 Thank you very much for inviting me to do grand rounds of truly an honor. Today's topic is going to be on screening for dementia. We'll talk, give an overview of dementia with focus on Alzheimer's and some rules of thumb for differential diagnosis of dementia. Next we'll talk about Alzheimer's versus mild cognitive impairment. We'll ask why should we screen for dementia, and finally talk about what we can screen with. Dementia is a growing problem, particularly as the population ages, and you can see the graph here that the number of cases has projected to double every 20 years or so. It's a common and growing problem. The definition of dementia is a decline in cognitive function, sufficient to interfere with daily activities or occupational function. Dementia is more of a syndrome than a diagnosis. There are many different causes of dementia. That's one of the most frequent questions I get asked by patients is, what's the difference between Alzheimer's and dementia? And well, dementia is the general term. There are many different causes. Alzheimer's is one of the most common. So there are primary dementias, Alzheimer's, Lewy body dementia, and temporal dementia, normal pressure hydrocephalus. There can be dementias associated with other neurological diseases, Parkinson's patients develop dementia as do honeytons and MS patients. We have far enough along can also become demented. There's a number of medical illnesses that can predispose or cause dementia. Toxins and meds are an important cause. There's so called pseudo dementia or severe patients with severe depression. It's important to distinguish. There's vascular dementia, which can be either due to multiple small strokes or few large strokes. And probably in the like 70s and 80s, certainly the 80s, the most common cause of dementia is actually a mixed Alzheimer's vascular dementia. It's important to be aware that, of course, neoplasms can cause a dementia, neoblastomas and so forth. There's a number of infectious ideologies, HIV, Acropocytesfeld, Neurocephalus. In the case of that recently, it's pretty rare these days. And nutrition, chronic alcohol, something to consider there. So the standard dementia workup, you're all familiar with, CBC, ChemPanel, B12, Thyroid. Maybe check for inflammatory markers. EG is kind of optional, usually unless we really think the patient's having seizures. A few screening infectious disease labs, MRI of the brain to exclude certain adversarial causes. Biomarkers, we'll talk about that more in a minute. I think you're going to become critically important. That said, though, the estimate of reversible dementias is very small. But the most important workup is a careful review of medications, alcohol, and substance abuse history. In my experience, I've been amazed sometimes. You know, talking with a guy who seems like a very standing citizen in straight sugar, re-asking how much they drink. And, you know, they're downing several highballs a night and having four years. And if they can stop drinking, that might, you know, I can play a definite role in reversing their memory problems. It's very important to get feedback from an informant, usually the wife or a son or daughter, on their perspective of the patient's functioning. You should inquire about educational occupational history so you can get some idea about the patient's background. And sleep history, some patients with memory complaints can be related to obstructive sleep apnea, which is a reversible cause. Plus, there's increasing evidence that sleep apnea is actually a risk factor for Alzheimer's disease. There's something called the lymphatic system which clears amyloid is active during sleep, and that's impaired in people that aren't getting a good night's sleep. So quickly, here's some rules of thumb that differential diagnosis of common dementia symptoms. So for Alzheimer's, you have a typical story of gradually progressive history of memory loss. There's fairly minimal vascular disease on MRIs. On the other hand, if you have a stepwise history, multiple vascular risk factor, and the MRI shows strokes, then you think of vascular dementia. If patient is, you know, again, up in their 80s or so, and they have strokes on MRI, but they're kind of a gradually progressive history that probably you're looking at a mixed Alzheimer's and vascular dementia. On the other hand, if the patient is relatively younger and has prominent behavioral problems, then they can behavioral vary in front of temporal dementia. If they have a problem with gait disturbance and a trigger of megalomy, you'll think NPH, well, I'm sure I do sephalus. And if they have concurrent Parkinsonism, visual hallucinations, and marked day-to-day fluctuations, that's the homework for diffuse Lewy body dementia. Okay, so a little bit about basics of Alzheimer's pathogenesis. So it all starts here with the amyloid precursor protein. Which has a carboxyterminus in the cytoplasm and the amyloid terminus in the movement. And the key action here is taking place in the transmembrane portion, primarily right near the transmembrane portion. APP is a very evolutionarily conserved protein, and scientists have been working for some time on trying to define exactly what it does. It's involved in embryogenesis and synaptogenesis, functions in the peripheral nervous system. So that was quite a bit. Now it's processed by a variety of enzymes. And so here's the amino acid sequence of the protein used to transmembrane it right outside of it. And there's different cleavage sites for different enzymes. And this is very important because there's a non-amyloidogenic pathway for cleavaginit, amyloidogenic pathway. So for the non-amyloidogenic pathway, first the APP gets cleaved by alpha secretase and then gamma secretase. And the fragments it produces are harmless. On the other hand, if the protein is first cleaved by beta secretase and then gamma secretase, that's when you get release of this abeta-42 or abeta-40 fragment that is gone together and form the pathologic hallmark of Alzheimer's, which is the plaque. The other pathologic hallmark tends to develop later in Alzheimer's, the neurofibrillary tangle, which is intracellular, whereas the plaque is extracellular. And the NFT is related to tau pathology. So Alzheimer's progression, in the first stage, you just have the abeta-plac pathology. But you have biomarkers like the positive anulary PET scan or low cerebral spinal fluid abeta-42 levels. The reason why it's low is because it gets sequestered in the extracellular flax and doesn't circulate in a spinal fluid. That's a little bit counterintuitive. Tau, on the other hand, in the second stage, CSF tau becomes elevated. And here's where you start to get things like brain atrophy on an MRI scan. And you can also see abnormalities of metabolism on FTG PET. In the third stage, you have biomarkers plus subtle cognitive decline. So you start to see problems. Very first clinical symptoms are only in the later stages, actually, as it were, that then lead to more over mild cognitive impairment in Alzheimer's disease. So there's the amyloid hypothesis of Alzheimer's, which has helped sway for decades now. And some of the evidence for that includes that genetic mutations in the APP protein, or also Precinal 1 and 2, which are involved in amyloid processing, cause a familiar Alzheimer's disease. Trisomy 21, Down syndrome, APP is on Trisomy 21, is on the chromosome of 21. So you have an extra dose of it, and there's also evidence that the abeta pathology can occur decades before you get any clinical manifestations. There may also be interactions between amyloid formation and subsequent tau formation. So the graph here shows that the, again, the first thing that happens is amyloid accumulation. That's followed by synaptic dysfunction in the tau media, the coronal injury. Then you start getting brain structural damage that's visible on high skins and form of atrophy. And then finally, you start getting cognitive aspect, a little bit of cognitive decline, and then it becomes more visibly visible. So biomarkers. So there's the floor beta peer or amyloid scan, is a light end that binds specifically to amyloid clack. So here we have people at different stages of amyloid pathology. If you have mild cognitive impairment and a positive amyloid scan, your chances of progressing in Alzheimer's disease are seven fold higher than if you have a negative amyloid scan. One problem with it is that you're going to have false positives and cognitively normal elderly. But on the other hand, it could be that these people are actually on their way to Alzheimer's. Or perhaps there's something about their biology that's resistant to amyloid. Great question. No. Two big problems with amyloid scans, they're usually not covered by insurance and they're very expensive. There are other Alzheimer's biomarkers, hippocampal atrophy. There's a program called NeuroQuant that can define hippocampal volume. So if you have a low volume on a NeuroQuant analysis that is consistent with Alzheimer's. CSF amyloid tau, we mentioned earlier, the ApoE4 gene. So ApoE4 is the major kind of risk factor, a genetic risk factor in the population for Alzheimer's. But you can't, you know, you can have before and not have Alzheimer's. And conversely, you can have only E3 and still have Alzheimer's. But if you have an E4 allele and you have some memory symptoms, the odds are that does increase the chances significantly that cause of your memory problems really helps Alzheimer's. Other AD biomarkers, we mentioned temporal parietal hypermetabolism on FTG PET scans. Blood tests, we're really looking forward to those and there are some under development, particularly phosphorylated tau proteins or the beta 42 ratios. They're not quite ready yet for climb time. They're not reimbursable, but my feeling as the next year or two, we're going to have, that will be very helpful. So you've probably all heard in the news about adicandamab, drug made by Biogen. Will it be a game changer? So adicandamab is a monoclonal antibody that binds and clears and we plaque. It was zero doubt that it does that. And it's very clear that it's effective in getting rid of amyloid plaque. The controversy is over the clinical effect. There's a long saga of what happened. So the initial trials were halted by Biogen after futility analysis. But then after they reanalyzed that, they found that patients with mild cognitive impairment, mild ulcers did show some benefit and more evidence is accumulated, for example, for the extension data after two years, the patients who had a decrease in p tau 181, this is a blood biomarker, had better outcomes on clinical measures, more trials are planned. Really has their own drug, dynamamab, which looks somewhat similarly in their trials are in progress and have shown some positive results. Danziger is really expensive. It started out at 56 K a year and Biogen cut it to 28. And the risk of something called area, amyloid-related imaging abnormalities, these are like inflammatory changes that occur and are visible on MRI. Many times it's asymptomatic, but it can cause confusion and headaches. You have to opt to drug if that occurs. Although they do have it as the later on when it calms down, you can restart it. But the risk of area means that you have to do routine MRI monitoring as well as MRI scans, if you suspect that there's clinical effects of an area going on. Now, CMS recently ruled that in order to be reimbursed, in order for an academy to be reimbursed, you have to be involved in a clinical trial that meets their criteria. And right now, that's not going on. I think the trials are in the process of getting formulated. But on a practical level at the moment, given that most Alzheimer's patients have Medicare insurance, without participation in a clinical trial, you're not going to get reimbursed. Okay, next topic is Alzheimer's versus mild cognitive impairment. So again, the natural history of Alzheimer's start out normal, then you start to decline a bit, get the MCI stage, mild Alzheimer's and severe Alzheimer's. So mild cognitive impairment, or if you have a positive biomarkery, you can call it prodromal Alzheimer's disease. So kind of a fuzzy boundary between normal aging and dementia. On the one hand, the cutoff to a normal person means that your memory or other cognitive domains are not what is technically defined as one and a half standard deviations below the mean on some cognitive test. And then to distinguish from dementia, there's no significant occupational or functional impairment. This is a bit of a fuzzy boundary. One person's MCI can be another person's dementia. Take two people who have identical cognitive functions. Okay, and one of them is a high powered corporate attorney. Well, it may not take all that much blossom memory for him not to be able to function in his job. So he has to take disability retirement. So he's in the Alzheimer's range. On the other hand, the other guy with the same degree of cognitive impairment. Okay, so he doesn't remember the football scores. We can be forced. No big deal. He's MCI. The older Alzheimer's drugs like colonist recent numbers have not been shown to work in MCI. But stay tuned out where to say about that. So distinguishing normal from mild cognitive impairment is sometimes an art. There's kind of two clinical situations. One is both the worried well. These are older people that notice some senior moments and they're worried. Oh, God, am I getting out of this disease? But they don't really have it. And the second situation are patients that don't have any complaints themselves, but you do a screening cognitive test and they have trouble with it. So using, you know, various cognitive tests, the mini mental and I have my own test, which I'll introduce you to later, can help with the assessment. I mean, anybody who's got a mini mental 19. Now, they're going to be in the dementia range, not MCI. How are particularly people with intermediate sources scores? You have to factor in the effect of drugs, medical illnesses, stressors, educational occupational background. So sometimes it's hard to tell and you may just have to follow the patient all the time. Some helpful tools in determining crossover from MCI to dementia. They're caregiver assessment tools, which I'll show you in a sec and asking the caregiver this question, would you feel safe leaving the patient home alone for a week? They say no, that's intuitively that they feel that they don't think the patient is cognitively well enough to be able to manage on their own. And the degree of deficits on the mental status is how bad are they in? Mini mental or broken, but it's a continuum rather than a bright line. So I'll tell you about the functional activities question here. This is again, caregiver filling it out. So zero to three scale and 10 items covering handling finances, shopping alone, reading skill, keeping track of events, remembering appointments, traveling out of the neighborhood, and so forth. So this is what it looks like. And by the way, if any of you are interested in getting your copies of these questionnaires or screening testimonials, describing later, feel free to email me and I can send them to you. So again, the caregiver fills out the zero to three scale these various activities. You have a score of ranging from zero and no problem three completely unable to perform. Another helpful item for your history is the 88 outside of his disease, eight informant questionnaire. Here, the caregiver fills out, yes or no, if there's been a change in the eight items, such as repeating questions, storage statements for the correct month or year and so forth. So there's some overlap of the FAQ, but there's also some like earlier things that it has that are sensitive. Here's what it looks like. The caregiver just checks yes or no for these eight different items. And you have a score of greater than two as a sensitivity of 74% and specificity of 85% or a dementia diagnosis. So this can help kind of round out your history here, these different problems that the patient may have. Another questionnaire that I like to use is the neuropsychiatric inventory short form. This is a two page form that gets at no behavioral symptoms. These tend to become more prominent mainly in the moderate dementia stages. But the caregiver rates for each of these things like illusions, hallucinations, hesitation and so forth, depression, anxiety. Whether it's mild, moderate, or severe, and how much distress it causes the caregiver. Anywhere from zero does it bother them at all. The five is very distressing. Carrier or stress, that's actually a major problem in out-term patients that patients may be sort of blissfully unaware that they have problems, but caregiver certainly isn't. And here's the second page of the MPIA. Short form. So what happens to MCI patients? So the conversion rate, Alzheimer's disease varies among studies. Usually, most of them, I get it around 10 to 20% per year. Again, if you have a positive biomarker that indicates you're more likely to go. But on the other hand, some MCI patients can remain stable for many years. A small percentage could even revert back to normal and then progress again later. The factors that predict or prevent conversion are underactive investigation, clinical things. We'll talk about it in a minute, like exercise and so on, as well as biomarkers. American Academy of Neurology recommends MCI patients to be monitored at intervals for evidence and cognitive decline. Okay, why should we screen for dementia? It's the next topic. So Alzheimer's disease is often misdiagnosed. They're often diagnosed with some other cause of dementia or depression, maybe, or it's just normal aging, stroke, etc. So only 28% of patients that had Alzheimer's were initially diagnosed. And dementia is, in patients over 65 and primary care practices, is estimated to be around 10% or so. But of these, it's estimated that around half are not actually diagnosed. So who do they fool? Well, they fool themselves often. There's a phenomenon called anosognosia where patients are not aware that they have a problem. So if you ask an older person, hey, have you noticed any memory problems as you're getting older? And they say no, haven't. Well, that may be true. And they, in fact, are normal, or it can actually be a manifestation of the disease. They do have memory problems, but they don't have the insight to recognize that that's the case. So they can fool themselves, they can fool the family as well, give some reasons why that's the case in a minute, and they can fool you. So how do they get away with it? Well, social skills are often preserved early on in Alzheimer's. So patient with really mild symptoms talking to them in your clinical encounter, you really may not pick up that, you know, this person has a problem. And also Alzheimer's, you know, insidious onset. So excuses can be made for gradual loss of function, such as it's just age. I mentioned earlier that, you know, retirees may not be stressed intellectually. So nobody notices their subtle cognitive decline. And from the family's perspective, they may dismiss it and say grandma is fine, you know, she still recognizes the family after all. But again, of course, it's short term memory that's affected early on in dementia. Or denial, his memory can't be all that bad. He can remember all about his high school graduation. And on our part, you may not ask routinely about their complaints, may not test for it to the gloss over it or blame it on pressure. Okay, so why should we screen for dementia diagnosis in an earlier stage allows for better planning, such as financial planning, giving power of attorney and so forth. Driving risk, we'll talk about in a sec, can be a postoperative delirium risk factor and medication compliance over this in a minute. And as diagnosis of early dementia is often missed, unless we use screen tools. If you do a screening test and it's negative, that can be a positive thing because it establishes a baseline. In my practice, it's been very helpful if I've seen the patient a few years before for some other reason. And I did a screening test and they did okay. They come back in two or three years saying, you know, my memory is starting to go. I think then, you know, repeating the test, you can compare it directly. And if it's negative, you can provide the patient reassurance that, you know, right now, everything seems to be okay. Keep an eye on it. Sometimes doctors will just prescribe the nepozyl, the patient has a complaint. And that their memory is going and not, you know, establish a form of diagnosis. But there is a problem. Earlier treatment, even with the older drugs, maybe more beneficial than later treatment. This is somewhat of a controversial statement, but there's some Scandinavian studies recently that indicate that patients that are started on colonoscopy inhibitors early on tend to have less like nursing home placement and mortality than patients that are started later. And another reason is it's now part of that here requirements for patients that you do some kind of screening. So postoperative delirium. So I asked her over at Hopkins did a review of hip fracture patients included that preoperative cognitive impairment is the thing that's most consistently associated with postoperative delirium. And the American Geriatric Society has clinical guidelines for delirium prevention and treatment. But I don't think anybody's really done a study yet of implementing routine dementia screening for surgeons who are planning on doing hip fracture repair and then taking action to prevent delirium and do the patients actually have a lower script delirium. So that'd be a really good study to do, but certainly if the patient has screens, you know, that they have significant cognitive impairment. That should alert you that they do get some kind of elective surgery and see if they could have problems. Drives the risk of crashes increases without service. Patients definitely if they're in moderate to security measures should not drive at all. mild patients. I usually recommend they get a driving safety evaluation, the OT or the motor vehicle association. There are certain programs like Sinai and Good Samaritan that have occupational therapy driving emails. If they flunk, then their license gets pulled. And that can be a major, you know, kind of problem with these patients that they're not happy about the positive independence from driving. There's better than getting into or, you know, crash. There's old ladies trying to order cheeseburger and large fries from the mailbox here. Spectators are commenting that testing seniors for driving isn't a bad idea. Medication compliance. So here's a quote in clinical practice awareness of non adherence as a result of cognitive impairment is relatively low. Most important step is really detection of cognitive impairment. So you have a patient with cognitive impairment, you don't realize it. You may be upping their medications. Not because they're not working, but because the patients are not taking them consistently. So patients that have some client, they may need additional oversight from family. Early versus later intervention. So I mentioned Alzheimer's drugs that we have. Presently they're widely available. Can offer symptomatic benefit at least. And then there's a variety of lifestyle things like exercise and cognition. The more you exercise, the less likely it is that you become the meta. There's a lot of evidence for that. Staying cognitively active, socially active dietary factors. A heart healthy diet diets that are rich in flavonoids may have protective function. So there have been some clinical trials where take patients with MCI. And you have them, you know, under start an exercise routine. You know, intervene dietarily, etc. And some of them have had a positive result. Although others have not so that's still kind of getting fleshed out. Okay, finally, we come to what to screen with so. There's a variety of dementia screening tests. Sure, we know. We'll talk about the mental mocha. Something called memory impairment screen clock draw many cod. Hopkins verbal learning test slums test and finally my own test. Q and E are quick and easy. So here's a good old MMSC. You guys are all familiar with it. I'm sure. I point out and I mentioned this again later that the things that are most sensitive on this test. For dementia, the three item recall and date. That shows up early on. On the other hand, things like naming a pen or watch. You don't lose that through your pretty far gone. Those items are sensitive to both mild water or severe dementia. So it's useful for following patients throughout the course and there is evidence that. You know, the worse off your MMSC is more likely it is that you lose. These activities of daily living abilities. With the more severe many mouths being associated with. More easier ADLs like being able to clear the table versus traveling along. Problems with the minima. Well, it's not really sensitive for why other intelligent patients. On the other one hand, the other is not specific for patients with low education or IQ. There's some scoring issues with it like some many metals. You have the serial sevens versus the world backwards, which would be used. I practice in Baltimore city. So. There's no such thing as asking what county or it's a trick question. It takes a little while through ministry is now copyrighted. So if you're going to. Publish anything with it, you're supposed to get permission from the. People that on the copyright, although I've yet to be busted by the many mental state police. On the other hand, it's still useful for staging and communication. Everybody understands, you know. Roughly with a mini mental state score of 17 means versus 26. Now the mocha is more difficult for the many men. You should keep in mind it was a norm that smart Canadians when your college education. And cut scores are much lower in other populations. And in particular in the demographic of Baltimore city where you have. Patients that have a lot of demographic challenges with education and so forth. Um. That's using the cut score of 27 or 26 just. Is too non specific. I find it particularly useful though for is for people, you know, really smart over people that have mild deficits. It does take 10 to 15 minutes to administer. And so here's the test. It has a five item recall separated by a number of other things, including the serial sevens, which is education sensitive. The memory impairments free. So this is a four item. semantically encoded items that patients asked to remember to show what that means in a sec. So they read a lot for words from different categories and they're given a cue and asked to match the word. And then you ask them, okay, what were the words I showed you on each paper two minutes ago. And scoring is two points for each. One they recall spontaneously one point with a cue zero if they don't get it even with the cues which is zero to eight scale less than four is dementia five to six is borderline. Seven days is normal. So I use for example. United Nations platter chests and emails and patient reads them and then you say okay, which one of those is a dish platter. Email organization went game chess. So the semantic encoding helps with our specificity. So the MIS and the Einstein aging study compared to a straightforward three item we call did have higher sensitivity and specificity for detecting dementia. Talk to our test. So ask the patient draw a clock. So that's a 10 past 11. I'm a various scoring systems been proposed. In practice, I really don't think people follow these different scoring system, particularly. It's mainly gestalt if it's normal or it's not very sensitive to really mild patients. It is part of the mini college. We'll talk about it in a second is worth three points on the mocha. So the mini college is a three item recall with a clock draw in between. So I was just going to call the six items screener, which is the day of the week date and I'm sorry day of the week month and year with a three item. You know, that's in between learning and remembering the three items. The minicog is basically pass fail. But it is judged to be one of the best fast screens. Although it does rely on this three on recall. And because it's mainly past failure can't really use it to follow progress and patient. Next step is the Hopkins verbal learning test, which I really like. This is a test. It was developed by Jason Brant over at Hopkins years ago. And it's a list of 12 words. And there's four for them in three different categories. This instance, it's animals, jewels. And shelters. And so you read the list. And the patient repeats back as many as they can to go through three times. And so the initial recall scores the summer family to remember on each of the trials. And then there's a discrimination index. Which is a patient just says, yes, you know, if the items are on the list. On that list, go through 24 words here. 12, which of course are on the list. And 12, which are not six of them being the same category like Ruby is a jewel. Cat is an animal. And you take the number of correct versus and subtract the number incorrect to get the discrimination index and you add that to the recall score. You get a total score. Total memory score and under 24 is just a live outs ever since I bore a line. And this is under 28 is 28 and under a very handy, very sensitive is to do a 10 minute recall. So you come back and surprise the patient. Like after doing their rest of their exam or something 10 minutes later say, okay, what are the words on that screening on that long word list that we did a little while ago. And they should be able normal as seven or up. And six or below indicates there's a problem. This tenant recall is pretty sensitive to memory problems. The slums that St. Louis University, the state was developed for veterans but subsequently validated other populations. Test orientation. We call with both a five item list here. And also there's a story that's told. I'll ask several questions about the story. It's been shown to be better than the mini mental at detecting MCI like the mini metals of 30 points scale 27 that was considered wrong. The last few minutes I'll tell you about my Q&E test. It's working easy takes 95 seconds and so one of the major impediments to busy primary care docs doing dementia screening test is time. This is one of the fastest, you know, tasks you can do. I there's actually two parts to it. We're only going to be talking about the Q&E part. Rational. So what's the single most sensitive test for outsiders? It's the late recall after initial coding. A good test for outsiders or semantic fluency animals and many can use that actually as a standalone test. But it is a little bit educationally sensitive despite so orientation to date. I mentioned the MMSC. And so for the most bang for your buck simply insert of a good test in between encoding and recall. So there are four components and coding type of orientation, verbal or semantic fluency and I could recall. The encoding part I use paired associates like red ball, white horse, blue key and patient has to repeat them. Now, if they mess up the encoding scores based on how many times you have to repeat the audience before they say them correctly twice, not necessarily consequently. So if I have to repeat once, I don't take off any points for that. I'll point out the higher scores are worse on the Q&E. So it's kind of like negative points is how you can think of it. So zero is if I have to repeat it once, they don't take off that they may not have paid attention. They didn't hear, etc. But if I have to repeat again, that's one point. If they still don't get it, I have to repeat it again. That's two. And they still get it after that. I'll just go one by one and score three points. So you can get a sense sometimes just from this. Anybody who scores it two or three. On the encoding aspect is going to have problems down the line. Okay, then you ask the patient, okay, what's today's date? Allow, I allow one day plus or minus on the date. Two if you have the wrong month three off if you have one year. So I consider more of a cognitive sin not to know the month date and even more so not to know the year. So I read it accordingly. Unlike the meaning not all or mocha where it's just one point off for each of them. So you can lose up to six points on that. Okay, then it's animals in a minute. And I also take off the repetition now when I have a patient this I'll like note down, you know, how many, you know, what time it is that we started exactly the second hand. So, and write him down as patient goes along. So zero points is 14 or more one point 10 to 13 animals to seven to nine, etc. Let's take off a point. If they have more than one uncorrected repetition. And Tuesday have more than three of uncorrected repetition. So this is when the patient offers up an animal as being a new, you know, animal. Rather than saying, you know, dog, cat, horse, cow, pig, I sent dog, I sent cat. So I don't think off of that. But if they offer up a old animal, not recognized, they said before. That's a repetition. And else other patients tend to do them. So then finally a cute recall one of the three things I gave you remember. You don't get further cues like saying they have colors. So it's a zero to six zero if they get them all right six if they are never any. Once in a while they may mix them up in which case it's a happy free child that was on the list but incorrectly paired. And so some of the items in each section is total Q&E score. So normal is zero to two threes kind of borderline. So three of the Q&E scoring zero to three for encoding up to six points for temporal orientation. A number of points you can lose on category fluency and recall. So zero to two is normal threes kind of borderline over three is cognitive impairment. I did a study some years back with a guy, Dr. Alan Trubin, a neurologist who runs a mammary clinic in Spokane. And he had his nurse test patients with a Q&E and something called the Washington adaptation of the Attenberg's Climbing and Evaluation. So the ACE test was in England and it's a hundred point test and he adapted it for Washington state. For example, by asking who's the governor of Washington state rather than who's the prime minister of England. And you can extract out of that the meaning of the state, the mini cog, the six item screener, which I mentioned briefly earlier in a clock. Dr. Trubin did not know the Q&E results. He just had the ACE test available. And he made the diagnosis of normal MCI or Alzheimer's disease or other dementia or clinical programs. So how did it work out? So we stratified patients by their mini mental state scores. And there's very mild patients we call those are people with normal mini mental states of 27 to 30. The Q&E of score four and above picked up like 70% and was statistically better than the other tests. And the Q&E was, you know, like over 90% picking up. Here's one or two patients who had mild that service with mini mentals of 21 to 26. And overall, you know, it was like 80 plus percent picking up mini mentals patients who were diagnosed with dementia with mini mentals of 21 to 30. And I don't know if the clock draw here, not do all that great compared to the other tests. So summary slide here of different mental status tests, time less than two minutes is educationally sensitive. Is there an adequate point spread to follow the patients over time? And does it require the patients to draw it right? That could be handicapped if you're patient has some motor impairment or you're testing in a hospital setting. So the mini mental, for example, takes longer than two minutes. It is educationally sensitive. But it can, you can use to follow the patient over time. My test is less than two minutes. The animals may have a little bit of educational sense that they, but it shouldn't be for the other things. And it does have an adequate point spread to follow patients over time. But once patients hit bottom or severe, you can't use it. It's really just following patients over the like mild course. So in summary, cognitive impairment, dementia is often detected in the doctor's office. Patient and family may be unaware as well. You can improve your detection by using some of these screening tests. And detection is important social consequences for the family as well as the patient. And interventions for treating cognitive impairment are available. Hopefully drugs like Atacanamide or its successors proven to be effective in the earliest stages becomes even more imperative that you identify these patients early in the hour. Okay. Thanks very much for your attention. I'll point out my email address here again if you're interested in trying some of these tests after yourself and what forms are just so many. Thank you.