Truth About Health does not recommend or endorse any specific tests, products, procedures, or opinions referenced in the following podcasts, nor does it exercise any authority or editorial control over that material. The Real Truth About Health provides a forum for discussion of public health issues. The views and opinions of our panelists do not necessarily reflect those of The Real Truth About Health and are provided by those panelists in their individual capacities. The Real Truth About Health has not reviewed or evaluated those statements or claims. 

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay.In today's episode I will be setting up the verbal conference about drug details, all reversible anticholinesterases like Physostigmine, Neostigmine, Pyridostigmine, Rivastigmine, Galantamine, Edrophonium, Ambenonium, Distigmine, Tacrine, Donepezil....All sea waters gonna be touched and splashed like basic characteristics, derivation, chemical nature, half life, pharmacodynamics, pharmacokinetics, and as the discussion proceeds, drugs will be compared and evaluated as per their pros and cons too!All in all , a good thorough knowledge storm filling up the sky of curiosity and learning!!Are you ready, if yes, its your cup of tea, if you do not find it, it is advised that stay tuned and soon it gonna be in your cup :)For all the updates and latest episodes of my podcast, please visit-  www.ispharmacologydifficult.com  where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also.You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!!You can access various links via- https://linktr.ee/ispharmacologydifficult

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay. In today's episode I will be setting up the verbal conference about drug details, all reversible anticholinesterases like Physostigmine, Neostigmine, Pyridostigmine, Rivastigmine, Galantamine, Edrophonium, Ambenonium, Distigmine, Tacrine, Donepezil.... All sea waters gonna be touched and splashed like basic characteristics, derivation, chemical nature, half life, pharmacodynamics, pharmacokinetics, and as the discussion proceeds, drugs will be compared and evaluated as per their pros and cons too! All in all , a good thorough knowledge storm filling up the sky of curiosity and learning!! Are you ready, if yes, its your cup of tea, if you do not find it, it is advised that stay tuned and soon it gonna be in your cup :) For all the updates and latest episodes of my podcast, please visit- www.ispharmacologydifficult.com where you can also sign up for a free monthly newsletter of mine. It actually contains lot of updates about the medical sciences, drug information and my podcast updates also. You can follow me on different social media handles like twitter, insta, facebook and linkedin. They all are with same name "IS PHARMACOLOGY DIFFICULT". If you are listening for the first time, do follow me here, whatever platform you are consuming this episode, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe, stay happy, stay enlightened, Thank you!! You can access various links via- https://linktr.ee/ispharmacologydifficult

Folge 64: Corona-Bonus für PTA, CBD und Rote Hand zu Donepezil

Dementia is a general term for loss of memory, language, problem-solving, and other thinking abilities that are severe enough to interfere with daily life. Alzheimer's is the most common cause of dementia.As life expectancies increase, more and more people are at risk of developing dementia. But what does it even mean?According to alz.org, in the United States, there are more deaths from Alzheimer's and dementia than from breast cancer and prostate cancer combined. In the past few years, Alzheimer's deaths have increased by 16%. In 2021, Alzheimer's will cost the nation $355 billion. By 2050, this number could be over $1 trillion. More than 11 million Americans take care of people with Alzheimer's or other dementias without getting paid for it.Join me and Dr. Jason Karlawish as we chat about how you need to prepared for the increase in cases of dementia. We talked about how often people are getting dementia. 100 years ago, people did not get it as much and the cases were not diagnosed. They were not dying from it as often. Now, there are more cases of Alzheimer's than before. What would you do if you went back in time and talked to someone with memory problems? If the person has problems early on in life, they can be diagnosed with Alzheimer's. To help them, we need policy changes that will improve the well-being and dignity of people living with dementia.--------------------Timestamps:[00:00] Pre-intro dialogue from Jason Karlawish[01:41] Friendly get to know you and Hanh's experience with dementia in her family.[04:05] Introduction to Jason Karlawish[04:46] Jason's background, including what exactly sparked his interest in Alzheimer's and Dementia?[06:06] It seems like a hundred years ago, people didn't die of Alzheimer's as often. Was it just underdiagnosis or something else?[09:36] If you could go back a hundred years, what would you do to educate people about Alzheimer's to prevent us from being in the place where we are today?[11:25] How are we able to diagnose Alzheimer's early, even before a person has any memory problems?[14:40] Things we can do now to prepare for the future increase in cases of dementia?[17:41] What effect does a negative stigma around memory loss and dementia have on those with dementia?[19:20] Ageism and its role in these stigmas?[19:38] What could we do to break down these stereotypes? On a personal level and cultural level?[23:42] Your thoughts on Biogen's new drug?[25:19] Why are some people confused about the moral aspects of Alzheimer's medication?[27:06] Thoughts on future success as an Alzheimer's medication?[28:45] Ways to improve Alzheimer's disease treatment today without using drugs like Biogen's, returning to old treatments, such as HRT or Donepezil?[31:45] Implications social media have for our sense of determination in a society?[33:02] Anything else that you would like to add?[34:49] Where can listeners find you and find your book?--------------------Bio:Dr. Jason Karlawish is a physician and writer who researches and writes about issues at the intersection of bioethics, aging, and the neurosciences. Dr. Karlawish's work has aired on NPR (National Public Radio) as well as The New York Times, Washington Post, Forbes, Philadelphia Inquirer, and many others. His book "The Problem of Alzheimer's" will be published February 2021 by Macmillan/St Martin's Press in association with TED Books; this book tells the story of how science culture politics turned a rare disease into a crisis that we can do something about!Find out more about Jason:LinkedIn: https://www.linkedin.com/in/jason-karlawish-a4888030/Website: https://www.jasonkarlawish.com/

Un nouvel épisode du Pharmascope est maintenant disponible et on termine notre série d'épisodes sur les troubles neurocognitifs majeurs. Dans ce 76ème épisode, Nicolas, Sébastien, Isabelle et leur invité discutent du traitement pharmacologique de la démence.  Les objectifs pour cet épisode sont: Expliquer les bénéfices et les risques associés aux traitements pharmacologiques des troubles neurocognitifsDiscuter du suivi de l'efficacité et de l'innocuité des traitements utilisés dans les troubles neurocognitifsComparer les avantages et inconvénients des différents agents utilisés dans le traitement des troubles neurocognitifs Ressources pertinentes en lien avec l'épisode Revues systématiquesBirks JS, Harvey RJ. Donepezil for dementia due to Alzheimer's disease. Cochrane Database Syst Rev. 2018;6:CD001190. Birks JS, Evans JG. Rivastigmine for Alzheimer's disease. Cochrane Database Syst Rev. 2015;4:CD001191. McShane R et coll. Memantine for dementia. Cochrane Database Syst Rev. 2019;3:CD003154. Consensus canadien sur la démenceIsmail Z et coll. Recommendations of the 5th Canadian Consensus Conference on the diagnosis and treatment of dementia. Alzheimers Dement. 2020;16:1182-95. Commission du LancetLivingston G et coll. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020;396:413-46. Documents de l'INESSSInstitut national d'excellence en santé et en services sociaux. Outils de repérage mesurant les fonctions cognitives, l'autonomie fonctionnelle et les symptômes comportementaux et psychologiques de la démence. 2015. Institut national d'excellence en santé et en services sociaux. Alzheimer - outils / activités. 2015.

Can you combine donepezil with antidepressants in later-life depression? What are the benefits? What is the downside? Faculty: Charles F. Reynolds III, M.D. Hosts: Jessica Diaz, M.D.; Flavio Guzman, M.D. Learn more about Premium Membership here Earn 1 CME: Evidence-Based Treatment of Major Depressive Episodes in Later Life Long-Term Treatment in Later- Life Depression: Maintenance, Adverse Effects, and Combination of Antidepressants and Donepezil

Early onset Alzheimer’s can be an enormously difficult diagnosis to come to terms with. Many people who are diagnosed are in the middle of a career, raising a family, and pursuing new ventures when this disease unexpectedly disrupts life as they know it.   New studies have found that an early diagnosis could lead to more positive experiences with treatment and there are ways to slow the rate of progression so patients can maintain a sense of normalcy for as long as possible.   Still, there is no cure for Alzheimer’s disease, so anyone who has received a diagnosis will have to re-evaluate many things in their life in order to best prepare for what’s to come.   On today’s episode of All Home Care Matters, we’ll be discussing all you need to know about early onset Alzheimer’s. We know how difficult this disease can be to face – so we want you to know that we are here to support you through the ups and downs of this new and trying journey.   This episode will be a little different. In addition to discussing what early onset Alzheimer’s is and how it affects the brain, what symptoms to look for and what options are for treatment, we’ll also talk about the tougher stuff. How to speak to your kids about a diagnosis. How to handle friends, family, and a possible stigma that you might face outside of your home. How to plan ahead financially and legally, while you’re still in the early stages of the disease.   We know that this is a diagnosis that interrupts your world. That’s why it’s so important to take the time to prepare for the future and implement a healthy lifestyle with a treatment plan. That way, you can focus on spending time with your family and taking on new and cherished experiences, instead of spending all of your time worrying and stuck in the dark about what comes next.   Many people with early on-set Alzheimer’s feel alone after a diagnosis. Watching friends and family continuing to live their lives, getting to focus solely on their careers and family, can cause a great deal of resentment and even depression.   One key difference, on an emotional level, between Alzheimer’s and early onset Alzheimer’s is that those experiencing the former are more likely to have peers in similar situations – whether friends, friends of friends, or a community in a senior living facility. For those with early onset, the world can feel like it’s coming to a halt for you and only you.   That’s why I want to start by saying this: even though it may not feel like it now, you are not alone. According to alz.org, it’s estimated that about 200,000 people in the United States have early onset. That’s 5% of the 5 million Americans living with Alzheimer’s.    If you are at all interested, in can be enormously helpful to meet others who are facing similar circumstances. There are support groups available for patients with the diagnosis as well as counseling services, gathering events, and more. Look into your local community to see what resources might be available to you. Surrounding yourself with others who know what you are going through could help you to feel supported, encouraged, and not alone.   Now, before we get any further, let’s get into the basics. When anyone under the age of 65 is diagnosed with Alzheimer’s disease, it’s considered early onset, or younger onset. A person can be in their thirties, forties, or fifties. More rarely, a person might get the disease as early as their twenties.   In the brain, early onset does not look different from standard Alzheimer’s. In both cases, the brain is no longer able to function normally because of nerve cell death and tissue loss caused by a build-up of protein fragment clusters between nerve cells. At the same time, a dead nerve cell contains tangles – or twisted protein strands.   The protein fragment clusters are known as plaques. When the plaques and tangles crowd the brain together, it caused mixed-up signaling that can trigger immune system cells, which consume the dead or dying cells and trigger inflammation.   In the end, the brain is unable to properly process nutrients or other important supplies. That leads to cell death. The dead cells tend to crowd in the areas of the brain that affect thinking, planning, learning, and memory. That’s why Alzheimer’s patients eventually lose their memory altogether. To learn more about how Alzheimer’s affects the brain, check out our episode on understanding Alzheimer’s and dementia.   While it is estimated that around 200,000 Americans are living with early onset, that number is likely even greater. The disease is often overlooked or misdiagnosed by doctors, who simply do not consider Alzheimer’s or dementia on their younger patients. Sometimes, a patient can get multiple misdiagnoses from multiple doctors before being diagnosed with early onset. This means that many people do not know they have the disease until they are already in the later stages.   If you believe you may have the disease, receiving a diagnosis can be a painful and disheartening process. That’s why it’s so important to advocate for yourself and push your doctors to evaluate you for early onset if you are suffering from memory problems.   If you are truly worried and your doctor is simply not considering early onset even after you specifically ask, make an appointment with an Alzheimer’s specialist. They are much more likely to give you comprehensive, conclusive evaluation. At the very least, they will help you to feel validated and comforted – which can mean the world after enough doctor appointments that felt like they were going nowhere.   It’s important to note that early onset is not something you can take a test for like strep throat or the flu. It can only be diagnosed after a careful and drawn-out medical evaluation, in which the doctor will ask you a series of questions about your symptoms, memory, and quality of life, before making a definite diagnosis. Remember to be honest with your answers and share anything memory related, even if you feel it isn’t relevant, because too much information is always better than not enough – especially when going after a diagnosis that is difficult to come by at a younger age.   There are two types of early onset Alzheimer’s. The first type is Common Alzheimer’s Disease, which is the most typical form among both early onset patients and patients 65 and older. This version of the disease progresses at much the same rate in younger patients as it does in older ones. Unfortunately, researchers have not yet determined what causes Common Alzheimer’s Disease, and there are no risk factors that might lead to the disease. Common Alzheimer’s early onset could happen to anyone.   The other type is early onset familial Alzheimer disease. This is much rarer. Patients with this type of Alzheimer’s usually have a parent or parents that have also had the disease. A patient’s siblings and children have a 50/50 chance of getting the disease themselves at an atypically young age. A person who has two parents with the disease is at a higher risk than someone who only has one parent with it.   Researchers have pinpointed two types of genes that influence a person’s likelihood to get familial Alzheimer’s disease. These are risk genes and deterministic genes.   If a person has risk genes, then they have an increased chance of developing the disease, but it is not guaranteed. Risk genes include APOE-e4, APOE-e2, and APOE-e3. Those with APOE-e4 have a 40-65% chance of eventually being diagnosed with Alzheimer’s. According to alz.org, about 2% of the US population has this gene.   Deterministic genes guarantee that a person will inherit Alzheimer’s. This type of gene is exceptionally rare – only a few hundred families have been found to pass it on worldwide. Deterministic genes lead to early onset Alzheimer’s for patients in the early 40’s to mid 50’s.   Sadly, early onset cases tend to progress more quickly than standard Alzheimer’s in older patients. This is because in patients with early onset, the plaque and tangle build up tends to be much larger. Alzheimer’s expert Dr. Thomas Wisniewski explained to CBS news in 2016 that, “the pathology tends to be more extreme in early-onset. Many can deteriorate more quickly, so it is a much more aggressive disease…when you look at the pathology, it’s just like late-onset Alzheimer’s disease, but there’s just more of it.”   This is the often-brutal reality for patients facing the early-onset form of this disease. However, because recent studies have found that early diagnosis can lead to better treatment options and a longer delay of progression, it’s essential that patients look for symptoms and report them to a doctor as soon as they notice any.   This is especially true for people whose parents or siblings have had Alzheimer’s or early-onset, but it is also true for anyone else, since there is no known cause for the majority of these cases.   Symptoms of early onset are quite similar to other versions of the disease. They include forgetting newly learned information, important dates, and even names of people close to them. If a person asks for information to be repeated multiple times on a semi-regular basis, this could be a sign. If a person is failing to remember something they used to know by heart – like a favorite recipe, hobby, or craft that they should be able to do with their eyes closed – that’s another sign. If a person is forgetting to pay their bills or stay on top of other important responsibilities, and gets confused and overwhelmed when they try, this is another sign.   Other symptoms include wandering or getting lost, forgetting how you got from one place to another, losing track of dates, forgetting important events, having trouble socializing, struggling to remember certain words in conversation, vision issues or depth perception issues, poor judgement, and slight mood and personality changes. In the later stages, symptoms include major mood swings and drastic changes to personality, increased paranoia – particularly surrounding close friends, family members, and caregivers – difficulty speaking and swallowing, mobility issues, and severe loss of memory.    If any number of these symptoms sound like you – don’t wait to book an appointment with an Alzheimer’s specialist. Again, the sooner you can get diagnosed, the better your options for treatment will be. Early diagnosis really is crucial to maintaining a normal quality of life for as long as possible.   While early onset Alzheimer’s does not have a cure, there are treatment options that can slow the progression of the disease and help patients maintain a good quality of life for longer than if no treatment was implemented.   Treatments usually consist of a mixture between medicines, physical activity, and healthy living. Common prescribed medications are Donepezil, Rivastigmine, Galantamine, and Memantine. Medicines can help a person for as long as months or even years, especially when combined with lifestyle changes.   Healthy lifestyle choices for patients with early onset are quite similar to those with standard Alzheimer’s disease. This means making a consistent effort to care for your physical, mental, and emotional wellbeing.   Alz.org recommends that patients find a physician that they truly trust and then build a relationship with them through regular check-ups. When your doctor is intimately familiar with your case, they will be more likely to notice any changes, even the subtle ones, that might require a change in treatment plan. At the same time, the more you trust your doctor, the more likely you are to call when you need guidance or have a medical related question.   You need to come up with a diet and exercise routine that will keep you moving, alert, and energized. The healthier and stronger your body is, the better equipped your mind will be to delay the progression of this disease. You can work with your doctor to establish a diet and exercise plan that best fits your individual needs.   There are also nutritionists, physical therapists, and personal trainers who specialize in Alzheimer’s patients. Be sure to work closely with an expert so you know that you are not over or under working yourself, and you are staying as healthy as possible.   All Alzheimer’s patients should drink less alcohol and more water and eat more fruits and vegetables and less junk food. When it comes to exercise, it’s usually recommended that patients engage in mild-to-moderate routines that will increase endorphins and help the body and mind without over-exerting the patient. According to alz.org, “physical activity may help delay or slow decline in thinking skills, reduce stress, possibly improve symptoms of depression, and may even reduce the risk of falls. Some evidence also suggests that exercise may directly benefit brain cells by increasing blood and oxygen flow. Even stronger evidence suggests exercise may protect brain health through its proven benefits to the cardiovascular system.”   The same site recommends trying exercises like aerobics, walking, biking, tennis, or even walking. Remember to consult your medical team before you engage in any exercise, though, because they will best know what you are capable of and what might help you the most.   In addition to diet and exercise, mental stimulation can play a big role in strengthening your brain and slowing cognitive decline. Try taking a class, picking up a new hobby, playing board games, or reading. Anything to stimulate your brain and get you thinking and problem solving is beneficial.   You also need to care for yourself emotionally. This is a diagnosis that can be devastating to live with, especially when you’re in the prime of your life, raising kids and engaging in a career. Early onset patients are liable to depression, anxiety, mood swings, and extreme feelings of loneliness. While you should certainly give yourself permission to feel whatever you need to during this difficult time, it is important to note that depression can actually lead to bigger health issues and even quicken the progression of your disease.   To help with these feelings, you have many options. You can join a support group for other patients with early onset so you can be part of a community that understands what you are going through. You can meet with a counselor or therapist regularly – especially one that specializes in Alzheimer’s and dementia. You can take time every day to do something you love, just for you. You can spend more time outside on walks, exercising, or just enjoying the fresh air. You can meet with trusted friends and family members and confide your fears and worries to them.   Early onset Alzheimer’s can hit so much harder when you are a parent in the middle of raising a family. Many early onset patients are young mothers and fathers who have to grapple with what their diagnosis will mean for their family. For some, this is the scariest part. No parent wants their child to go through grief, loss, or heartache of any kind – and to know that this disease will affect them can feel devastating. At the same time, many parents are left wondering if they will miss important milestones in their children’s lives or be able to be there for them as they grow up. Harboring these fears is a terrible thing for any parent to go through.   By caring for your physical and emotional needs, you will more likely be in a better place to care for your children longer and stay strong for them when you want to be. As hard as it might feel, do not neglect your own needs. The more you care for yourself, the better equipped you’ll be to care for your children.   Whether or not to talk to your child about your diagnosis will depend on a variety of factors – but ultimately, the decision is a deeply personal one that can only be made by you. How much you share might depend on your child’s age and what they are capable of digesting and understanding.   Children and teenagers alike might respond with a myriad of emotions. These can range from confusion, sadness, anger, curiosity, worry, guilt, embarrassment, or even jealousy as they are having to share their attention with their struggling parent. Teenagers in particular might withdraw from family and friends, have a hard time in school, stay away from home because it is too hard to see their parent suffer, avoid inviting friends over, and easily jump to anger or even aggression.   Remember that your child or teenager is grieving. This diagnosis means a loss of the way life used to be – and it is extremely heart wrenching for most children to watch their parents change and decline. Be patient with your child and give them space to feel how they need to.   There are many ways you can help your child to cope with this diagnosis and their changing lives. Offering patience, love, and support can mean everything. When your child knows they can go to you or their other parent or caretaker with their questions and their big feelings, then they are less likely to seek an outlet elsewhere.   It might help to arrange therapy or counseling for your child, or even group therapy for other kids who are going through the same thing. Just as building your own community is so beneficial, it will make children feel far less alone to know others can relate to them.   Provide your children with a space for their feelings – whether through art, music, or journaling. Educate them about the disease and what they can expect as time goes on, so they are not taken by surprise as the condition worsens. Be open and honest with them.   Family activities can also be enormously helpful, as they allow a child or teenager to hold onto a sense of family and stability – so they feel less lost and scared that they are losing their foundation. Activities can include walking, hiking, going to movies, playing or listening to music, playing board games. You can look through family photo albums together, read together, even do housework together. The more routine family time can be, the better.   In the description of this episode, you’ll find further resources that can help you navigate parenthood with your new diagnosis. These include a list of common questions and answers, activity ideas, and advice for getting through those tough conversations.   In addition to parenthood, you might be struggling with stigma from family and friends. Because early onset is so uncommon, you might find that those around you are getting impatient with you or acting frustrated when you are unable to do things as fast or as easily as you used to. To help with this stigma, make sure to educate your loved ones about your disease. Provide them with resources that will help them to understand what you are going through and what they can expect in the months and years ahead. You can even arrange a meeting with your care team and your loved ones, to answer any of their questions and explain your individual situation on a deeper level.   In the early stages of the disease, it’s essential to plan ahead for the future. This means legal and financial planning, so your family is not left confused and lost when they need this information later on.   You will likely feel daunted and overwhelmed when it comes to legal planning – so don’t be afraid to enlist the help of friends, family, and a lawyer to make sure that everything is taken care of and you are not having to carry this weight on your own.   Begin by organizing all important legal documents to your name, making necessary updates, and putting a plan in place for future finances for your healthcare, long-term care, and will. Give someone you trust power of attorney for when you are no longer to make legal decisions. A person with power of attorney will be able to make decisions for you and sign for you on important documents. Make sure that this person is fully aware of everything you want and need for the future, so they can make sure to make decisions based on your own plans and hopes.   Financial planning will include organizing documents and checking over your assets and debts, so you know exactly what you are responsible for down the road. Choose a family member, or family members, to help you with your financial plans when you are no longer able to. This person should have intimate knowledge about your finances and have your best interests in mind and in heart.   Find out the care options available to you and what they might cost. Whether you choose a family caregiver, hired home care, a nursing home, memory home, or assisted living facility will depend on what you can afford and what you desire. Check your insurance and benefits. Patients with early onset Alzheimer’s disease will be eligible for Medicaid. You might also have long-term care insurance, life insurance, or other health insurance that can help you pay for care costs. If you are still working, see if your employer has any disability or early retirement benefits that might help you.   It is recommended that people with memory issues stay in familiar surroundings, as strange places can quicken the progression of the disease. To learn more about choosing the right care, listen to our episodes on Alzheimer’s, dementia, and long-term care options.   Early onset dementia is an extremely difficult diagnosis for anyone to face. The more you can prepare for the road ahead, though, the more you can focus on spending precious time with your friends and family and doing what you love, instead of worrying about an uncertain future. Start planning today for the road ahead.   We want to thank you for joining us here at All Home Care Matters, All Home Care Matters is here for you and to help families as they navigate long-term care issues. Please visit us at allhomecarematters.com there is a private secure fillable form there where you can give us feedback, show ideas, or if you have questions. Every form is read and responded to. If you know someone is who could benefit from this episode, please share it with them. Remember, you can listen to the show on any of your favorite podcast streaming platforms and watch the show on our YouTube channel and make sure to hit that subscribe button, so you'll never miss an episode. On our next episode we will be welcoming several guests who will be sharing how they have remained engaged, active, and building friendships and socializing while quarantining during covid. This is an interview you won’t want to miss!   Here are the resources used for this episode:   https://www.alz.org/help-support/i-have-alz/younger-onset   https://www.alz.org/alzheimers-dementia/what-is-alzheimers/younger-early-onset   https://www.alz.org/alzheimers-dementia/what-is-alzheimers/causes-and-risk-factors/genetics   https://www.alz.org/help-support/i-have-alz/live-well/taking-care-of-yourself   https://www.alz.org/help-support/resources/kids-teens/for_parents_teachers   https://www.alz.org/help-support/i-have-alz/plan-for-your-future/financial_planning   https://www.alz.org/help-support/i-have-alz/plan-for-your-future/financial_planning   https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers/art-20048356   https://www.hopkinsmedicine.org/health/conditions-and-diseases/alzheimers-disease/earlyonset-alzheimer-disease   https://memory.ucsf.edu/genetics/familial-alzheimer-disease   https://rarediseases.info.nih.gov/diseases/632/familial-alzheimer-disease   https://www.cbsnews.com/news/pat-summitts-death-what-to-know-about-early-onset-alzheimers/          

Can you believe this is our 100th episode??? It has been a little over 6 months since our official launch and we are now running full steam, thanks to a hardworking team. Cheers to the members of AMiNDR, and cheers to you for listening to us. This episode is for those of you who are interested in what's already on the marker for treating Alzheimer's diseases. That's right, you have knowingly or by chance stumbled upon our episode on refining or repurposing existing medications, as well as improving methods of drug delivery. You will hear about advances in refining the use of Memantine, Donepezil, and Rivastigmine, and exploring the potential of drugs like Lithium, Escitalopram, or Sildenafil to alleviate the symptoms of AD. We also cover papers that look at refining methods of drug delivery, efficiency, or bioavailability. Sections in this episode:  Section 1: Refining existing drugs 3.53 Memantine (1 paper): 4.26 Donepezil (3 papers): 6.03 Rivastigmine (1 paper): 12.55 Section 2: Refining methods (delivery, efficiency, bioavailability): (5 papers) 15.25 Section 3: Repurposing approved drugs (6 papers): 28.26 Bonus paper: 43.29 ------------------------------------------------------------------ To receive the list of papers covered, please fill this form:  -------->  https://forms.gle/CVVbznAFM8pamdgk6  -------  or by tweeting at us: @AMiNDR_podcast  ------------------------------------------------------------------ We would appreciate your feedback so we can better cater to your needs.  You can fill our feedback form here  ---------->  https://forms.gle/5aq2JyrT6g4P1m8v6  You can also share your thoughts and suggestions by contacting us:  Email: amindrpodcast@gmail.com  Facebook:  AMiNDR  Twitter: @AMiNDR_podcastInstagram: @AMiNDR.podcast------------------------------------------------------------------ Today's episode was scripted by Sarah Louadi and Naila Kuhlmann, reviewed by Joseph Liang, and hosted and edited by Sarah Louadi. All of this was made possible thanks to an entire team of volunteers behind the scenes.  Our music is from "Journey of a Neurotransmitter" by musician and fellow neuroscientist Anusha Kamesh; you can find the original piece and her other music on soundcloud under Anusha Kamesh or on her YouTube channel, AKMusic.  https://www.youtube.com/channel/UCMH7chrAdtCUZuGia16FR4w  ------------------------------------------------------------------ If you are interested in joining the team, send us your CV by email. We are specifically looking for help with abstract summary and podcast editing. However, if you are interested in helping in other ways, don't hesitate to apply anyways.  ------------------------------------------------------------------ *About AMiNDR: *  Learn more about this project and the team behind it by listening to our first episode: "Welcome to AMiNDR!"

Donepezil

Caregivers can spot dementia in numerous ways, ranging from a loved one forgetting about their favorite television program to suddenly not remembering to pay their bills on time. Learn who Dr. Cesar Torres says is most at risk of dementia and how to manage it.   TRANSCRIPT Intro: MedStar Washington Hospital Center presents Medical Intel where our healthcare team shares health and wellness insights and gives you the inside story on advances in medicine. Host: We’re speaking with Dr. Cesar Torres, a geriatric and house-call doctor at MedStar Washington Hospital Center. Thank you for joining us, Dr. Torres. Dr. Torres: Good afternoon. Host: Today we’re discussing dementia, a neurological condition that tends to develop in older adults and is characterized by memory loss and confusion. Dr. Torres, could you start by discussing how dementia develops in the brain? Dr. Torres: Certainly. Dementia develops as a result of the production of a neurotoxic protein called beta amyloid and, as a result of accumulation of this protein, nerve cells in certain areas start to die, specifically the memory centers of the brain - the hippocampus, the parietal lobe - and, as a result, people start to experience neurocognitive deficits. The most dramatic ones tend to be in the memory realm, but there are other cognitive deficits that also develop. And these eventually lead to significant social dysfunction and impairment, and it’s, unfortunately, very progressive. Host: Are there any populations of people who are at increased risk for dementia? Dr. Torres: Well, the number one risk factor for dementia is age. The older you are, the higher the prevalence. Recent estimates - generally, by the time you’re 70-75, there’s upwards of a 20 percent prevalence rate. Dementia encompasses a few different pathologies. There’s Alzheimer’s dementia, there’s Vascular dementia, there is a dementia associated with Parkinson’s, there’s a Lewy body dementia and there are some other much more esoteric subtypes. The vast majority are Alzheimer’s-type dementia, generally in the range of 60, 70 percent. After that, Vascular dementia rounds off the list, mostly around 15 to nearly 20 percent. And then, all the others. So, each one tends to have certain predispositions. For Alzheimer’s, there’s a genetic predisposition. It’s not 100 percent correlative, but there is a genetic predisposition and it can run in families. Vascular dementia tends to affect folks who have vascular disease - hypertension, coronary artery disease, people who are more prone to strokes. Brain trauma can predispose people to another subtype of dementia, and there’s a lot of focus now on this Traumatic encephalopathy that we see in a lot of professional, high-contact sports. Some of the other more esoteric subtypes - probably more of a genetic predisposition. So, as far as high-risk groups are concerned, that’s not an all inclusive list but there are certain groups that are at greater risk. But like I said, age is the number one risk factor. So, if people could stop growing old, we wouldn’t have a problem. Host: In these high-risk individuals and these aging individuals, what are some of the warning signs of dementia that families should start watching for? Dr. Torres: That’s a very good question and unfortunately, it’s also a very broad question. Generally, the onset of Alzheimer’s tends to be extremely subtle. You’ll tend to see problems with the acquisition of new knowledge or new information, the retention of new knowledge and new information. A family member asks how to get to a grocery store over and over again, in spite of having been there not too recently. You can see difficulty with social functioning as well, as the disease progresses. An individual who was extremely capable of managing their finances suddenly forgets to pay their bills and the electricity gets turned off. As things progress, now you can see personality changes. Sometimes the person starts to retreat into themselves - more withdrawn as some awareness of the social dysfunction starts to creep into their consciousness. Generally, the family will feel something isn’t quite right with their loved one and that’s when they actually probably bring it to the attention of their primary care physician or caregiver. The social functioning piece becomes more dramatic and is more distressing for folks, and they tend to pick up on that fairly quickly because it’s a dramatic departure from previous level of functioning. Host: If someone notices that a loved one is showing signs of dementia, where should they turn for help? Dr. Torres: Generally, most primary care physicians can do at least the initial screening. This generally can include blood tests, neuro imaging - in the form of a CT scan or an MRI. There are some blood tests that can also help rule out reversible causes of memory loss. But generally, the primary care physician should be the first point of contact. Host: Are there any treatment options available to help patients with dementia manage their symptoms or reverse the condition? Dr. Torres: Well, unfortunately, we have no way to reverse it at the current time. And that’s the Holy Grail. There have been many, many, many attempts to find drugs and various treatments but none have really been successful up to this point. As far as medications to modify the progression of the disease, there are a few, the most famous one being Donepezil, trade name Aricept and Namenda, generic Memantine. If  you make a diagnosis of dementia, you don’t automatically use the medication. It’s best to have a conversation with the patient and the family and to decide whether or not the patient has reached the stage where they would benefit from this medication because all of these medicines has toxicity. What the medicines offer, really, are slowing the progression. And, you may see unfortunately temporary improvements in certain memory functions. But, unfortunately, over time, the effect diminishes and the disease starts to progress again. If you look at it on a bell curve, most folks will fall in the middle. They will get some, but there are those who can get a lot and there are some who, unfortunately, don’t get anything. The middle is where the bulk of the patients will fall. But on an individual, case by case basis, you can get a substantial amount of improvement. The biggest benefit, I feel, from starting treatment with these medications is time. You buy time. And time is very precious for people. So, on the basis of that, if we’re at a relatively early enough stage, I think it’s a worthwhile choice. Host: You mentioned a couple of different potential causes for dementia. What can patients do to reduce their risk of developing it? Dr. Torres: We have looked at lots and lots of different options - herbal medications, anti-inflammatories, Vitamin E - and the list goes on. But, to date, the only two things that I can recommend honestly? A healthy lifestyle and daily exercise. Daily exercise actually has evidence behind it. So, among all the other benefits that a person can obtain from daily exercise, prevention of dementia is another one. There was a sub-analysis of the Women’s Health Initiative Study that was done a few years ago that looked at the impact of exercise and noted that it reduced their relative risk by about 40 percent, as a result of daily cardiovascular exercise. The reasons for that, the mechanism behind it - still remains a bit unclear but I suspect it has to do with just overall benefits of exercise and physical activity. And it doesn’t need strenuous exercise also, but some form of daily cardiovascular exercise would be a great benefit. Well, I would recommend being very judicious with alcohol intake. There is an Alcoholic dementia that exists. Otherwise, avoiding smoking. Smoking can lead to vascular problems that can lead to Vascular dementia. Good sleep, weight control - things like that. Host: How do the dementia experts in the geriatrics program and the house-call program at MedStar Washington Hospital Center help patients and families achieve optimal outcomes? Dr. Torres: The number one way is in the diagnosis of the condition because sometimes it can present atypically. Sometimes it can present, as I said, very subtly. So, sometimes it has to be teased out. And again, it’s time. We can gain time for better interactions, more complete interactions with the patient and the family member. And there are a few conditions that can masquerade like dementia that we can treat and reverse the symptoms that we associate with dementia - the memory loss. The one that is most well known is depression. Depression can manifest itself as a type of dementia with memory loss, with loss of concentration, with apathy, as well. And so by treating that, the patient -- effectively treating that -- the patient can regain their function and their memory. Host: Could you give us an example of how you care for a dementia patient through the house-call program? Dr. Torres: Well, we have a very focussed approach with really educating and helping the caregiver meet the needs and ease the process for the patient. There’s usually a lot of frustration that the caregiver feels with their loved one as the disease progresses. And the deficits become more and more overwhelming. So, we tend to review behavioral techniques that can ease the tension in the household. We can help them with treating comorbidities to maximize their time at home. And we do everything we can to help the patient age in place, which is often a great benefit for everyone - avoids unnecessary trips to the emergency department, unnecessary hospitalizations. Host: Thanks for joining us today, Dr. Torres. Dr. Torres: It was my pleasure. Conclusion: Thanks for listening to Medical Intel with MedStar Washington Hospital Center. Find more podcasts from our healthcare team by visiting medstarwashington.org/podcast or subscribing in iTunes or iHeartRadio.

On this episode I discuss the pharmacology of donepezil. Donepezil is an acetylcholinesterase inhibitor. In dementia, that is a deficiency in acetylcholine and donepezil helps preserve this neurotransmitter. Donepezil can cause weight loss, GI upset, and diarrhea. This is an important monitoring parameter in our dementia patients. There is the possibility for donepezil to cause bradycardia and insomnia. Keep an eye out for these adverse effects as they can and do happen in real practice. Anticholinergics are notorious for blunting the effects of donepezil. We must look out for drug interactions from older anticholinergics like diphenhydramine, amitriptyline, and hydroxyzine.

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Editor Helen Frankish discusses highlights from the April issue: including the EPITHET study of alteplase treatment 3-6 hours after a stroke, and donepezil treatment in patients with CADASIL, a genetic form of vascular dementia.

Donepezil has been shown to be well tolerated and to improve cognition and global function in patients with mild to moderately severe Alzheimer's disease (AD). The current trial was undertaken to investigate further the efficacy and safety of donepezil, in a multinational setting, in patients with mild to moderately severe AD. This 30-week, placebo-controlled, parallel-group study consisted of a 24-week, double-blind treatment phase followed by a 6-week, single-blind, placebo washout. Eight hundred and eighteen patients with mild to moderately severe AD were randomly allocated to treatment with single, daily doses of 5 or 10 mg donepezil, or placebo. The two primary efficacy measures were: a cognitive performance test, the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and a global evaluation, the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC plus). Secondary outcome measures included the Sum of the Boxes of the Clinical Dementia Rating Scale (CDR-SB), a modified Interview for Deterioration in Daily living activities in Dementia (IDDD) and a patient-rated quality of life assessment. Statistically significant improvements in cognitive and global function were observed, as evaluated by ADAS-cog and CIBIC plus, respectively, in both the 5 and 10 mg/day donepezil groups, compared with placebo. Treatment-associated changes were also observed in functional skills, as shown by improved scores on the CDR-SB and the complex-tasks component of the IDDD. A dose-response effect was evident, with the 10 mg/day donepezil group demonstrating greater benefits in all outcome measures than the 5 mg/day group. Donepezil was well tolerated by this patient population and did not produce any clinically significant laboratory test abnormalities. The results of this study confirm that donepezil is effective and well tolerated in treating the symptoms of mild to moderately severe AD.