Looking Beyond Alzheimer’s Disease: An Overview of Other Major Forms of Neurodegenerative Disease

[Music] good evening everybody I'm glad to be back glad that you're all back for this third lecture of the session today we're gonna have a colleague and a friend of mine dr. Salvatore Espina who's gonna talk to us about a little bit about other diseases of the brain other neurodegenerative diseases of the brain beyond Alzheimer's disease that can produce that can lead to dementia and one of those clinical syndromes look like just to briefly review what we've touched on on the previous two lectures we've talked about sort of an overview of the neurodegenerative diseases how different disease processes that happening in the in the brain can lead to very different dramatically different clinical manifestations and through Alzheimer's disease that was our previous lecture we also learned that the same disease process of the brain depending on how it affects the brain can lead to very different clinical manifestations right the different variants of Alzheimer's disease so today we're gonna expand on that theme and talk about different diseases beyond Alzheimer's and and and my colleague dr. spin is gonna show you what these diseases look like in life and we're gonna take it from there so without further ado here's dr. spinner okay thank you good evening I'm very excited about being here tonight to talk to you about these diseases in the problems the day they raise for patients are also for their families and how has neurologists we try to sort them out you try to understand them and differentiate them one from the other so in terms of disclosure I received research support from the NIH and from other private foundations but I have no conflicts related to this presentation a brief overview have other things we're going to talk tonight so we're gonna discuss the prevalence so how common are these diseases in the general population and we're gonna compare the prevalence of different diseases to Alzheimer disease and then we're gonna talk about the most common ones so the focus will be on the neurodegenerative one so the one that caused by progressive loss of neurons in the brain and the one we will touch base on the Lewy body disease the body disease which is an alpha synuclein our party so this is a group of disorders characterized by the deposition of a protein called alpha synuclein there's two of them there's actually three of them the two of them Parkinson disease and dementia with Lewy bodies cause dementia there is a third unit that is called multiple system atrophy it's disease they rarely cause dementia but it came to about very very less than 5% of people then we're going to talk about the frontotemporal lobar degeneration z' we talked about a new topic a relatively new topic in neuro degeneration of aging as saying relatively new because it's actually we're talking about it for now for decades but it gets a little bit better formalized really just a few days ago so this is really breakthrough information and then we'll discuss about so what is the cars really dementia I see one disease for every person different than another person what there's more than one change occurring in the brain some more than one diseases at microscopic level that actually core together cooperate together to cause dementia to cause the symptoms finally we talked briefly about chronic traumatic encephalopathy this is one of the latest pathological diagnosis and it is related as you know as you probably many of you know to trauma and is a main concern is becoming a main concern among patients coming to clinic with the history of a head trauma so we talked about how this is relevant for the general population so you have been exposed to the numbers of the family disease epidemic so we have heard this very large number of in terms of problems and I'm a large number of patients affected what this means for this society and so the the prevalence of our my diseases in general population right now it's about almost 2,000 every hundred thousand people so 1800 people for a hundred thousand this is basically what our estimate is based on the estimate of the number of people that are been diagnosed with this disease so the about 5.8 million for instance in the United States this prevalence is probably an underestimate as you know because a lot of people do not actually get diagnosed never receive a formal diagnosis never see a clinician so while the total prevalence is this large number so 1800 the prevalence is actually different when we look at this toward the of the lifespan so if you look only people who are less than 65 year old is actually only 72 people out of a hundred thousand with Alzheimer's disease then the number tends to go up 65 to 74 and about 300 the largest number of patients with Alzheimer's disease are in age group 75 to 84 and then the number of people affected with Alzheimer disease actually start declining and declining for two reasons first of all there's less people of course this should by past age 85 didn't the expectancy in our countries around that that number but this is also the occurrence of other diseases the diseases of aging that can also play a role and so lead to dementia even in the absence of our Simon disease changes so we will start with this image and then I'll tell you why it could be wrong but so if we have to assign a single disease a single change that occur in the brain to the cause of dementia so in in a patient then we think that about 2/3 of all patients with dementia will have Alzheimer's disease so that makes our summary this is the most common form of dementia in about a quarter of patients with dementia we actually don't find a neuro degenerative changes in we think that vascular changes so ocular changes are basically small inputs of the brain according throughout life they may be responsive to some degree of cognitive decline that we see through life that at some point may turn into into dementia Lewy body disease which is the second most common form of neurodegenerative disease is actually attributed a number that is less than 10% so one in 10 patients that comes to clinical diagnosis of dementia will be diagnosed will be body disease as a primary disorder the frontotemporal dementia are relatively rare has always been defined as rare but we'll see that that definition really depends on what is the age or the population that we are talking about so if we think about the larger general population and the numbers the figures are indeed small perhaps 3% from several of the menses also condition that is largely unrecognized by by the clinician and so a lot of patients with this form of disease may actually be misdiagnosed with having other forms of diseases without summary disease been the number one but we will see that in other age range from temporal dementia become instead an important cause of dementia finally there are other diseases that are rarer they may be responsible for for small proportions of cases so we'll start with Lewy body disease again this is a single entity pathologically because essentially is caused by the deposition of alpha-synuclein and the true in the brain in the two major diseases are Parkinson disease in dementia with Lewy body so that you want to be careful in this distinction of Lewy body disease versus dementia with Lewy bodies is essentially not to way of saying the same thing so Lewy body disease is what happens in the brain and the consequence of Lewy body disease can be either Parkinson or dementia Bali's so the most common of these diseases is Parkinson disease this is a condition that is relatively well known by the midi general population it's a disease that is characterized by very easy to recognize symptoms and in science you might have heard about resting tremor so a tremor that hexane while the patient is not actually doing any movement it actually may improve when the patient is moving for instance they reappear once that movement is stopped patient tends to become very rigid very stiff usually the stiffness is a symmetric meaning one side of the body is more stiff than the other this is important for the clinician because it's more likely to be caused by Parkinson disease than by other diseases they look like Parkinson but they're not patient with Parkinson the brady kinesia this is a term that essentially means slow movement so slow movement is one of the most cardinal feature of parkinson's everything is slowed down and it's not just movement it could be also walking I could be turning for instance it's also thinking so the slow thinking of the Brad if Renia is also a characteristic feature of Parkinson that is postural instability that usually leads people with Parkinson to fall to be prone to falling and then again this isometric concert is a patient that has one side of the body either the left of the right more afetr than the other is very indicative at this condition and the most indicative feature clinically is probably the responsiveness to levodopa so liver dhaba is a medication that can be given to patient with Parkinson disease patient will have a true Parkinson usually tends to have a very good response to this to this drug the lasts for several years and it can improve dramatically their symptoms when this response is not there then is when we start being concerned that this is probably not Parkinson disease but another instead another condition the prevalence of Parkinson is very high so in in people who are in the fifth decade of life it's about fourteen dividuals out of a hundred thousand who already developed this condition and then in people who are actually very old their prevalence is definitely very high 1900 so for even had an Alzheimer disease again Parkinson disease in elderly is also often unrecognized sometimes patients people become just a little bit slower they start developing a shuffling type of of gait their balance tends to get worsen very often this is attributed to vascular disease but actually neuro pathological studies have shown that this is Parkinson disease just showing up very late in life and there are other things that is not that is not very often told about is that Parkinson disease is not just a movement disorder but 30 to 40 percent of patients with Parkinson disease will develop dementia toward their life and the risk of developing dementia is higher as long as the patient sleep so so also increase basically with aging patient with Parkinson's can live many years in essentially people that will survive this diagnosis for more than 20 years have more than 80% of chances perhaps according to other groups even up to a hundred percent chances of developing dementia so why is dementia with Lewy bodies difference than Parkinson's so the distinction is really based as dr. Lunada was saying before on what part of the brain is affected first by the disease so traditionally in Parkinson disease is the most coral so the lowest part of the brain when it is attached to the spinal cord it is affected first by the disease and then the disease from this portion of the brain start moving toward the cortex so the brain itself and so from movement changes we are the onset of cognitive changes in dementia with Lewy bodies the disease instead has a very high burden of pathology already in the cortex since the very beginning and that explains why cognitive changes come very early usually this distinction is considered technically at least in the research setting to be a year so if patients is currently normal for the first year of movement symptoms will be given a diagnosis of Parkinson disease if instead the cognitive changes occur during the first a year is sometimes prior to the movement changes then it will be given a diagnosis of dementia with Lewy bodies the distinction is important for many reasons to know what can happen later and also because the management of patient with the two different conditions actually different meaning we use different medications and we have to be more cautious with the use of one of other medications according to what is the correct diagnosis to give you a sense of what a patient with dementia with Lewy body disease experience there is usually a complaints about attention a deficit of attention a deficit with task execution there's also profound visual special deficits of patient have difficulties with moving in the space they get disoriented but also have difficulties with understanding spatial relationship there is the presence of characteristic cognitive fluctuations these are like dramatic changes in the level of cognitive functioning of these patients that can occur even within a day or from a day to another so the specialist may look very somnolent inattentive unable to follow conversation early in the morning and then all of a sudden look much more bright and much more attentive a few hours later Annika can go back to this status of I per some confusion in attentiveness visual hallucinations are very common a probably one of the symptoms that clinicians pick up very soon as indicative of this condition visual hallucinations in dementia with Lewy bodies but also in Parkinson are typical patients experience the presence of somebody of a person or shadows for instance in the room very often behind their head what we call extra camp in hallucination meaning these images these things that are not there but they perceived as real are often somewhat outside of the visual field they cannot be they cannot be followed so the patient will turn they have looking at the shadow behind and they will be gone already even before he can realize about the boston body or not sometimes the elisa nation's evolved scene people sometimes involve seen faces or little animals they may be more or less complex some of them are perceived as frightening some others instead are perceived as non real and sometimes even somewhat peaceful some of these patients report for instance seen deceased relatives as a result of these hallucinations well sometime they may be very very bothering and difficult to to treat but conditions share a phenomenon that's called the REM sleep behavior disorder this is essentially another way of talking about the dream enactment so when we are in this particular face of sleep REM the one where we have rapid high movements that can be seen underneath the high lids we usually dream in so evolution istic aliy we have a system that basically makes us completely paralyzed so the the muscle tone is completely eliminated so we cannot move we cannot fall our dream and we are prevented from the danger that that can that can trigger so patients who do have a dream enactment are at risk for alpha-synuclein all but almost all of them and these are very typical in patients will be body disease but it also be a risk factor for for Parkinson disease eventually this the motor science of Parkinson disease develop in all patients with dementia will be bodies but tends to be less typical so these patients usually have less tremor but appear a lot more rigid for instance so in the prevalence as I said before is about 7% there are other symptoms that we think are characteristic at least indicative of this class of diseases they are personally neuropathy so the autonomic nervous system which is the part of the nervous system that control all the activities that we don't have to think about so how to keep it blood pressure high all the time regardless of whether we are laying down on bed or standing or how do we keep our body temperature constant regardless so what's the temperature outside so all of these functions are done without us thinking but these parts of the nervous system is heavily affected by the deposition of alpha-synuclein our body there is usually a referred degree sense of smell which weather is shared by other conditions so it's not only specific of this disorder seborrheic dermatitis which is an inflammatory condition of the skin usually an is a response to increased secretion of severs is a risk factor for the alpha-synuclein apathy so there is a higher incidence of of this disorder in people who are serviceable right dermatitis and then often patients with arsenic in operty suffer of a severe anxiety depression and then we know about the diminished tone of voice the chris official expression and very often also of delusional thinking so the dissolution may be of all sorts the paranoid delusions for instance or also other type so this case the scheme again show you what I was mentioning in terms of you know that the deceased look like based on what parts of the brain is involved and usually in Class A Parkinson disease no D D medulla is the first part of the brain it is affected so this is a st. a center of autonomic regulations and then progressively deceased start involving more rostral portion of the brain the large centers here that control mood for instance of the anxiety the depression at this point xn and then when structures like the midbrain had involved that is when the braddock images of the slow movement the rigidity eventually is manifested eventually the disease spread all the way throughout to giving rise also to the cognitive symptoms and D in the dementia so again in in dementia with Lewy bodies this phase is actually seen earlier in the disease process and the disease may start more in the in a central portion of the brain and actually spread in both directions both verses cortical area and also eventually more cordially so giving rise to the motor symptoms actually later so this slide just match basically the different stage in the manifestation of the symptoms of Parkinson's disease as really a consecutive involvement of different regions of the brain as I've shown you before and then from the point of view of the neuropathologist this is a section of the midbrain so the part of the brain is really connected brainstem with the brain with itself with the cerebral hemispheres and its structure here that you see is called this substantia which means it means the black substance it's an area of the brain it is enriched with neuron that produce dopamine in there go also the hollar the black color which is like a bio product the synthesis of this molecule so the loss of these neurons that the the neuronal death caused by Parkinson disease will cause the complete disappearance of the substantia and that is why we also use levodopa as a main drag in order really to replace what has basically been taken away by by the disease we talked about Lewy bodies how these are Lewy body diseases and so these are Lewy bodies so these are bodies as they look like on a histological staining and we call em a toxin or seen it's just a way basically that we can stain tissue either in red or blue color and a Lewy bodies will look like this round structure here there is one this is another one here usually surrounded by this large aloe and then if we stain the tissue with antibodies directed against a specific protein in this case it will be alpha synuclein we can see that these structures indeed are made of alpha synuclein so confirm it and indeed these are Lewy bodies so this is how the neuropathologists eventually will make this diagnosis on the brain when examining the brain post-mortem alright so we moved out to the to the next group of of dementia in terms of incidents so we're going to talk about the frontotemporal lobar degeneration this is a very interesting group of disorders and you can see that the name essentially is already saying what is the most Cardinal features of them so it's really the involvement at the preferential involvement of the frontal in the temporal lobes of the brain I give you here a picture of the brain the brain post-mortem so this is the frontal lobe of the brain this is the temporal lobe and then you have the posterior regions of the brain the parietal portion of the brain and your occipital lobe all the way here posture so you can see that there is a striking difference in how on the extent of shrinkage really technically of brain tissue in the frontal portion in the anterior portion of the temporal lobe you see it is opening up a little bit you can even see more deeper structure here while this normally would appear would not occur while the posterior regions of the brains are better preserved so these are a strange disease even though cause dementia does an effect the brain has a whole effect preferentially this anterior portion of the brain as opposed to the posterior ones so these are very all the diseases and the first description of this very peculiar way of causing dementia was given by Arnold peek back in 1892 so pick was a pathologist working with with Alzheimer and it basically shall identify this very peculiar a set of cases in which the brain just didn't look like an Alzheimer one so there was not in atrophy so a reduction in the volume of all regions but the these two regions in the frontal and the temporal lobe were selectively involved while the rest how the brain was looking pretty much unaffected it was actually Alzheimer disease that defined the term epic disease and he did it because when he examined the first cases of this brain observed that were not nudity plaques and you have heard about nudity plaques from the talk from dr. Ernest and so they were not the classic features of Alzheimer disease so this was indeed not cases of Alzheimer and instead as what is very rounded and silver stained structures that he called big bodies in honor of Arnold peak who actually had found the disease so the term peak bodies is actually created by Alzheimer and the name pick diseases also are picked by by Alzheimer disease to say that even nowadays so many years later the turns peak disease is used as a synonym of frontotemporal dementia so for the clinical presentation and also as a synonym of frontotemporal lobar degeneration which is the process that happens in the brain of people with this type of disease but this term is a this association is actually improper so we will see in the next slide the peak disease is only one type in not even the most common type of the frontotemporal lobar degeneration so although many clinicians still use it in general tell me this term still used as a synonym Oh from the temporal dimension the two things are actually are actually distant so how often is frontotemporal dementia so the proportion of cases is actually very low so compared to 18 ended for a hundred thousand cases of Alzheimer disease on the same population of a hundred thousand there's probably no more than 50 cases of FTD again this number may be strongly under estimating the real prevalence this disease is difficult to diagnose sometimes and the clinicians are less exposed or even less educated in in in training so the number may be a little bit higher but definitely the proportion is much smaller than that of Alzheimer disease however if we look at the different age ranges then this scenario changed dramatically so by age 65 frontotemporal dementia is actually as common as Alzheimer disease so somebody has cognitive changes behavioral changes and presents to to a memory clinic in its 65 year old it's actually the one to one chances of having either Alzheimer disease or frontotemporal dementia if things get even worse if we think about even younger stage some people who are less than 60 years old we think nowadays that frontotemporal lobar degeneration actually more common than our semi diseased as causes of dementia does exist in the elderly it does but it's not so common and perhaps the prevalence will be around 3% so we're gonna talk first about the syndrome so you remember the distinction in dr. Lunada have presented since lecture number one one things are the syndromes so the symptoms the reason of the patients come to the clinic another thing is finding out what's happening in the brain so let's look first at the syndromes so under the umbrella of frontotemporal dementia which is the clinical presentation of people from the temple of a degeneration there are at least three canonical syndromes one it's called behavioral variant frontotemporal dementia because of the predominant behavioral of aspects of the clinical presentation which are actually much more severe than the cognitive one so patient behavior is much more affected in memory of other other cognitive functions and then there are two variants that effect instead language so we call them the language variants of frontotemporal dementia one is called semantic variant and the other one is called nonfluent variant you know once again from the temporal lobe of the generation give us again a confirmation of that on the fact that is really where the disease is mostly causing damage of the brain that will lead the clinical presentation so in patients who have profound atrophy of the insula the cingulate gyrus the prefrontal cortex the clinical presentation will be there too behavioral variant FTD in patients who have anterior temporal lobe degeneration the clinical presentation will be that a semantic variant PPA and in patients will have a predominant degeneration of the structures that are related to language mostly language production the clinical presentation will be there are nonfluent variant frontotemporal dementia so I'm going to tell you first about the behavioral variant FTD so these are patients who manifest very early in their disease course some very prototypical symptoms in order to make a diagnosis you need at least three or the other first six criteria so patients present often with profound disinhibition this means profoundly inappropriate behavior which usually translate into being totally unable or no longer basically able to comply with standard rules of social conduct they otherwise may present with profound apathy or inertia that means that they will be losing interest they will be losing any initiative on doing things this can be people who are very socially engaged very active very productive and then all of a sudden start seeing all of the interest completely in fading away so what what before was very important getting up in the morning going to work paying bills interacting with the family all of a sudden become not interested absolutely not necessary together with this there is the development of changes in emotion regulate this goes on but sense there is a progressive difficulty in understanding other people emotions so an absolute inability to understand people sadness or happiness or hanger or frustration this track is also associated with a inability to understand or to act in a way that is compliant to the proper emotions so to inner emotions officials for instance will no longer feel embarrassment or the longer feel sadness themselves there is often the insurgence of new behavior that tends to be very preservative meaning they happen all the time like a compulsion type of behavior it are very difficult to manage in they ended up using basing the largest amount of time of this patient during the during their daily life so again they no longer do any work for it so they no longer interact with the family but they may be a very interesting to anyone new collections for instance of item or another type of activities some of them may actually be interesting like for instance development of new artistic abilities but often that the activities are actually totally futile I don't don't lead to anything that is this productive there is I / orality which basically is an increased interest toward food especially for the high calorie or or sweets but is also an increased activity of placing objects in the mouth can remember a little bit of the behavior of kids like in the very first year of life so that is the type of regression that we often see patients will stop their mouth with a lot of large amount of food for instance sometimes make it difficult for instance to to swallow what they would attempt to swallow an edible objects and then in terms of the cognitive profile a neuropsychologist is usually faced with patients that can no longer function in the society in the regular life but actually tends to perform really well or relatively well on the classic kinetic test that is given to screen patients for our family disease for instance their memory remains pretty good for a long time and so they usually tends to do much better on cognitive testing then it's compared to harshly how they functioning in in real life beside the criteria we also helped by again the imaging studies as in the diagnosis as I've shown you before and also by genetic that sometimes can make the diagnosis clear and definitive so why emotion why is emotion this central piece of the clinical manifestation that because again this areas in the brain like the insular bilaterally in these cingulate gyrus which are really the structures of the brain it to be used in order to understand ethical values morality what is good what is bad is my action going to harm somebody did I do something it is inappropriate so all of this action what is important now all of this activity of the brain all of this structure in the brain that are doing this even when we don't think about it does that the one that are affected first and early in this in this disease so these are just some examples of emotional deficits but the list that really can be very long so this patient's big lose concern for loved one illness they sometimes develops a cruel type of behavior toward children toward animals to all elderly very often this can result into issues with law for instance there are they are tends to be prone to to rude comments to others and more distinctively there is this loss of interpersonal space again the entire scheme of the general rule of social conduct that we learn and not rule to child will get somewhat lost the disgusting behaviors as as described here is again secondary to the generation of centers in the brain that tell us what is dangerous so we all know that is dangerous for instance to look for food run away in a trash can this this this immediate stop sign is red flag is gone and so is together unfortunately with the IP reality may push patients with this type of disorder to for instance look for food everywhere to steal food from other people plates and there's also some changes in the way the brain also interpret external stimuli including including pain so during this presentation I will show you a few videos these are from patients a research participant of our clinic they have all provided the authorization for the distribution of these videos for educational purposes so so this is a gentleman that was very active and very productive in his life and very close to his family whose behavior changed as a result of behavioral variant FTD we never go the first Sunday of the month because that's communion and our communion you walk down front and as you walk down the aisle everyone was greeted and back rubbed and asked where they were from very disruptive [Music] so you see there's a behavior that we would expect again on a kid so but also motivated and triggered by what we call utilization behavior so if stimulus is in front in this case will be like the hair the person city's just in front of them there's almost this magnetic attraction in the complete loss of the social conduct rule rather should have impeded them here I give an example of the rhetoric behavior the compulsion developed by this patient this is where Bob keeps all his possessions his coins and his wallet and he always has a pen in his book and then he keeps his figures for his aunts and he records all of them and keeps him down by the day of the week and how many he killed and then they stay here for quite a while and then he also has all of his napkins that he likes to save even if they're used or not and he always has some in his pocket that he keeps and a little stash of candy [Music] and so again a very meticulous activity they can occupy a large amount of hours but it is of course futile so we will now to the language variant of frontotemporal dementia so again I told about semantic variant in nonfluent variant frontotemporal dementia so what are they so this concept of primary progressive aphasia was put in place by marcel mouseau l'm back in 2001 Marcel Muslim is one of the most famous behavioral neurologist in the planet he and he was the first one that described beautifully this syndrome primary progressive aphasia this is a condition in which language is the main area that that generates for the first couple of years in the disease process of people with the generative disease so these are neurodegenerative diseases these are not stroke this is a similar to a twelfth Simon so caused by progressive loss of neurons in a Treviso shrinkage of the other brain in which language is a predominantly fetter than everything else is almost unaffected list for the first couple of years so later Marilu gone attempt Eenie has actually mapped the three more commonly known forms of primary progressive aphasia and again you can see that is really which part of the brain it is affected they determine what type of primary progressive aphasia patients will have so the one that relates to frontal temporal dementia the one in blue semantic dementia when the degeneration is mostly in the anterior temporal lobe right here and then in green the nonfluent variant of primary progressive aphasia in which is the posterior portion of the frontal lobe but also the insula or the brain that degenerates so these are really the two a PPA syndromes linked to frontotemporal lobar degeneration there is a third form of PPA which is called logopenic variant you may have heard about it from the talk or daughter and a son so this is one of those focal forms of Alzheimer disease or logopenic variant PPA is almost invariably associated with címon disease but the other two are actually two forms of frontotemporal lobar degeneration so in semantic dementia again there is a profound in early degeneration of the temporal poles we have two of them one on the left and one on the right in semantic dementia is essentially caused by the degeneration of the anterior temporal lobe in the language dominant cerebral Hemisphere so language is a lateralized function in the brain meaning is only it's predominantly on one side of the other brain and in the majority of us in the majority of the population is confined to the left side so if the left temporal Pole undergo neuro degeneration semantic variant PPA develops the most striking features of this disease is impaired confrontation naming so what does it mean confrontation naming it means basically showing to somebody a picture or an object and simply asking for names so the very first symptoms is the progressive loss of name of the ability to name things so this is called anomia also neurologically but in this particular condition semantic dementia is just it's even more than just the difficulty with the name is mostly actually the loss of the word meaning so when a patient cannot come up with a name it's not because he knows very well what it is what that object is it just cannot retrieve the word he's actually lost the concept of the specific origin or that specific word and this becomes more severe initially early in the disease process for words that we use less so things that are more common are the last ones they would disappear names that they were use more commonly will be the last one to disappear names or words that we use less frequently will be the first one instead to disappear together with this loss of meaning for words there's also a loss of meaning for objects so sometimes patients are presented with an object and they're unable to to tell what it is or what is the function that there is the development of a new sentence are called surface dyslexia so this has little to do with the class II dyslexia that we are used to to hear about and it's instead the phenomenon of enunciation of specific words when these are phonetically irregular so what is a word that is finagler phonetically irregular is awarded basically in order to pronounce it correctly you need to know how this word sounds you cannot just rely on the on the letters on the screen so this is a word that's pronounced carnal but you really have to learn that this is carnal and not : l so a patient with semantic variant PPA might find himself actually pronounced in this words as : l as opposed to carnal and this is actually sindelle it is more commonly seen your language there have you regularly irregular phonetic words my language for instance Italian is very few of them almost none so surface dyslexia is very difficult to assess just because every letter is pronounced essentially the same way English is the perfect language instead to to assess this type of this type of problem so if this counts in value is another second English a second language you want to be a little bit careful so there is usually spared repetition so even though the patient may not know what they're saying or what is the meaning of the words they're actually able to repeat even a very long sentence so they may not know exactly what's in it but they can repeat it without mistakes and usually grammar is also spared so they don't make profit making mistakes either when talking they usually become very verbal so one of the typical characteristic of patients with semantic dementia is their verbosity they're hyper verbal and this is one of the reason that we call this forms of PPA a fluent aphasia so it's fluent for two reason there are not difficulties in the enunciation Awards is the words meaning that are lost and secondly there is also this increased production of our speech that is sometimes a sign so these are I also example in which we can elicit this disease in in the in clinic so we can ask patients for instance to draw animal in here we start seeing that no dog is drawn overall in a okay type of fashion and then we move to a cat and you know we can still recognize you know the structure of an animal you know with the head and four legs but for instance we're missing like characteristic features like the ears of the cat they're definitely different than the ones dog and then we go to less frequent draws like four is instead of a bird and he started looking like something that still has wings but it doesn't really look like a bird and if we ask for a fish it doesn't look that different any more than then actually a bird so one thing that pushes to with cemented variant is they were always you that would tend to use especially at the early stage of the disease how old it belongs to the same category but it's just more frequent so if we show a picture of a lion for instance you may not remember lion but you can tell it's a cat then the disease progressed they would just the answer may be just it's an animal and then this is progress and then at this point there is nothing else that can be linked to that specific image so I'll show you here an example so this patient is presented with pictures it is asked to name them [Music] some kind of a bad what do you do with it [Music] but that you know what you do with this [Music] it looks like some sort dog the patient not uses brain to identify the correct name is gonna look like in in this category of animals but you know all low-frequency animals that disappeared the snail is probably disappear early and what's left is a dog so it's an animal it gotta be a dog right here an example instead of a patient's having difficulty with recognizing an object this is a tennis ball yellow yellow something or other what do you do with it I don't play without oh oh I've seen it really hard so maybe put down bring little kids up seriously the patient again is unsure about what it is he call it with a collar and said then with the proper names kalos tends to be retained for a longer time in this disease then another interesting phenomenon from us you see things get a little bit clearer when she can actually feel it when she actually touches which using other old memories let's the information read how does that feel so that feels like a tennis ball so now that she touch it the information actually comes back but she cannot longer just rely on looking at the image of the tennis ball so this is interesting because when he affects the non language dominant hemisphere which more often is the right side so the right temporal Pole they actually present a little bit differently any present more similar to a behavioral variant FTD so behavioral cinders are a lot more evident if the right temporal Pole instead of the left is affected it's just because the sentence or language are less prevalent that's the only reason essentially so there are however other features so the temporal Pole retained and semantic information so the meaning of the information of phases so this patient Santa's can recognize acquaintances friends but they have difficulties recognizing a face that is symbolic so if you show them a picture of Marilyn Monroe you can say it's blonde woman but doesn't know what I represent the same for Ann Steiner or anybody else so we show them pictures of famous people to understand if they can give us more information than just you know the image the physical detail what does it represent they tends to have an increased interest toward the words in word games this is probably a release type of phenomenon so the left temporal lobe it's now left alone because the right is degenerating so it cannot do well it would overdue that's what we think he may happen so these people becomes very interested toward games that involves words they start reading for instance obsessively billboards or or car plates and again the word search games become very very significant sometimes of that many hours a day or day it has to become rigid in terms of personality very strict a very rigid schedule is always the same should not be disrupted again with a lot of stereotypical behavior and often look cold distant sometimes this can be the very early sign of the disease it can lead to interpretation like an antisocial type of behavior they can translate into a lot of problems in the work environment in the family so raising a lot of issues before the correct diagnosis is actually made another feature that we often see in patients with a right temporal lobe FTD is IP religiosity so they become patient may become much more interested into spirituality sometimes they embrace new religion sometimes the spiritual is totally new so when people who never express this feeling before and it become again over imposing so pervasive so it's not just a new interest okay but it's something that become predominant the only thing that these people may be interested about during during their day okay so this said the characteristic feature of semantic variants so now we're going to move to the second type of language variant frontotemporal dementia so the nonfluent variant so as the name says this is a condition in which the most distinctive problem is that of a nun ceding speed so actually talking so being able to translate this idea of wars that we have in our mind in a word that can actually tell people there are always a disruption also the linguistic rules so usually there is a profound agrammatism so a lot of grammar mistakes both in speech and in writing so like for instance or conjunction or problems with with the use of verb for instance or with spelling these are very very common most importantly again the speech become very effortful very housing and there's a lot of sound errors a lot of distortion that can be perceived very very easily interestingly the comprehension of a complex sentences is actually impaired it's very difficult for this patient to understand a very long and complex sentence though in in comparison with the semantic variant patients if you actually give them one word at the time there will be knowledgeable of all of them so the knowledge award is actually fully retained and so it's also the knowledge of object so I'll show you this woman and you know in the first part of the video she's gonna be asked to reproduce some phoneme a so some single sounds so part first then tap and then cut in the say those three sounds one after the other one this is gonna be challenging with the words a little bit more complex like artillery for instance and you'll see how this is difficult and and the changes the mistakes that she'll makes that are always different one from another me aren t roller our corollary are terribly aren't are very good there's a very difficult ones they're made to be difficult so again she has a full knowledge she never asked what is that so while a patient semantic variant may but she has this difficulty in enunciation so again these are the three prototypical types of frontotemporal dementia so this is the standard let's say like the canonical Iwan under the umbrella or for the temporal dementia is either behavioral variant semantic variant PPA or nonfluent variant PPA there are however at least three more syndromes that we also refer we Dina rounded the umbrella frontotemporal dementia this is because often in these syndromes patients will manifest some of these centers that we have discussed before so some behavioral changes for instance and also the diseases in the brain that cause these syndromes here are shared somewhat by diseases that will cause behavioral variant FTD so this is why these three additional syndromes are placed and they need the same umbrella okay so we're now moving from three syndromes to a total of six syndromes okay so the first one is frontotemporal dementia with motor neuron disease the second one is progressive supranuclear palsy syndrome and then the last one will be corticobasal syndrome and again every time there is the word syndrome it means the symptoms okay not the disease in the brain so the first one frontotemporal dementia with modern urine disease this is one of the most devastating diseases neurodegenerative diseases that we deal with and patients who had to deal with motor neuron diseases are diseases that affect the neurons that are somewhat directly or indirectly connected with our muscle and so when they degenerate they will cause muscle weakness and muscle degeneration the most common of these diseases is als amyotrophic lateral sclerosis also known as Lou Gehrig disease because Lou Gehrig was one of the most famous patients affected by this condition so about 10% of patients with frontal temporal dementia will develop ALS later in the disease course and most of the patients with ALS develop some type of cognitive impairment when I say most I'm referring to more than 50 percents about 60% for some of them this will turn also into dementia sometimes that dementia does not develop because of the relatively short duration of survival in patients with ALS with the average of survival being of only 3 years the second of the syndrome is progressive supranuclear palsy syndrome also known as Richardson syndrome this is that this is the look a lot like Parkinson disease but has some distinctive features that make it noticeable for the clinician relatively early so these are a very early complaints of recurrent Falls so these are usually patient of the very first symptoms is a fall followed by another fall and again by another fall these are usually initially in a one fall every three months then become falling once a month falling once a week falling several times during during the week fall so you not triggered by by particular stimulus so initially there there tributed to tripping to an object by instead it becomes very clear that these problems really with with balance there are changes in a movement are very typical patients are unable to to to move their eyes in the indeed for the direct direction of space this is something that can happen very early in the disease but sometimes is a little delayed and it's more severe for movements that are vertical so vertical high movement are more affected then then the horizontal movement there is rigidly like in Parkinson but it's tends to be more axial so instead of being one arm or one leg that is more rigid than the other which is usually a good sign for Parkinson meaning this is probably parties we can be treated it will last longer patients tend to be rigid mostly at the level of their skeleton or their neck are more likely to have a progressive supranuclear palsy syndrome which is a disease that usually had the reduced duration in no treatment at this point so the most distinctive feature is really the lack of response Ness to levodopa so even in spite a large doses of levodopa there is not improvement or the motor symptoms cognitively this patient tends to be mostly dis executives so they have difficulties with task solving tasks understanding so there is increase the impulsivity and there is a characteristic disruption of the sleep pattern specials are unable to reach deepest stage of sleep is as if they were in a shallow stage of sleep essentially overnight which make them also Lesko natively performant the last of the syndrome is corticobasal syndrome so this is a condition again also similar to Parkins a similar to Parkinson in the sense that is often a symmetric so the manifestation actually are more obvious on one side either the left or the right out of the body and but the features are different than it then Parkinson so there is rigidity but it's also dystonia dystonia is abnormal muscle tone regulation that involve the tone of more than one muscle so a series of muscle usually they regulate the position of a specific joint in space so it can be that the rest for instance it can be at the finger it can be the arm a different position from the shoulder to the elbow down so the patient will tend to acquire a position of their arm that is abnormal and that is closer to their chest or not functional that is usually myoclonus which is the precedence of jerky involuntary movements they may be either spontaneous or sometimes triggered by for instance tactile stimulation patient developed in coordination of movement that involves both the mouth so the oral apraxia and limbs so the arm so if they have to reach for an object reason they overshoot or they will be unable to to execute the series of action that is the proper for the goal that they are trying to achieve there are other features that basically tell us that there are other parts of the brain involved we call them cortical sensory deficits among those essentially there is a state of gnosis which is the inability to recognize an object just from touching it even without looking at we're all able to say this is a probably cell phone or this is a key but this is an ability to get lost the disappeared very real impressions with CBS the same thing the patients are unable for instance to tell what type of numbers or letter we are pretending to write on their on their palm so this ability to see with ice close essentially just relying on sensation is lost early in the disease and then there is a strange phenomena is called alien limb phenomenon as you can see is basically a phenomenon by which the limbs usually an end or or an arm starts moving on its own so while the patient is not planning to execute that action and action for instance like arm levitation they aren't dust levitate while patient is doing something completely different sometimes the inner limb phenomenon is oppositional meaning the arm that is affected may try to oppose the function of the other ones and as the other one is actually the good one meaning the one where like movement is still retained and but is unable to actually execute correct movement because of the allele in phenomenon from the other side so I'll show you a video this is a patient with a cortical basal syndrome oh also has nonfluent variant PPA so you will see movement abnormalities while a language is tested so you will recognize the deficit on nonfluent variant PPA in in the background you will also see the movement disorder related to corticobasal syndrome could you say five times for me right here artillery Tillery artillery so you can see that the right arm is held on a dystonic posture you can see the position of the arm overall position of the finger the wrist is not normal it's not as not natural and then the left arm is moving a lot and you will see Lashley at some point will start doing things that are actually not in the volition of the patient in a positive toward the right side great well done should we try another one impossibility very difficult one impossibility catastrophe so that's why a lien lien because it's really like an art unarmed really that move on its own it almost has a mind of its own so so we are now seen all the six cardinal syndromes that are under the umbrella frontotemporal dementia so in this slide that you've seen before you have on top the six different clinical syndrome within the spectrum of frontotemporal dementia so behavioral variant FTD semantic variant PPA nonfluent variant PPA and then frontotemporal dementia with motor neuron disease the ALS type corticobasal syndrome this last one that we saw and progressive supranuclear palsy you may remember the one with severe high movement abnormalities so in the lower portion of the slide instead we'll see the causes of this syndrome so this is what we actually see in the brain so what is in the brain that is causing the symptoms up here in the slide is color-coded in a way that she based on the color you can see how frequent is that that syndrome is linked to each and every one of this pathology so this are all distant process that can happen in the brain each one of this is a distant thing the distant entity that can be seen by the neuropathologist under the microscope and it can cause one of this syndrome so for instance if you look at semantic variant PPA you can trace a semantic variant PPA is most commonly caused by a single pathology that is the temporal lobe or the generation with tdp-43 this is the name of this protein in the type c actually so not the other ones but most of the type c you can also see that progresses of a nova palsy syndrome is almost always caused by PSP pathology so again this is the syndrome but can also be caused by other condition like corticobasal degeneration or peak but the majority of cases of PSP syndrome will actually have PSP pathology you can see that why in some cases this association is almost one-to-one for instance a patient of modern neuron disease is probably gonna have like a 99 95 to 99% of the times is gonna have tdp-43 pathology in the brain so for some of this clinical pathological correlation the correspondence is actually pretty strong so a neurologist King gas in a very educated way what the neuropathologists is going to find eventually at autopsy this is important because in the end when we use medication both to treat this condition or to prevent this condition we actually need to know what's happening in the brain regardless of what the symptoms are so the symptoms are useful just to recognize the process that is happening in the brain but our ultimate goal in clinic or also for clinical trial purposes Asha to understand what's happening in the brain is this a dysfunctional tower is this a dysfunction of TDP because this will be very different so we would like to treat them very differently so you say well for some of this condition this association is almost one-to-one here here in here for other conditions and BBF TDD behavior variant FTD syndrome is probably the worst this association is extremely difficult so almost all of these conditions underneath this pathological changes in the brain can cause behavioral variant FTD and it gets even worse because if we add Alzheimer disease to this picture as you already know from the lecturer dr. Nason our Simon disease can also cause frontotemporal dementia type of clinical manifestations so explain about 1/3 of all cases of cortical basal syndrome so if patients are very young for instance in they have corticobasal syndrome they often tends to have Alzheimer's is that the corticobasal degeneration you can also cause some cases to semantic variant PPA and it can even cause some cases so behavioral variant FTD frontotemporal dementia again in the lateral daughter nasaan you saw so-called frontal variant of Alzheimer disease so it gets very complicated so I'm gonna show you how this pathologies look at the microscope briefly but just to give a sense also historically how we ended up here so we're going to start from the group of the FTL D tau we call the deceased our patties so basically disease linked to tau you see the pic is one of them my only one of them there are many others so up to the beginning of this century we actually thought that frontotemporal dementia for the temporal lobe of the generation in in towel we're somewhat synonymous so they're almost always all the FTD cases were due to tau the position though some of these cases behave differently than expected under the microscope we actually learn only recently so starting from 2006 when tdp-43 was discovered that the tawa bodies are not a majority of frontotemporal lobar degeneration but they represent only up to 40% of cases so then they're divided in terms of the pathology based on how they look under the microscope so these are the big bodies that harnell Peaks already at the beginning of the last century they looked the same even today with stained with tau this is a tufted astrocyte so these are the inclusion of tau protein within the most proximal process of astrocytes are not neuron about astrocytes other cells depending the brain so when a neuropathologist see this he knows that this was a case of progresses of a nova policy even pathologically and this is an astro CITIC plaque look similar to the neritic plaques that you've seen for outside but it's very different again here again the deposits are in astrocytes and not in neuron in this time is also the distal processes of the astrocytes that are involved by the deposition so we move now to the FDL dtdp so again today before III was only discovered in 2006 but we now know that 55% of cases left eld are caused by the deposition of this protein and you know since you can since now we now know that it's really now what parts of the brain are eventually affected by the deposition of this protein as opposed to creating this one-to-one Association syndrome versus pathology you can tell that the name is change right so before we have progressed Renuka Parsi pathologically just because of the most common problem happening the brain in patients with progresses over an ogre past according of basal degeneration a lot of patients with corticobasal syndrome so now that we understand that it doesn't really matter it depends on what part of the brain are affected by this condition the classification of tdp-43 pathology is much more simple and less exciting right is just type a Type B type C type T so we no longer associate a specific name but again this looked different at the microscope so in type A you see the shortener eyes and also the presence of inclusions both in the cytoplasmic neurons is sometimes in nuclei in type B these inclusions have very speckled feinted granular usually the nucleus of the neurons is affected doesn't have normal TDP staining these are lower motor neurons like in ALS so this is the appearance of motor neurons that are degenerating and the would cause eventually muscle weakness a muscle waste this is probably the most useful for us so when a neuropathologist see this figure so the president is very long this trophic knee right staying with GDP 43 as a 95 99 percent already probably more chance this was a case of semantic variant PPA this is very the strongest one one to one so as the newer pathologist I almost don't need to know what was the story this patient to guess that this was semantic variant because that's what this figure will eventually be associated with in terms of clinical presentation and then there is a very rare type D which is associated with the genetic condition also fed the bones and the muscle is much rare we don't have any case actually in our brain bank here at San Francisco finally the last group the first openness these are the the the one that I write the last it's less than 5% of cases of ft LD some of these forms are genetics and when their genetics they also cause motor neuron so ALS sentence motor neuron degeneration some cases are sporadic instead the presentations that are behavioral variant FTD but usually with the very early age at onset okay so I'm gonna talk now briefly about this last two points of my talk so one is again did neuro degeneration of aging so this very latest finding and late is actually the name that that received and what is the meaning for dementia in the elderly and then the chronic traumatic encephalopathy so remember we talked about this tdp-43 the fifty-five percent of all cases of FD LD right up front to temporal about the generation well it turned out that after we found this protein and we learn how to stain how to look for that in brain tissue did it before it is actually a lot more common and can be seen even in cases type not frontotemporal lobar degeneration i can have any other disease like al sama for instance or Lewy body disease or even not even any of those this is why we call this disorder limbic predominant age-related tdp-43 encephalopathy or late again this paper was published just on April 30th so when this happened basically there is the positional tdp-43 in structure little limbic in the limbic structures of the brain essentially in the pock AMPAS in the cingulate gyrus in amygdala so in structure that are also heavily affected in enough Siemer disease and we found it up in the 25% of cases in autopsy series so these are the regions again of the brain that are affected by this relatively new condition again we known about this now for a while but we now put it together only recently so again the poe campus the temporal lobe of the brain so structures of the brain that are usually very affected and early affected in Alzheimer's disease you can see that the from from this graph that the prevalence of this condition of late in the brain is just increased with age so it's about 10% less than 75 years old but he get much more prevalent up to 70% in individuals that are very old why is this important because we believe it could be the only cause of dementia in individuals who actually do not have a sign but really look a lot like they do have it that's one thing this is the case for instance of a 86 is all man who had progressive problems with memory amnestic dementia but edie biomarkers negative for amyloid and also for tau so she doesn't ever see my disease though she looks like she has this new condition late that really cause a similar type of presentation and it's almost important for patient who do have our summer disease all other conditions because for instance in the presence of late on top of Alzheimer disease they actually undergo a much more severe the generation of the brains a much more severe atrophy of the pocum's which can translate for instance into a faster progression of the disease of faster decline the cognitive performance so this raised one the final question of today talks so is dementia caused by one or multiple diseases of the brain and the answer is that this is actually is probably caused by the co-presence the coexistence of multiple diseases so this is a study done in you know community dwelling cores of patients in Brazil and led by Larry Bird with a collaborator here at UCSF that shows that as you can see it's very common that you can find not just a single disease but eventually two or three or four or even more in the presence of more conditions in the same brain of a person with dementia tends to increase the number tends to increase with the increase in age so a similar concept were actually presented also by another group that Virginia Lee agent Raja now skeena in another paper or just a few months ago so to give you just an example so this is for instance Alzheimer disease cases so you see all cases without summary this is a hundred percent of them of tau deposition and also beta amyloid but I see that 41 percent to 55 percent the cases also do have alpha synuclein 33 to 40 percent of cases also will have a TDP 43 pathology and the same is true for each and every one of the other categories of diseases that we chart today so for instance in Huaraz here hundred percent of them F tau but tends to have alpha-synuclein and the proportion that varies 7 to 22% and also tends to have late 24% for instance in CBD or 16% in PSP the same in tdp-43 pathology the same in alpha-synuclein pathology so while there may be a main a predominant disease that drives the clinical presentation there are actually more than one disease in the brain that is occurring at the same time this is something that we need to keep in mind when we treat when we treat patients so some patients may respond better than others or maybe in order to prevent dementia we had to treat more than one disease at the same time so this table for reason tell us in a study done at Rush University on a research participant who later developed cognitive impairment and underwent autopsy and estimate the what was causing the dementia what was contributing to the dementia so according to this study to this report only 40% of the cognitive symptoms were attributable to Alzheimer disease but the remaining 25% were attributed to the vascular changes so these are important to know because these are things that we can change at this moment we almost have nothing to prevent neurodegenerative diseases perhaps with the exception of physical exercise and social engagement but we do have a lot to protect ourselves from this 24% if we keep up our pressure below certain limit if we avoid diabetes hyperlipidemia if we do exercise a lot if we don't smoke late it plays a very important role that is almost up to 20% it could even be higher than than than what we know and then there's also the alpha-synuclein obody which role is probably half of that fall late finally what supports chronic traumatic encephalopathy so you might have heard about this condition as the condition of the NFL player so this is a disease that seems to be very high in prevalence in people who have been exposed professionally to contact sports and have had a lot of a trauma so repeated repeated concussion it's a disease that's caused by accumulation of tau protein in the brain so but what are the real numbers so a recent study from and make he has shown that this condition is present in almost everyone who has been like an NFL player this regardless of the development of Kannada since a 99% and that the highest risk factor is indeed the presence of multiple repeated head trauma the disease can present essentially in two ways either behave as a behavioral syndrome with increasing irritability explosive aggressive behavior sometimes profound depression often leads to suicide is actually harder disease became actually under investigation an investigation in the NFL court but very often you can also present late in life as a memory disease as a memory problems on a monastic scene oh this is essentially indistinguishable from Alzheimer disease so if a patient come to clinic and as a eastery of a head trauma very often they say is it possible that that trauma is now causing chronic traumatic encephalopathy is it possible that because of that motor vehicle accident that fall that I had reason forty years ago I'm now developing CTE instead of Alzheimer disease even those things look alike well the answer is that if you have a history of contact sport participation and this doesn't matter whether it is professional or not then you have probably a risk of having city in one out of three people who have that history of repeated trauma the counterpart however is that if there is no history of repeated concussion repeated head trauma not only sports but also prisons exposure to blast this is important for our veterans so if there's not that eastery the presence of this condition is almost zero so it almost doesn't exist so it's even in patients who actually do have a history of a significant head trauma so a single significant head trauma is a risk is a risk factor for developing a developing dementia later is a risk factor also for Alzheimer disease but it's not directly associated as we know now with chronic traumatic encephalopathy for that you need multiple hundreds thousands of repeated events that occur like for many years so I'm finally to the to the last slide so how thermite disease isn't it the most common forms of cause of dementia throughout the lifespan but it's not the only one frontal temporal dementia are as common as 18 people who are 65 and more common than 18 people who are younger than 60 so there needs to be recognized they also affect people at the time in their life when they still may be very active and so there is a much larger set of implications in older adults the bench is very unlikely to be caused by a single neural pathological process the rule is actually is that very often we find more than one diseases and the number of diseases increase is holder the patient the patient get so the likelihood developing cinema is really linked to that number and finally chronic traumatic encephalopathy is a new condition but this is very important for people who are exposed to repetitive trauma especially contact sports again and blast but it's unlikely to represent like a serious threat for people who have been exposed to single head trauma in life all right thank you so much for your attention great well thank you so much that was amazing I think you've had the most comprehensive overview of the neurodegenerative diseases so far counting the whole three lectures I think this finalizes the more scientifically based sessions the next sessions will be around prevention strategies treatment and then the final lecture on giving you a bigger picture view of the impact of these diseases not only in San Francisco and the Bay Area but throughout the world we have time for a few questions yes yeah this is a great question and so in this very long lecture but I was asked to talk about everything else so was supposed to hand actually talking about prions so prion diseases are relatively rare condition compared to this ones that we discussed but they do exist and so in the cause basically by these proteins similar to the one that we talk here they have this ability to self-replicate so imagine that there is a product is normal in the brain all of a sudden it changed shape you acquire the new shape that is pathologic meaning it will cause neuronal loss but not only that you start forcing all the other protein similar to do this very same thing so you cannot cop this mechanism that eventually spread so this is how prion diseases were were discovered and again they are rare however we found out recently in the recent years that this proteins associated with Alzheimer disease but also with from the temporal lobe of the generation and Lewy body disease do behave similarly to prion diseases and this is the most interesting features that basically has been proved in this recent paper so this happened to be the case for both beta amyloid and in tau there is a lot of interest because the propensity of this protein to actually cause problems seems to be stronger when we tested the tissue samples obtained from younger patients as opposed to that for patients that develop their symptoms later on so there's a lot to learn about what this really this doesn't mean that this disease is at this moment seen as contagious buddy-buddy basically teach us some basic mechanism that can explain why some people live very very long so by very long with these conditions in other scenes that have a very fast type of progression which is similar to what we see in them prion diseases so so they do but we have to distinguish here the TBI from the from the city that's just because we talked about city tonight so in climatic encephalopathy Tao deposits alone are sufficient to cause the disease and this patient with CTE who don't have any amyloid at all zero in traumatic brain injuries of recent C's for patient has a significant trauma from a motor vehicle accident for instance of other sorts of cause a trigger then there is actually a transient accumulation of beta amyloid mostly in the white matter so in in the long track that is more indicative of the trauma itself but it does not lead to the as thesis files we know to the classic development of Alzheimer's disease having say that though having a history of a head trauma increase the risk for neurodegenerative diseases later in life but not for city but the all the old group of diseases I want to make a comment that I think it's important from your talk that you illustrate it very nicely I hope everybody appreciates that you know this process that we clinicians go through when we're trying to when we're seeing patients trying to you know bring up conger in our minds signs and symptoms clinical syndromes and then try to bring it down to the underlying pathology as you can see it's very complex and as I as I mentioned earlier this is why for us clinicians it's always a better idea to see patients early than late in their disease and because we can more clearly understand what is happening where in the brain is happening and as dr. subpoena alluded to a moment ago this is gonna be important in the future because the the disease modifying therapies that we're all working on will be targeting those underlying proteins I mean that's the model that we're working on right now you hear more about that in a subsequent lecture so very important to think of early early detection yes yeah I think that's a great question and yes it is extremely important so most of the knowledge that we have about this diseases we have the tanks to the generous donation of patients of research participant ultimates really generous gesture to us that are donating their brain and it's there where we find the the response and so the answers for what basically caused the disease and also how we learn really the mechanism of the generation a lot of this discipline of this development in science have really been driven by neuropathology so for instance all those cases frontotemporal dementia did not stained fatale had to be something else and it wasn't until we found it before III that then we learn instead that not this type of generation is actually more common one thing second thing for instance is linked to ALS this is cause joining forces so behavioral neurologist treating dementia in neuromuscular disease has but very often didn't talk for quite some times then we realize wait a minute we are treating the same disease just looking at a different a different aspect so there is there's a lot of initiative internationally and in nation why the National cymet disease Coordination Center the Knox Center is the central repository for for neuropathology for all the new rocket ology data the majority of Alzheimer disease Research Center including ours are involved in a collection of brain samples and many of them not all of them have a neurodegenerative this is brain Bank like the one that we have so the teacher is available for investigators to study just upon request all we need to know is that they're going to make a good use of [Music] that's a great question not at our center but I'm sure somebody's thinking of it I mean more broadly for medicine in general that's a hot topic for sure how do you use AI to better diagnose to be more precise about diagnosis interpreting data but not in our center I don't think anyone is opening up purposes we're not there yet but that's probably gonna be the future but in terms of research there is a lot of interest toward that so there's several collaborators in in our group of the memory imaging centers are actually trying to do this so in using different type of approaches sometimes are completely a purist ik and bias approach mean you know you present a computer like a 10,000 scans and you ask them to classify them accordingly to disease the machine surprisingly that's a very good job but of course I mean very often it will tell us just one disease for instance so you will not have those nuances of looking at okay what else is beyond the first the first disease that is causing the symptoms so yeah I think those approaches will become a lot more popular in the future and very very soon they will translate also into clinical practice I think however you know how our visit with patients are usually very long so a new patient visit sometimes berries for understand two hours to a lot more because it takes a lot to elicit those those symptoms sometimes you can have a conversation that lasts like an hour and a half until you run into an asparagus in a patient who say what is an asparagus so it requires a lot of patience and I don't think that we will ever have a world that would be like clinician free or free from from the direct contact really most of the diagnoses are are done by by the patient the way he presents interact with us and a lot a lot by their families and their caregivers pick each and every one of these no answers we just need to remember and at the time basically to check all the marks so that's that's why the distance to be very long [Music] you

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Keywords: Alzheimer’s, dementia, health, neuroscience, cognition, memory

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Length: 88min 2sec (5282 seconds)

Published: Mon Aug 05 2019