STGEC G&G GR: Lewy Body Dementia (2015)

you and the faculty members in the geriatrics division in department of medicine and I am a full-time be a physician who works in mostly in home care but also in the memory disorders clinic which dr. Boyle and portis and I developed some years ago just because we were seeing such a need for that so a lot of my interest in this comes from from working in that clinic for over 10 years so my talk is about whether it makes sense to try to make a specific diagnosis of Lewy body dementia versus other dementia types and I'll try to convince you that it does because I think I think it's it is useful I kind of learn best by from actual patients and real experiences so I'm going to start with a real case sometimes I make these up I'm not I'll be honest this actually is real and nothing in here has been made up so this is a good one he was 82 years old mr. Steve I'm Janice diabetes hypertension heart failure paroxysmal supraventricular tachycardia chronic kidney disease and he supposedly has had a TI a little mini stroke sometime in the past his history is also positive for intermittent severe hypertension but at the same time very severe drops and his blood pressure when he stands off this has been going on for three years and it's been so bad they worked it up for some rare diseases like pheochromocytoma so adrenal tumors and things like that because of these dramatic blood pressure swings we just started with it we're just starting our case the first battles are hearing so he's good so there's not you haven't missed anything significant I talking about this this man that was admitted to my home care program in october two thousand six he he was patent was on a load of pain aspirin clopidogrel calcium vitamin d food report his own to the scripture verse of my potassium in to me for help Leslie for folks sundowning or nighttime confusion so when I thought I found from his chart when I talked with him these are things that he told me he had a friend who was with him and then she told me that he thrived as and yelled so loudly in his sleep than all the other the other neighbors in the trailer park complain about the screaming and crashing at night that they can hear next door in the next door he described himself nightmares these vivid violent images that seem grill for a few minutes after he woke up and he would actually throw his body out of bed and break the furniture and then wake up frightened and barricade himself in his room before he kind of realized oh yeah that was a dream he also got up to urinate four times a night he had a history of frequent Falls and and he he said you know my memory is just not very good there's something wrong there so those are the things he told me about on exam when he was lying down as blood pressure was 135 over 90 we stood up it went to 98 over 70 its heart rate didn't change so he had a regular heart rate of occasional extra beats had a soft systolic heart murmur and maybe is the third target sound a little ankle edema he also had a wide base gate and kind of a souped posture and short steps when he walked his labs remarkable for a creatinine of 2 which is pretty bad kidney function actually normal b12 folate to us test for syphilis all those were normal and he didn't have a little right subcortical stroke on his old old subcortical stroke on his casting so that's that's the patient when I did some testing his many men was 22 out of 30 he had high school education and actually had seen the corner of psych testing they had mild impairments of attention in recent memory moderate impairment of visuospatial function and some impaired processing speed and they told the psychologist who physically attacked on streams and fight with ghosts and demons in the night Nia past this revelation something that didn't come up when I talked with him other than these nightmares so what information would he want to want to determine okay so he has a cognitive impairments is he demented this is more aimed toward of residence or fellows so but we're just talking today milk I'm not going to ask what I was going to ask that and what I was trying to get at was you want to know is he functional impaired by any chance do they actually make a difference in his ability to do his normal activities or not and in his case he was having some difficulty with finances and with managing his medications so yes the deficits more significant enough perhaps the call saying that if you mention so with the wisdom of 2006 i diagnosed him as having a vascular dementia because you know we had risk factors and he had a little stroke on his scan I tried to manage those risk factors I tried to taper the olanzapine you know just keep the integral for stroke prevention and trying to produce all risk in any way that I could for him and we'll come back to the case later so that's that's just that's our patient but I when I looked at different dementia types and estimates the this is just aggregated from my review of the literature cross-sectional studies about sixty percent Alzheimer's twenty percent Lewy body fourteen percent vascular and six percent other it's just kind of the ranges that I came up with given the literature I wanted to show you what a little attention looks like that round compete thing there so they're least these round inclusions that contain abnormal neurofilaments and also contain towel and ubiquitin boots what's interesting is they're not just in the brain they're in nervous system tissue in multiple other areas so the PAL a shows Lewy bodies in the sinoatrial node in the heart these shows and we saw the gastric junction see in the adrenal medulla and the d of the celiac ganglia so you can see how this could have widespread effects beyond just memory problems if they're throughout your autonomic nervous system the main component is this compound called alpha synuclein which is a protein it's normally an unfolded single protein but it can fold and it can aggregate together in all sorts of forms and be in various places in the nerve and for these three bodies what's one interesting thing is that there are other diseases other than movie body disease to have pathologies in this this substance Parkinson's is characterized by the Lewy bodies but then also multiple cysts the essential tremor and Josh a disease and otherwise of some of the storage diseases also have pathology in this substance so again this is more for this is sort of what we were talking about in clinic this morning so how do you save somebody who has cognitive impairment is demented and that's what this is going over a state will decline from a previous level of function so that would exclude people who have developmental disabilities who have always had those those that's not considered a dementia in the usual sense celestia decline it has to be bad enough to interfere with independent functioning in that person's life and not be caused by a delirium or primaries you know reversible psychiatric illness so we didn't talk today about what the criteria for movie body dementia were so we didn't actually didn't ask you those so I'm not going to put you on the spot now your fear unfortunate to be the only rest of its air today dude did I okay um hallucination is usually a maximum lining of course we fine one minute and then all the next it's an F symptoms of Parkinson's they could have some piece of Marcus's you've done very well you've got the three core nature's right like that what other things have you um well I know one thing that we leave them we asked in the matter did they have REM sleep behavior disorder and that can increase there is you've said this up perfectly so thank you so there are four features and suggestive features first you have to qualify that to actually have dementia as we talked about with core features as you said our parkinsonism visual hallucinations and these fluctuations and status much more dramatic than people of Alzheimer's have so often people will think that the person has had a seizure or a stroke because they're just so different from one day to another and you know I've seen that where we track the cognitive scores as we see people in memory clinic and these patients awful have these just huge fluctuations you know from one visit to the next there are also some suggestive features severe sensitivity to neuroleptics REM sleep behavior disorder and then reduced on basal ganglia dopamine how take on functional imaging which is not something we do very much here but it is part of the ultimate targeting with the formal criteria so with these criteria if you have greater than two more teachers required for a diagnosis it's eighty-five percent since seventy-three percent specifically if you put REM sleep behavior disorder into the four features it actually improves the sensitivity and you keep the same specificity so now in 2005 they actually changed the criteria so that you could have once one core and one suggested instead of needing two more features to make a diagnosis I'd have a REM sleep behavior disorder video but it's on my my laptop I can show you it just kind of pass it around and and just hit go and watch it it was embedded in the presentation but you know in the trash and well in the transfer we didn't have time to transfer that so I'm cute yeah that that would probably be as I can do it you can just pass it around and hit play it's very short and while I talk about stuff okay so so doesn't it have talent but the sounds out there you just watch the REM sleep behavior disorder ya know what's weird when I went looking for this stuff it was kind of hard to find and you would be shocked to find out how many people videotape their dogs and cats while they sleep oh there were so many dog and cat bombings more than welcome to yeah so originally behavior disorder wasn't described until quite late 1980s or 90s ah so so it's a relatively recent thing so what's the difference between we body dimension Parkinson's dementia since Lewy body has parkinsonism they're both have Lewy bodies that was one question people respected a that Easton movement he's going to receive it the cognitive disorder they most likely as you know because my pieces and then shed until several games all right so you're you're right on track with that so it's kind of an arbitrary distinction so to be called Parkinson's disease dementia the motor impairment receipts the dementia by a year or more whereas dementia with Lewy bodies the motor and cognitive impairment one year each other majority of patients who present with more classic Parkinson's disease do the majority to develop a dementia within 10 years so so I wanted to talk for a minute about these diagnostic tools that we rarely use darker royal talks a lot about mi DG SPECT but we don't have access to it these tests are reimbursed in Europe and in Japan so they are used a lot in the and that's where most of the literature comes from and then there's a dopamine dopamine imaging is the second one so I EG is iodine one two three metro I odo wenzel wanna be which is why they just invade that so it's an analog of point Anthony so it's taken up by the postganglionic gangly I pre-symptomatic adrenergic herbs when the nerd depolarizes it gets released but it doesn't get metabolizes you can actually can see sort of what the noradrenergic innovation is in life it was a Devon develop as a technique to look at cardiac sympathetic innervation in people with really bad heart disease so but because remember Lewy body patients have autonomic system involvement early in the in the course of the disease it might what was thought that it might get in and use that technique that would work for that as well so there's two meta-analyses that been published about this in the last few years dr. Boyle and this colleagues here published one of the major ones and then there was a we published a major meta-analysis of the all the MIT two studies so I just wanted to point out what what this is talking about what it does the images take taken up again sympathetic nerves and then look at the myocardial our part to mediastinum ratio and it should be in the heart and not in the mediastinum so the heart is here and just the you know the center of the mediastinum up here and then calculate and these are normal this one normal looks like these are too abnormal stands the one on the left is someone who subsequently went under had a heart transplant for severe familiar this is a person who has a center are never going to die and it's either both of those there's not much difference between the the intensity of the in the update here versus here universes here so those are abnormal scans so this is this is from dr. Royals study and what they were looking at doors to see whether this in a meta-analysis whether this technique could differentiate the different types of dementia from each other and from normals and so they're looking at what what ratio would be the best that so it's actually clustered into three groups pretty neatly the normals Alzheimer's progressive supranuclear palsy and all clustered in the normal range actually up around to the Parkinson Lewy body and roost the behavior disorder all clustered really low less than 1.5 and then the frontotemporal and vascular what kind of nowhere in the middle so the ratio that they found that was the best was around 1.8 the other the Italian study has used had a larger sample that is calculated sensitivity since physics of Admiral mi BG and diagnosing compared it with with diagnosis of audiences in specificity this is the dopamine energy say I'm not going to say this one I practiced it but I'm not i can but it's called dastan in its trademarked and it has a high affinity for a presa maximum dopamine transporter in the brain and so that's how you finished those in has taken care women sensitivity and specificity this is what these look like and so they what you compare is imaging brightness and acute pain and versus kind of everywhere else and so this this is normal these are all the others are all abnormal patterns where you don't have that sharp distinction anyway those are those are the imaging studies that we occasionally but don't don't often use one of the things that has said and I wanted to see if it was true is that survival is lower you know in lewy body than some of the other dimensions and so there there are some studies doc this is a woman they will be Williams at Washington University where they have these longitudinal aging studies and comparing survival between those two diagnosis the top graph are this age and mortality and then the monograph breaks it down by gender and so yeah they're there the Alzheimer's are on the dark and to the right and a movie body you can see that there are differences so the people who live the longest or women with Alzheimer's and the people who died the fastest are been with lewy body disease and the other two categories are in between and that's adjusted for kind of cognition or point in the disease course there was this is an interesting study because when you think about survival is not really the only important endpoint this was a prospective study where they took consecutive people with to mention either Alzheimer's of the Lewy body from a group of clinics and did a comprehensive fall risk assessment and followed them for a year and did other other kinds of assessments to and then they found that their end points were time to death or hospitalization of pneumonia or fall I think those are clinically really important outcomes that's probably mine independent and I think again what we can see is that Alzheimer's patients have a much longer time until they have one of these bad things happen then the ee body patients did and then finally this is specifically focused on cause and again kind of time to first fall and so patrols Alzheimer's vascular really buying at harkins using at the wood each group is different from the others but the Lewy body and Parkinson's are are the followers very very largely so I mean understanding that about your patient and how higher as they are for falling I think is important so why make people believe I you to dementia be more likely to fall because it that's one big reason because cart you know from cardiovascular standpoint they may faint or they may get really weak from orthostatic hypotension and fall hallucinations good yes so they going to be reacted in their hallucinations ah yeah that he definitely could that could happen so the parkinsonism and rigidity is a so if they have that as a component that's prominent with their really muddy disease that one could that could clearly make them fall the other is I guess the only other thing is that they tend to have greater visuospatial deficits because of occipital lobe involvement and so again they especially things in the lower part of their visual field may have more difficulty with so all those things make sense why they would fall covered everything that's good the next complication I wanted to talk about Miss delirium I mean we know that people in people with any kind of dementia are at increased risk for delirium and we know that people who get delirious are at subsequent risk to be diagnosed with dementia well we what I didn't know before this but you kind of suspect because delirium kind of sounds like Lewy body dementia in a way when you think about they have perceptual disturbances they have fluctuations may you know maybe there's a common mechanism there so but whether different types of dementia patients have different risks and so there's this space control study from England I like the cerebral function unit at newcastle upon tyne where they took match Alzheimer's and lewy body patients and in a case control study to see whether they had experienced delirium because they have all their records both while hospitalized about a quarter of the Lewy body had whereas only seven percent of the Alzheimer's patients had so that was a significant difference in the Lewy body patients were also more likely to have multiple episodes of delirium so it does look like it it probably is a risk factor but even greater than dementia itself for delirium you somebody mentioned the types of lucenay shins and there's actually they're actually studies where they cattle on these things and it is one of the diagnostic features though the most common content or earth but I listed anonymous people animals body parts you know hands faces things like that none this is like gross body parts but just floating things children friends and family and mechanical things they're often miniature they can be anything from really terrifying like I had had one patient where you know it was the flying spiders think spitting poison you know too I had one person who I said you know do you ever see anything that's not fair and it's like well yeah there's this plant outside my window and it get throws what I watch it then it starts to dance and I said we'll just have follow you said oh no no it's like watching a movie men like Sunday yeah you know so but often there likes a little children or dancers or animals there's you know neuroleptics sensitivity is one of the suggestive features of Lewy body disease and you know I talked to students and residents and fellows it's like oh if you're going to prescribe an electic get there going to be very sensitive to it they may have a bad reaction and I this is the first time in preparing this I went back to see you know what does that based on his a really any data about that and so there there was there was an autopsy series in the where they had 21 Alzheimer's patients and 21 movie body confirmed autopsy cases and then they again had complete medical records and on these patients and they found were that the Lewy body patients were much more likely to have hallucinations and delusions than the Alzheimer's patients so you can see that they're more likely to get put on an elliptic because of the symptoms they have and then of those who got neuroleptics 81 @ % of the Lewy body patients had a pet of adverse reaction vs. only twenty-nine percent of the Alzheimer's patients so when they were talking about adverse reactions they were it was anything from a severe neurologic malignant syndrome to just getting a little stiff so I mean it wasn't quite as terrible as it sounded and these were all with thioridazine and haloperidol the old drugs that we rarely use anymore although so yes they are more sensitive to neuroleptics but with the newer drugs of the degree of problems with probably less than what we would live in this study the REM sleep behavior disorder that I passed around and is now incorporated into the diagnostic criteria for the disease it wasn't this varietal 1986 it's it's hard to imagine that in sleep medicine when they caught Topsy people who had a prior diagnosis of racing or and then you know someday die of something else they find on autopsy fifty percent six percent had diffusivity bodies eighteen percent had you know the particular findings diagnostic for Parkinson's and eleven percent had multiple systems atrophy which is it's kind of scary if you have written sleep behavior disorder to look at that there's another study showing that seventy percent of people with rim sleepy they report followed out for 47 years seventy percent converted to have one of these neurological diseases this is my VA fun that I actually have to answer if I can find it so we're talking about the autonomic nervous system even these are some of the things that can lead to these frogs who need to say complete Falls hip fractures April Federation constipation drug sensitivities delirium and then incontinence I say so these patients probably have higher prevalence of these problems at earlier stages the people with Alzheimer's or would it in the final thing when you think about these behaviors you can you know we have this at least in the memory clinic it seems like these patients are harder to take care of and sort of why might that be you know fluctuations from day to day hallucinations psychosis I think would be very stressful for caregivers there's not there I found that some just some very small studies one where they actually matched caregivers of individuals with either of those diagnoses based on their a relationship and the level of dementia of the info of the person thirty percent of the caregivers in both groups had depression however twelve percent of the Lewy body caregivers is known Alzheimer's caregivers have severe depressive symptoms early stage of caregivers for people with Lewy body dementia report higher levels of the stress related to the delusions hallucinations and anxiety that the patients have so I wanted to follow up a little bit with our patient is he was hospitalized in free of co settled increased weakness and Falls and he went to a nursing home he was a minute again that year with quote T IAS and got a right lower lobe pneumonia his men away with a sip of ventricular tachycardia and hypotension he was a minute again that year with them methicillin-resistant Staph pneumonia isn't it in 09 with a femoral neck fracture and went to a nursing home for rehab and then died in a nursing home too much later and so I mean this is kind of the natural history and all the complications that you see with this disease trying to manifest it in this one this one individual's life so the next thing I wanted to talk about with dementia drugs and will be body disease are they likely to cause help from harm you know we have you have aricept you know the land to mean have excellent patches yeah they do so the rationale for why they help is that the choline acetyl transferase is actually more depleted in the brains of people with Lewy bodies in Alzheimer's and that's what these drugs help with at the same time the receptors that respond to these drugs are relatively preserved so you actually have more potential for efficacy so there are two randomized trials or there are randomized trials that rivastigmine is an episode they're not had to they're not there are not head-to-head comparisons of these drugs in terms of what's formally approved the Nephil and galantamine and receiving are all approved for Alzheimer's where the stig mean which comes in oral or patch is approved for Parkinson's disease dementia also none of them have a formal approval for looking body dementia but but you know if you're going to go with what has the best evidence you would go with rivastigmine just because it's gone through the rigors of being approved for Parkinson's dementia but they all have a potentially work there was a randomized trial of noticing me they looked at from computerized cognitive assessment and the neuropsychiatric your inventory particularly this measure of storms course or delusions apathy hallucinations of depression which would be very important targets and these are the percent with greater than thirty percent improvement or that may outcome measure so that the most rigorous of the intention-to-treat analysis which is on the left revisiting me versus placebo so about forty-eight percent of Brittany versus about twenty-eight percent of the gazebo had a significant improvement in that behavioral different cognitive speed with the rivastigmine did improve macabre some bow and then kind of after the washout kind of and headed back for baseline there was also randomized trial de nem fazil with doses of 35 hundred ten milligrams and they use some some very familiar than a mental the caregiver burden scale and the NPI that like the other get to use and this is a little hard to see but has a different doses and I'm not being fire that what I can say about a de nefas ill and response is you get a substantially greater response than you did in the Alzheimer studies like for example on the mini-mental yeah maybe a half a point out of 30 with Alzheimer's and you know two or three times that with everybody patient so they may be more worthwhile in that population so treatment of psychosis and hallucinations do we have to always treat them no no so if they're significantly distressing to the patient or there's your order serious safety concerns to the patient the family or the professional staff who have to work with that person then there's a reason to treat first thing to do is discontinued a cholinergic drugs or any other drugs that might be worsening the metal status and then consider one of these cholinesterase inhibitor drugs if that doesn't work and the concerns are serious enough about the patient's discomfort or save you then you can consider an atypical neuroleptics drug if you need to you know be aware of the black box warning which is reproduced here increased mortality in elderly patients with dementia-related psychosis treated with these drugs increased risk of heart attack death and stroke and infections and pneumonia and you need to document that you counsel the family about this I had one other one other drug I found that when I was trying to see is there anything else out there and it's this stuff called yoku consign Oregon son it's covered under national health insurance in Japan for for treatment of patients it's like like most traditional medicines its a mix of herbs thank you chains and get new job the route here's their route 61 logo true licorice root and stems of gambler buying it was this kind of formula was published in the 1500s during the Ming Dynasty and it was initially for babies that are very fret up and there actually are four randomized control trials of this stuff with about 240 subjects what they showed was an approved NPI's for and improves subscales to delusions hallucinations education and aggression what about the same magnitude as the other drugs do improved ADL's no change in mini middle score so when they were not very many toxicities but the reported toxicities were hypokalemia and dysrhythmias would you think about the licorice root and the aldosterone axis actions of that that wouldn't be surprising that you get potassium in those operations but I mean this was as good in evidence as we see for a lot of other things in terms of treating the REM sleep behavior disorder there was a state-of-the-art review and sleep one of the sleep journals and looking at all the evidence and clonazepam by far has the most evidence 22 studies about 90% response rate melatonin and six studies with about a seventy-nine percent response and then paroxetine and pramipexole each had a few studies looking at them for that their recommendations were all in all the cities for evidence level course of case control or case series they give him a level B recommendation of 14 clonazepam or melatonin and in a level a recommendation was given to modify the sleep environment to reduce the risk of injury so such things as putting the mattress on the floor padding the corners the furnitures making sure that's not min class that the person is going to break if they thrash around removing dangerous objects I mean when I was looking reading about REM sleep behavior disorder there's a really interesting article is very dapper man demonstrating this device he rigged up himself time to thing around his waist that's sort of tied him to the bed that so I could fling himself out you know people really smart and creative how they deal with these things sometimes but so those safety safety recommendations so high side would you in fact what I find so i diagnosed this man with vascular dementia modified his risk factors what would what would we do differently for mr. mr. see what than what I did eight years ago china's aside yeah you know and i probably would consider the diagnosis of my body dimension to get every possible symptom of it i saw i would consider treating his executive function of herman depressive symptoms a certainty i would consider giving them like aricept or rib-sticking it might have helped and i would have considered probably first melatonin just as a safety and we've tried to get him off the olanzapine and really even more emphasized the safety measure since it was the hip fracture that actually it was the cascading man that went to his death so why it matters it's again second most common cause of degenerative dementia has a poorer prognosis has a high prevalence of behavioral problems it caused caregiver burnout and can cause that the individual to be interested to shun alized it has a high prevalence of autonomic dysfunction it puts you at risk for medical complications and falls it actually has a good response to treatment better than better than Alzheimer's disease this so there are actually useful things you can do so it's a final points so there's morbidity beyond just the cognitive decline the imaging techniques are very accurate we often don't usually actually need them to make the diagnosis but it can be used we have helpful treatments and symptoms and we need to anticipate the complications working with the patients and families Falls delirium well that's a point often when we're doing consultations and you know at with patients we have delirium or mystery delirium sometimes the template to say you know how loll is needed you really would prefer not to use how all these patients is it's you know you probably won a typical even though there's less data for delirium with these and you know be aware of drug times toxicities in distress on caregivers I think that's that's all right now yeah that's it any questions with a Japanese many kitchens he see available if you did it online I you know I'm a really pretty picture of an ad for it but yeah I mean I like to say I have a family member with this disease and/or you know really difficult behavioral and psychological symptoms and second to try it come on Cheryl mystic an apparent total circle that's not good oh yeah so yeah it is available yeah any comments make sure you guys my name receive me know so what next and you

Glenn Chapman

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