Neurodegenerative Diseases of the Brain

[Music] good evening everybody my name is Sergio lanata I'm a neurologist here at UCSF specifically at the memory and Ageing Center and this is the first lecture of a series that we're gonna have delving on the broad topic of neurodegenerative diseases focusing on Alzheimer's disease but also touching on other forms of neurodegenerative disease this lecture should be an overview of the topic I'm gonna provide you sort of a bird's-eye view of this field and hopefully set the framework for the lectures that will come that are more specific to Alzheimer's disease and and other important topics within the field of neurodegenerative diseases okay so I'm just gonna go ahead and start I think today we're gonna address basically three questions you know what are the neurodegenerative diseases of the brain what do they have in common these diseases and in what ways would they and what key way so they differ again bird's-eye-view okay and towards the end we're gonna have ample time for discussion and questions I'm gonna have two guests that are gonna come over and hopefully we'll be able to ask answer all of the questions you may have so the way I like to start to answer these questions I think it's very important for everyone to have a clear understanding of how doctors think of diseases in general diseases that affect any part of the body whenever we have a disease that affects any organ of the body it's going to produce a series of signs and symptoms of that disease right and there's a difference between signs and symptoms a sign is an objective manifestation of the disease whereas a symptom is a subjective manifestation of that disease and that is objective and subjective to the physician or to the clinician or to the healthcare provider okay and I'll show you an example that is going to illustrate this another key concept is that when you have a disease that is affecting the body in a particular way is going to produce a constellation of signs and symptoms that are characteristic of that disease process okay and we doctors nurses or health care providers call that a clinical syndrome when we see this happen repeatedly right if you have a disease of the liver it's gonna produce a similar constellation of signs and symptoms and we give that a name it's called a clinical syndrome broadly speaking and then sometimes clinical syndromes have their own specific names okay so before we jump into the brain because we follow this logic when we think of the brain I'm gonna show you an example that is gonna feel more familiar to you let's see what happens when you get an infection of the lung okay here I'm showing you a cartoon here have the trachea as going into the right lung the left lung and and some of you may have seen these either cartoons of the lungs it's sort of like a root system you're taking air in and then the trachea subdivides and subdivides into very tiny little branches until the very tips of these branches you have an alveolar alveoli or an alveolar space and this is basically where the air is coming in and is getting shunted into the bloodstream and from there it goes to the heart and from the heart the oxygenated blood goes everywhere in the body so that every organ in our body gets the oxygen it needs when you have an infection of the lung what happens is that the airway and and specifically the alveolar spaces get full of junk bacterial junk viral junk depending on the infection process that you have and this disease process okay in the lung is gonna produce a series of signs and symptoms that is fairly well recognized ever any physician can recognize him so I told you that symptoms are subjective to the physician meaning these are things that I cannot measure I have to trust my patient right so if you tell me they have body aches I can't really measure that I just have to trust that that's what's going on if you have a feeling of low energy I cannot measure that either and so forth right shortness of breath if it's mild and you have this subjective feeling that you know I'm having a hard time breathing but I can see you take deep breaths I have to trust that and chills as well as their mild contrast these symptoms with signs of this lung infection where you would have say a fever I can measure you your fever with a thermometer that's objective right or a cough I can hear your cough or wheezing I can put my stethoscope on your back and listen to your lungs make this noise it makes when they're full of that junk I showed you a moment ago so I told you right collection of signs and symptoms we call that a clinical syndrome and you've all heard what this clinical syndrome is called it's called the pneumonia so the term pneumonia is summarizing this constellation of signs and symptoms that tend to happen over and over again in a person that has this lung disease this long process that we call a lung infection so the concept here is that you're going from a disease process that in this case is affecting the lungs to a clinical syndrome being caused by that disease process by that physical change affecting the organ in this case so that's an important framework to keep in mind because physicians you know use this mode of thinking when they're dealing with any type of disease that is affecting the body so let's switch over to the brain this is a real picture of a brain but when we think of the brain there are some key concepts that make it a bit more challenging to think of disease processes and clinical syndromes and the crux of this is that whereas when you think of the lung in general if you think of any region of the lung top of the lung right lung left lung bottom of the lung the lungs do the same thing they take air in you know they have the same physiologic process throughout right that makes sense but the brain is not like that the brain is sub specialized we call that subspecialization different regions of the brain which in turn correlate with different neural networks connections between neurons to different things in sort of bringing about our human condition let's say and that's a key key concept that I think is very very relevant for neurodegenerative diseases as I'm gonna show you in a moment and that's a concept that we call cerebral localization basically when we neurologists train our car when we go through our training and we're trying to learn about the brain that's what we're doing we're trying to paint a map of the brain in our minds in our brains so we can then know where to look in the brain when we're seeing specific signs and symptoms does that make sense so let me take you through a brief a very brief history of what we call cerebral localization which I define as the mostly precise science of predicting which regions a region of the brain is damaged or malfunctioning based on a careful examination of a patient signs and symptoms right so I'm sitting with a patient I'm paying attention taking notes I'm asking the right questions that's gonna paint a picture of what are the signs and symptoms that this patient is having you know I'm already localizing this to the brain the organ more more broadly speaking but I can narrow it down and think of what are the regions of the brain that are more specifically damaged or not working properly so there's a long history basically that led to us having this understanding of the brain that we have now I mean the brain is by far not a black box we understand a lot about the brain how it works what regions of the brain do what and so if we give you a very very sort of concise history of this and and it takes us back to the 1800s back in the 1800s I'm gonna start the story with the phrenologists have any of you heard about phrenology yeah so very interesting idea led by dr. Franz gall I believe he was German and they had this idea that by palpating by feeling your skull and picking up on certain bumps of the skull I could make predictions about your character your personality your strengths and weaknesses as a human being a very interesting concept right and if you zoom into this picture you'll see that for example they attributed memory to a bump in this part of the head they attributed like language to this area so they thought of the brain as or the mind that really has been compartmentalized into different little separated you know functions and that could be predicted by palpating the skull so clearly they were wrong but they turned out to have the right idea the idea that there is a way of localizing functions to certain parts of the brain everything changed in the sort of mid-1800s when this man Phineas Phineas Gage that's what the P stands for his name was Phineas Gage came his case became very known throughout the world basically this man was is an American he was helping build a railway and they had to use explosives right to do this and what they would do is they would using rods like this one they would put explosives in cracks you know in rocks and they would push the explosive with the rod and and and that's how they would like you know be very meticulous about where the explosion should happen well this this man had an accident basically the explosive detonated before he anticipated and the rod travelled and it entered his head as you can see here from the bottom of the head through the jaw and up through the frontal lobes of the brain right the front of his brain what made his case extremely fascinating at the time and and forever thereafter is that he Lee he lived for like 13 years after this injury so the rod was removed and here you have a close-up of it of how he looked and he kept the rod apparently as you can see here and what was very notable about this case was that this man was described by his friends as being very socially appropriate hard worker sort of a gentleman and a very responsible person and after this injury even though he retained many of his cognitive abilities there was a significant change in his personality all right his demeanor his his baseline traits that made him Phineas Gage and therefore his friends would comment and say you know he's no longer gage you know he was very jocular he became socially inappropriate aggressive you would use foul language and public things that he wouldn't have done before now you have to think that this is the 1800s so this was like completely in a way revolutionary know the idea that wow you can harm one part of the brain and produce a very focal change in a person's personality while still retaining many of the cognitive abilities that you need to continue to work and in fact he continued to work so he kind of changed the dynamic around thinking of the the brain and and and then came this gentleman a neurologists extremely talented called Paul Broca he was French and he had the idea that if there were ever a friend of logical science it would be the phrenology of the cortex meaning the outer layer of the brain not the phrenology of bumps on the head right and he based this idea on observations what he did was he was very interested among many other things in studying language disorders so people that for many reasons developed changes in their ability to speak to understand language and what he did is he looked at their brains and he began to localize you know in the brain specific types of language problems and that's what he what he was known for and then in the 1900s came this man also a German broad man who brought us what we now call the brought man maps and his his reasoning was also quite interesting and an genial for the times I think he said well if the brain is truly sub specialized then I can take an unbiased approach and just look at the organ under the microscope and if there are different functions they should correlate with different structures right so structure dictates function was the idea does that make sense yeah so that's what he did and he basically looked at a bunch of brains and started to look at them super tedious right imagine this word he looked microscopically at different regions of the brain looking at the neuronal architecture of those regions and as soon as you saw a difference in in different areas you would mark that as one region and then move on to the next one right that's what he marked all of these regions like region number one region under two and ingredient number three four and so forth and each of these regions that he's outlined here for instance this region number four has its own saito architectonic structure meaning its own microscopic structure that differentiates it from region six and from region three that's the idea and like I said okay let's find out you know through observation if these regions actually do correlate with different functions and it turns out that for many of these regions that turned out to be the case so right now for example currently we call this region the motor strip because the neurons that initiate movement on the opposite side of the body so this is a left motor strip this this the neurons that initiate moving on the right side of my body live here all of them right for all of us and that's why if we have a stroke that affects this part of the brain then we develop sudden weakness of the opposite side of the body and we ask neurologists have all taken care of these type of strokes however he also found that this region was very distinct Saito architectonic Lee and it turns out that functionally this region is almost exclusively dedicated for visual processing so we see with our eyes excuse me we take information in with our eyes that we see with the back of our heads so that's a fact and and that's how and that's why we've neurologists of all taking care of patients that when they have a stroke on the back side of their brain they develop sudden vision loss but they don't have weakness if it's small enough does that make sense so we have this idea that different regions of the brain do different things however this was not the case for every region that he outlined on his map meaning there were some regions where it was kind of not clear like if there's a you know clear-cut functional functional correlation to that site or architectonic Macan and that brought other maps of the brain that are more closer to our current maps and here you see different colors that take over you know regions that Brotman defined around function similar function okay are you following it might make it myself clear up to this point okay so this is closer to a map that we currently neurologists have in our mind as to how the brain works and fast-forward to more modern ideas of their brain then we're thinking now of like networks not so much of regions although regions we think of regions clinically a lot but neuro scientifically we think of networks how different regions of the brain are interconnected neuronal II to bring about these functions and sort of distributed networks so if you look at this cartoon this would be like how people thought of the brain many many many years ago meaning groups of neurons doing their own thing operating individually and this is more of how we think of the brain now sure there are sub specialized regions that do certain things but they're also interconnected and the idea is that you can injure say a region that is not like the hub of that function and it will still cause symptoms within that network or signs does that make sense okay so that's a very very very brief perhaps biased overview of the process of cerebral localization and this would be an example of a map a simplified example of a map that we clinicians have in our minds neurologists have in our minds when we see in patients so for example we know that the frontal lobes the front of the brain they are important for movement as I told you the motor strip lives in the frontal lobe but other more abstract processes of the human condition are dependent on the frontal lobe like reasoning like our personality traits our ability to multitask concentrate even language when we're talking about the left frontal lobe it's very important for a language function and a vast majority of us we have our the networks of the brain that allow us to communicate understand language and express ourselves live in the left side of the brain then we can think of the temporal lobes and this is highlighted here in blue also shares language functions very important for behavior and personality as well is involved in vision in the visual streams because visual has to go from the eyes all the way to the back so it travels partly through the temporal lobes important for our topic extremely important for memory function especially short-term memory ability for that we have to learn new information lives in the temporal lobe and my colleague George Nelson and next week we're gonna is gonna delve into Alzheimer's disease which is a disease that type tends to affect the temporal lobes although no it's not exclusively and so forth I told you about the occipital lobe predominantly elementary visual processing and and other brain regions so we have this map of the brain that we're using when we evaluate patients that come to see us with any type of neurologic disorder first thing that we do is try to localize where in the brain is the problem and once we have a clear sense of where in the brain the problem is then we start to think of what is causing this problem make sense so let's go back to the brain and if we take a deep dive into a normal brain even though I've told you right there's all these networks that are interconnected different functions related to networks if you really really look deep deep enough into the brain it's all gonna look like a mess right if you look too far deeply it's sort of like zooming into a highway and all you see is gravel but you don't see like the network's all of the highways right so if you really zoom in what you're gonna find is neuro I mean glial cells which are these dark dots here you can see these are this is one of the substrates of the brain they're called glial cells you have the blood vessels just like I showed you the lungs has this sort of like branching system of air of the airway that goes into every part of the lung we also have a similar branching system of arteries taking blood from the heart into the brain branching out branching out so that that blood stream can get every part of the brain and give oxygen to every one of our neurons and finally we have neurons which are this larger cells with a nucleus in the center and a nucleoli and when you look at it this way it looks like it's quite disorganized right I mean there's just no no sense to this but as I told you before these structures these substrates do organize into neural networks okay that that matter clinically there's about there's some debate eighty to a hundred billion neurons in the brain a lot of neurons and maybe the same proportion of glial cells some debate maybe some people think there's far more glial cells but more recently there seems to be like a one-to-one correlation now as I was telling you earlier right different diseases of the brain attack different substrates okay any of these subjects but also regions so you can have diseases of the brain that tend to attack neurons in the back of the brain or neurons in the front of the brain so this is I'm introducing another concept here like the idea that not only diseases can attack different parts of the brain but also different substrates right so to give you some examples we have already mentioned that what we call the cerebral vascular diseases which are strokes this is this is when an artery that is taking blood from the heart to the brain either breaks and and basically other blood comes out and and the neurons that need that blood supply you're not getting it or there's a clot right so that's a disease that affects primarily arteries in the brain but we also have other forms of brain diseases like demyelinating diseases you've all heard of multiple sclerosis that's sort of the prototypical demyelinating disease is a disease that primarily affects a component of neurons called myelin which protects neurons although over time it affects other parts of the brain but primarily it's a mining related disease infectious diseases we've all heard of meningitis or encephalitis it's ER when infections bugs get in the brain and they kind of attack anything they attack blood vessels neurons etc and finally and there's many other categories but just to give you a flavor the the primary topic for this series are neurodegenerative diseases these are diseases that primarily attack neurons not exclusively but primarily at attack neurons okay and Alzheimer's disease is the most common neurodegenerative disease worldwide but we have to keep in mind that there's many other forms of neurodegenerative diseases of the brain some of which you may have heard of like Lewy body disease you've all heard of Lewy body disease it was recently in the news because Robin Williams had this disease and it was made very public that he had this disease Parkinson's disease other diseases that you may have not heard of corticobasal degeneration Huntington disease creutzfeldt-jakob disease these are all examples of specific neurodegenerative diseases of the brain okay now what are these having common so I have a picture here of a healthy brain so let's see this brain is looking that way so that brain is looking this way this is the front of the brain this is the back of the brain this brain is looking the opposite direction back of this brain front of this brain I'll keep it broad this is a brain with a neurodegenerative disease but what can you see immediately you see the shrinkage right or there's a reduction of volume right and I would say that in the case of this example the reduction of volume is more pronounced in the front of the brain than in the back right if you compare the back of this brain it looks about the same as the back of the healthy brain do you agree no relatively speaking I couldn't I couldn't size them the same but trust me that the concept is that this is a focal process and that's another important concept that we keep in mind when we think of neurodegenerative diseases the idea that each neurodegenerative disease is attacking a specific region of the brain initially in the initial early stages and therefore it's causing shrinkage or what we call atrophy of those regions right preferentially this is this is a key concept about neurodegenerative diseases that not the the entire brain is not attacked at the same time different regions are attacked at different time times in the disease history and therefore the signs and symptoms and you already know what a sign and symptom is are different for each neurodegenerative disease and we can see this on MRI these are some pictures of the MRI just to orient you a little bit this is the right eye this is the left eye these are pictures taking what we called axial pictures in this way and what you're seeing here compared to a healthy brain below is that there is an enlargement of this salt site basically the enfold in between the brain tissue in that area has widened right because brain tissue has been lost in that region can you all see that compared to the picture in the bottom where it's fuller so basically every part of the brain here that is showing areas of blackness that I'm outlining here with a with the mouse is fluid that has replaced the area where a brain used to be okay versus in the bottom picture you see that it appears that there's more brain tissue than fluid right similarly if you look at this slice which is a little bit higher up sort of like this region you see that the frontal lobes this is the front of the brain have also shrunken and therefore you see more fluid surrounding those lobes right compared to the healthy brain where it appears a little bit fuller do you agree okay and this is a sagittal view this is as if I were to cut the brain this way and you can also see that there is more of that fluid between the brain tissue that you would see in the bottom okay so again this is the concept that different diseases of the brain are gonna produce these focal patterns of atrophy in the early stages of the disease and that's something that they they tend to have in common dr. Seeley who is a member of our memory and Ageing Center has looked at this with modern imaging and what he's found is that different diseases of the brain so I mentioned that list earlier Alzheimer's disease from the temporal lobe or degeneration corticobasal degeneration they tend to affect different networks and I showed you what I mean by a network earlier selectively okay so meaning the idea that in the very early stages of these diseases they will attack different regions of the brain selectively and from there spread onto different regions so look this begs the question right why is this happening why is there that shrinkage what is happening inside of those cells inside of those brain areas so when when a neuropathologist neurologist or a pathologist that is interested in studying the actual disease process of the brain looks inside of these brains they will they will find a few things but I'm showing you here a little menu okay this menu is far more extensive the idea is that different diseases of the brain different neurodegenerative diseases of the brain correlate with different protein inclusions abnormal proteins that start to accumulate in in the patient's brain and over time that progressive accumulation is going to cause damage sort of toxicity to the neurons in those regions so I'm just going to give you a few examples my colleague salvos Pina is going to come back come to I think it's the third or fourth lecture he's going to delve into this more in more detail I just want to give you a little a little overview here so we have for instance what we call tau proteins right that may come in different flavors so the protein itself is the same but depending on the conformation it has a three-dimensional conformation of that protein what it looks like chemically we call it different names okay so for instance we have a neurofibrillary tangles tile this is the protein that we see in Alzheimer's disease as my colleague George Nelson is going to show you in more detail next week we have tau that can come in the form of a pig body this is the type of tau that we see in frontal temporal dementia okay and we have also tau that comes in the form of a toasted tufted astrocyte which is associated with a different neurodegenerative disease do you understand I making myself clear there's a correlation between a specific neurodegenerative disease and a protein inclusion in the brain that a neuropathologist can find can see likewise with a different type of protein d what we call the alpha synuclein protein which whenever adopts a confirm you can see here that neuropathologist would say well this brain I think had Parkinson disease or if it has a different conformation it would be called Lewy body disease okay in the right clinical setting of course yes the question is if we can see these proteins through imaging through MRI yes diagnostically or not not through MRI cause MRIs are just pictures of the brain you know the outside really or cuts through the inside but they don't allow you to see microscopically what's happening inside of neurons or around them but we are developing different imaging modalities especially specifically PET scans for instance as you'll learn next week we have a PET scan that can detect I'm not showing it here but can detect one of the Alzheimer's disease is associated with two proteins in the brain one is tau another one is beta amyloid and we have a PET scan that can catch that bed amyloid in the brain so that's gonna be a topic of discussion next week so that's the idea though the idea is that these these diseases are caused by a real objective sort of physical changes that are happening to the brain which in turn are producing specific signs and symptoms as I explained to you earlier the difference between a sign and a symptom that coalesce into a clinical syndrome so each neurodegenerative disease of the brain is caused or we can more more scientifically say is correlated with a progressive accumulation of specific pathognomonic protein inclusions or protein OPA theis that's the term that we use and over time this accumulation becomes somehow toxic to the brain right and leads to degeneration inflammation and atrophy shrinkage of those brain areas am I making myself clear up to this point okay so you know the way I try to imagine this is if I could put like grains of sand in my in my brain right if I could like take my skull oven and slowly every day put grains of sand one of you know because we have a hundred billion neurons it's not gonna do any damage right but if you do this over many years eventually the brain will have trouble functioning properly that's the idea there is a lot of research and and controversies around this concept I don't want to say that that it's all like perfectly clear because some people say well maybe there's something else happening some researchers that is causing this but that's not really the cause right so there's a lot of research going on in this area so basically if we put this in our cartoon schematic you have different neurodegenerative diseases they have in common they have a sort of a shared neuronal pathology but also different neuropathology depending on the protein inclusion that is affect that is causing it or that is associated with it but they're all causing neuronal death as well as glial proliferation those glial cells I showed you them to proliferate and that's sort of a pathologic summarizing very succinctly that pathology hallmarks of the neurodegenerative diseases and this process is causing a clinical syndrome or a group of clinical syndromes if I jump a little bit to a lecture you're gonna have next week this is how this map would look like for Alzheimer's disease AD so you would see in the brain two proteins that are leading to toxicity of the brain one is the amyloid beta protein the other one is the tau protein or the amyloid plaques or the neurofibrillary tangles they're accumulating in the brain but interestingly depending on how this disease affects the brain meaning what regions and you know now you have a sense of cerebral localization as I showed you earlier depending on what regions of the brain are affected by this by this pathologic process the same disease process is gonna cause very different clinical syndromes okay in the early stages of the disease by far Alzheimer's disease most commonly will cause a characteristic memory syndrome that everybody is familiar with when they think of Alzheimer's disease but there's other syndromes that can happen as a result of Alzheimer's disease which my colleague is gonna explain to you and illustrate to you these maps can get very complicated for in for a neurologist this is a different disease called frontotemporal lobar degeneration that we in our Center are very familiar with unlike Alzheimer's disease which is caused by sort of the same pathologic process those tools proteins that I mentioned in the case of FDLE frontotemporal lobar degeneration you have multiple possibilities of different pathological pathologies that that may be causing the problem as you can see here these each one of these is one type of pathologic process and in turn it causes a myriad of clinical syndromes depending on how these proteins affect the brain okay and and this is going to become clear by the lecture that my colleague solve a salvo spin is gonna give later as well okay so that's sort of a quick overview of the the neurodegenerative diseases that sort of looking at it from the pathologic perspective and touching briefly on the syndromes but you may ask yourself well what about dementia I haven't used the word dementia right I've done that on purpose because the way to think of this is as follows imagine that this is a person that is going through the neurodegenerative disease process okay and we know most of what I'm going to show you from studying Alzheimer's disease but we think it also applies to many many of the other neurodegenerative diseases I've mentioned so this person goes through an initial stage where the person is healthy if I meaning that if I were to take a piece of that brain look at it under the microscope I wouldn't find any evidence of any worries on worrisome degenerative changes okay that's what we define as a healthy brain but when that person gets into the sixth decade approaching the seventh decade he may enter what we call an asymptomatic stage of this of whatever in the road neurodegenerative disease were thinking of me let's say that this is Alzheimer's what does that mean that means that if I were to be able to take a piece of that brain and look at it under the microscope I would already see these proteins and the damage that is being caused but but the person feels fine and the family cannot see anything abnormal that person would come to see us and we wouldn't detect it on clinical examination we wouldn't detect anything wrong with the person does that make sense so as sort of an asymptomatic because you don't have signs and symptoms of the disease but if for any reason I could look inside of that brain I would see changes physical changes already okay then the person enters this phase that were stage that we call mild cognitive impairment caused let's say in this example by Alzheimer's disease what does that mean that means that the person already having signs and symptoms but they're mild mild in the sense that they're not severely interfering with a with a with a person's independent living the person can still go about living independently but as the disease advances and this person enters say the eighth decade and this is very the age ranges are very different for every individual of course then finally that person enters a stage that we neurologists call dementia meaning that there is severe cognitive impairment and by severe we mean that it's really affecting affecting independent living okay so we use the term dementia analogously to the we specialist and we have a memory and Ageing center analogously to the way I showed you earlier we use the term pneumonia it just encapsulates a certain set of conditions right in this case cognitive impairment that is severe enough to interfere with independent living and we can say in this case I'm seeing a patient that has dementia due to underline Alzheimer's disease does that make sense okay so this knowledge has really shaped our approach to studying these diseases and we think of research around primary prevention meaning what can we do to hold ourselves in this stage to keep our brains healthy and not develop the disease right that's called primary prevention and also secondary prevention let's say I have the disease but I'm either in the asymptomatic phase or I'm mildly symptomatic what can I do to stop it drug wise lifestyle wise and one of my colleagues is gonna also talk to us about what we've learned from from taking that approach what are the lifestyle factors that protect our brains that strengthen our brains that may keep our brains healthy or if we have a already and inswing disease and it's mild are there things that we could do that potentially not guarantees but could potentially you know help us fight that progression okay now I have to be frank almost all neurodegenerative diseases of the brain beginning seriously and progressed real and relentlessly over the years this is a fact for practically all of the neurodegenerative diseases they do not get better they progress they get worse through the years sometimes there is a plateau you know where for a few years maybe it seems like not a lot is changing but over time big-picture view is that things do progress and they progress to the point of leading to disability and death meaning that we do not have drugs that can cure these diseases and we are of course us in the memory and Ageing Center and throughout the country working very hard to find cures to find drugs that can help us prevent these diseases or stop them and I think as you'll hear later by my colleague Julio Rochas he will tell you all of the efforts that we've been doing to try to develop these drugs and we think we think we're close but we're not there yet quite quite yet another thing that these diseases have in common is that they they have a very very strong impact in society I took these figures from the Alzheimer's Association so they pertain mostly to Alzheimer's but we can think of them more globally as pertaining to neurodegenerative diseases and more more broadly so Alzheimer's disease six leading cause of death in the United States 16 million Americans provide unpaid care for people with Alzheimer's or other forms or other causes of dementia so imagine the societal costs of this the economic cost estimated that caregivers provide eighty eighteen point four billion hours of care that I'm asked to two hundred and thirty two billion dollars so very expensive disease as a group of diseases they have a very very hard impact on our societies in our economies so this brings up the issue of early and accurate diagnosis meaning let's not wait until a person has dementia right they have severe cognitive impairment that is impeding independent living but let's try to move the the focus on the early stages why so we can better prepare patients families to confront these diseases and plan for you know economical reasons psychological reasons you name it there's many reasons why it is a good idea to try to shift things toward more early stages economies predict that preventing or delaying the onset of Alzheimer's by five years would cut Medicare spending for Alzheimer's by half so there's a big economical push as well because as we live longer and we know that these diseases are one of the biggest risk factors for this disease as a whole is age the longer we age the greater our risk is so we're working hard to try to find something that can prevent them or or hold them off alright to start to finish up what I want to do and this is also important to set the stage for the lectures that come after this one is give you a little glimpse of how we evaluate patients it's another thing that we that these diseases have in common meaning that we take the same approach to the evaluation we clinicians when we suspect there's a neurodegenerative disease we take the same approach in the memory and Ageing center to try to evaluate these patients so guiding the whole process of diagnostic evaluation is this map that I showed you earlier right so we all have this the cerebral localization map that really guides our interview and an examination of our patients we take a very detailed history our history is driven by our knowledge of the brain we know what different rage regions of the brain do so we ask the right questions that pertain to each region this takes a lot of time very important if for around this topic is that for us clinicians it's very very much I don't know it's easier makes our job easier if we see patients early right if you can imagine if I'm seeing a person that is having cognitive impairment or behavioral changes that they've been dealing with it for say eight years it's very hard for us to like peace out all the history so we can make sense of how it began where in the brain it began and and try to understand the disease right we couple the history with a neurological examination where again it's very much driven by the brain localization map that I showed you earlier and this can take anywhere from one to three hours depending on the complexity of the history and sometimes we get different views sometimes family members have one family member has one view and another family member has another view and we have to try to yes question sure so as I was saying earlier we have a region of the brain or it's it's actually shared across different lobes of the brain it's it's mostly in the left of the of our brains the left hemispheres where all of the neurons and neuronal networks that are dedicated to language function live and the way we one way that we try to think of this is you know those regions that are involved in expressive language function I believe to to express ourselves and regions are involved in receptive language function it's a very simplified way of thinking of it but yes understanding what people say comprehending the content of language it's not about so much at once once the a message has come in clearly has to go into the brain and has to be process sort of like vision that I showed you earlier they you know nothing happens in the eyes all of the processing happens in the back of the brain most of the processing then we couple that neurological evaluation with what we call a neuropsychological evaluation and these are basically paper and pen examination tests that are ideally performed by a neuropsychologist where the patient comes in they do a bunch of test testing at different regions of the brain again it's very much you know guided by the cerebral localization testing different regions testing memory function executive abilities language function and obtaining sort of a more objective sense of how the brain is working the advantage of this type of testing is that we can compare those results to results of other normal people that have the same age and education as the subject we're testing so we have a sense of where that subject stands compared to a bigger population right and and we're we're basically correlating the neuropsych testing with our examination and in history and then we couple all of this with investigations we do imaging we may do bloodwork we may do other forms of imaging that you're gonna hear more about next week we may do cerebrospinal fluid analysis it's a lumbar puncture and again you'll hear more about the utility of Serio spinal fluid analysis next week as well because you know as I showed you earlier or maybe maybe this wasn't so clear when we see a person that has cognitive impairment meaning even cognitive impairment that is severe to a point of you know causing disability that doesn't necessarily mean that the person has Alzheimer's disease or that the person has a neurodegenerative disease it may be something else causing that impairment right it may be even certain vitamin deficiencies like b12 deficiency and can cause a lot of confusion and cognitive impairment that may look like Alzheimer's disease okay so that brings up the importance of you know like saying that someone just has dementia right when you take your loved one to a doctor and the doctor says oh I think he has dementia that's not enough we have to find out why the person has dementia right so basically you combine the neurological evaluation neuropsychological testing investigations key is the level of Independence how independent that person is and all of that together gives you a clinical diagnosis that then you use to come up with a plan a treatment plan a support plan for the family and the patient okay so neurodegenerative just some key points you know neurodegenerative diseases differentiate themselves according to their microscopic or histologic characteristics and their tendency to selectively affect different regions or neural networks of the brain I think I've showed you that another key concept is that depending on that regional involvement of different diseases in the early stages is what dictates the different clinical syndromes that you're gonna learn about more in subsequent lectures and that's the concept of cerebral localization that I showed you earlier in general with a few exceptions neurodegenerative diseases advanced very slowly and they go through these stages we think where a person maybe even an asymptomatic phase for years before they become mildly symptomatic and before they enter a more later dementia stage of the illness although we don't have drugs that can hear or stop these diseases we do have a lot of drugs that can help symptoms that can support patients and families we have a lot of you know management strategies and and more recently preventive strategies to that we and you'll learn more about those as well later and as I also mentioned the the accurate diagnosis and by accurate I mean when a person comes to my clinic after say eight years of disease and then the family wants to know what is causing this that can be a little bit challenging because it's been such a long course and I'm seeing the person late in the disease so just something to keep in mind I think for for for you guys and as I mentioned there's many reasons I haven't mentioned all the reasons why early diagnosis is important and and we're going to talk about a little bit more about that later as well so I think that's all I have thanks for your attention now I have two amazing guests today I have dr. Bruce Miller he is the director of our founder and director of our of our memory and aging Center basically dedicated his whole life to this field [Applause] and we also have Mary dr. Mary Lou or not MP nee she she has also dedicated part of her life to the to a study a big part of her life to the study of these are degenerative diseases in her area of focus has been on studying the neurodegenerative diseases that affect language function so that's mostly been her focus so we have them as guests and they're gonna help us navigate any questions you have I will start off with a few questions for them and then we can get the audience going so my first question is to dr. Miller so maybe you can provide us with a sort of a historical view of things because you you've been in this field for a long time and I would put you next to Paul Broca maybe later down the road it was never wild so I trained as a fellow in behavioral neurology between 1983 and 85 I was probably the first generation in the 20th century that focused particularly on dementia and at the time the teaching was that all dementia was Alzheimer's disease and and there had been a very strategic reason why that happened and that was a very brilliant man named Bob Katzman in 1975 who was studying Alzheimer's disease realized that there was no funding for Alzheimer's disease to put that in perspective we think for incredibly complicated but good reasons that our budget at the National Institute of Aging in 2020 will be three billion dollars so around that time it was maybe a hundred thousand dollars and and he looked at a number of studies that showed if you were in a nursing home and you died with a cognitive disorder that was very likely that you showed plaques that Sergio talked about in tangles and so people correlated one to one Alzheimer's disease with dementia and I think it had a lot of really good things that happened the NIH started to put money into funding this clinic started to think about it but I think the next big wave of findings was the realization that very specific genes and they've been knocked off one by one the first was discovery that the amyloid protein gene could if mutated could cause Alzheimer's and a little bit later it was discovered that another gene called precent Ellen would cause Alzheimer's and a little later it was learned that there's a gene that many of us carry a pony for that increased the likelihood of us getting Alzheimer's disease so that was in the 90s and they were all Alzheimer genes but then around 1998 genes associated with a different dementia frontotemporal dementia were discovered soon after that genes that cause Parkinson's disease were discovered and I think simultaneously we in the field we started to realize that we needed clinically if we were gonna make any progress to differentiate Alzheimer's disease from frontotemporal dementia from Parkinson's disease with cognitive impairment and and so slowly we have evolved you know I think in a very sophisticated way our diagnostic capabilities in fact they have far outstripped our treatment capabilities so we are now incredibly precise don't don't believe that you can't diagnose south-south all may tell you this in a week or two but don't believe him that you can't diagnose Alzheimer's disease without a pathologist we're in credit we accurate had seen those proteins in the brain now and when we're living and we may be perfectly asymptomatic so I think our diagnostic ability is now precise for most of these conditions we can start to see changes decades before someone gets sick and I think you will hear about this new wave of therapies that are focused intensely on early interventions and I think the next decade will be the decade where degenerative diseases start to have really powerful therapies so that's one stream and then just one other quick one which is a lot the three of us worked very closely in our global brain Health Institute and that is very focused on this other side which I think many of you must be interested in which is we know that if you live a certain lifestyle if you're lucky enough to be born in a family where you get a good education where nutrition is good where you see physicians who treat your hypertension you are 1/3 less likely to get Alzheimer's disease so I think we've learned that how we live our lives and if again some of this is luck just where we're born but a lot the way we use our brain in life the way we are stimulated in our daily activities whether or not we exercise my Pilates teacher is here everyone must do Pilates at least once a week so these are you know some of the things that we're learning great and I also have a question for dr. Gordon beanie because one of the in my opinion one of the fascinating things about this field too is that we learned so much about the human condition really by studying the neurodegenerative diseases I mean and and like the whole concept of localization and we can tell us a little bit about your trajectory and how more recently you've become interested in you know studying dyslexia based on your experience studying the language disorders caused by neurodegenerative disease sure so as a surger was saying I'm particularly interested in language in the brain so the networks in the brain that have to do with language which is a very unique human function of all the ones that we've talked about is basically the only one that is really specific to humans especially written language how written language developed so we don't have a language written language gene the brain hasn't had time to evolve to develop specific circuits for reading and writing is a it's a relatively new function for us it's 5,000 years old so we don't we don't it's not enough for evolution to create a new brain circuit so in some ways and is an incredible example of brain plasticity how do we take the areas of the brain that we use for speaking and seeing and we turn them into a machine that is so efficient at reading and writing and and is a very specific machinery that has specific anatomy and physiology in the brain and what we started seeing in our clinic for adult patients and aging patients with this specific near the genitive diseases is that in certain people those are the networks that are attacked by these diseases so and these individuals Alzheimer's disease instead of causing a problem with memory it causes a problem with for instance speaking or reading or writing or remembering words and memory of everyday events is totally fine and this is very puzzling why the same disorder the same proteins that Sergio was talking about amyloid and tau in certain people hit the areas of the brain that are involved in memory and in others the ones that are involved in reading and writing and and we still studying this it was a big focus of our research but what we started noticing is that when we started asking and listening to those stories that patients tell us that take so long and that we love so much they tell us so much about the person is that certain the majority of these individuals told us that they had trouble actually learning to read and write when there were children and actually there were in readers all their life they did find I had a lot of strengths and in other cognitive areas but their brain somehow was always kind of a symmetric so that language network that later on was affected by these disorders might have developed differently to to start with and that actually our brain health is a it's a lifelong journey that we need to look at it's not that when someone becomes 18 years old then we don't ask them anymore how their brain functions developed to start with and so that there might be some susceptibility of specific brain types and specific ways in which the brain develops that predisposes or protect us from developing some symptoms on that pre-symptomatic face that Sergio was talking about we also call this cognitive reserve so there might be some individuals that have a longer a symptomatic face because they've used their brain enough they've had higher education they've learned kept learning new things kept exercising their brain and so that area that period of time in which maybe the disorder has started but the symptoms don't occurred might be longer so in that sense someone who has a developmental disorder like dyslexia might have a weakness in the language system but we can also say they're protected and their memory and visual spatial functions so they only develop a problem with language and they don't develop a generalized dementia until much later so we've in trying to pursue this line of research we started seeing children and family with neurodevelopmental differences and and to try to understand this lifespan approach amazing yes the question is what about genetics oh absolutely so there are certain forms of the of these disorders especially that start very early let's talk about Alzheimer's disease there are forms of Alzheimer's disease that are genetic and they're very clearly inherited there is one gene that we call dominant and if a person have it their children have 50% possibility of having it they're very rare and they usually start very early in their 30s different genetic diseases have different links to different genetic genetic mutations or genetic predispositions because they're really different diseases from a molecular point of view so for instance frontotemporal dementia that we study in our Center is more frequently genetic than Alzheimer's disease and can be caused by different mutations but as dr. Miller was saying Oh neither you or I should say a word about polygenic risk that's right so so yeah I mean Marla was talking about these unusual genes but gosh we see a lot of people who worry my father got frontotemporal dementia in his fifties you know that's very young do I carry a gene that causes from the temporal dementia so we we think a lot of that about that with people but the more common genetics and and my friend Giovanni Coppola at UCLA who was a really superb geneticist thinks about 65 to 70 percent of Alzheimer's disease has a genetic component but it's much more complicated than a single gene and so what one of the the most brilliant people I ever met is a radiologist named Raul desiccant who is beloved to us he has developed ALS but with the condition he has just done this pioneering research on polygenic risk scores and and we think in the next decade when you come to see your doctor whether it's as a child or as an older person the the physician or genetic counselor will be able to say to you well your polygenic risk score for this set of diseases is fairly high these are some of the genes that we think you can do something about by lifestyle by vitamins by other other interventions so most of us if we get Alzheimer's disease there are two big factors one is age and it's a myth that this disease stops once we hit 90 it continues to go up so you know if you're a centenarian you're pretty unusual if you have cognitive normalcy so age and there are a lot of reasons for that and maybe salvo will talk a little bit about that but the other is having genes that increase or decrease our susceptibility to different diseases and also whether it's Alzheimer's ALS you name it a question here in the front the question is if we've ever had experience with an electro acupuncture for treatment of Alzheimer's I don't think we have we one of the lectures in the series will delve on alternative therapies what value they have so we're going to delve into that topic a bit more so I've been asked to repeat the question so I'm going to repeat that question the question is so what we're trying to say is that maybe my grandmother's Alzheimer's neuro pathologically was not really Alzheimer's it was something else and the answer is a resounding yes I mean it's it's every time I hear I'm taking a medical history and any of us are taking a medical history we hear oh yeah my grandmother had Alzheimer's the next question is what tell me about her symptoms like do you know what she had tell me the story so that opens up a whole discussion about what were those symptoms and for example if we start to hear and dr. Miller can talk more about this too like we start to hear a story of you know early behavior changes that led later to dementia then we think well maybe it wasn't Alzheimer's maybe was frontotemporal lobar degeneration I don't know if you want to add the first symptoms were visual hallucinations it's often part of a Parkinson's just the other thing I would add is I think we have 30 Alzheimer centers across the United States that study people longitudinally from the time they're healthy into a diseased state and if they'd want us to study their brains after they pass we do and one of the big findings I think this is relatively new as we think once you reach the age of 80 you may well have more than one protein responsible for your degenerative disease so it's it's it's not rare to see someone over the age of 80 who has Alzheimer changes that are significant but also some changes in Parkinson circuitry so they have Lewy bodies alpha-synuclein they may even have some frontotemporal dementia proteins plus some vascular disease so I mean just my belief is that we've oversimplified this process and I think it's led to catastrophic results in drug trials I mean for me one of the most catastrophic billion-dollar failures was thinking that we could lower amyloid in the brain of 90 year olds or 95 year olds and expect that we would have a dramatic cure for these conditions when in fact some of them didn't have amyloid in the brain even so you know I think your your questions a real really good one and I think we're gonna go in a very different direction specific we know exactly the cause then treatments may really work so the question is are there like specific signs and symptoms that mean okay you have to get checked we're gonna delve a little bit more into that in the next lectures when we start when we get more in-depth into Alzheimer's disease but I I think I can save and and you you can comment as well of course but there is no single sign or symptom that means you have to get checked I think the way I see this personally is we all have a sense of who we are you know our our core traits and strengths and weaknesses cognitively like we heard before like the concept of cognitive reserve and what are our strengths when we feel that any of these aspects is has is being attacked by you know you feel like it's not just a senior moment or like the occasional oh I forgot my keys but something that you're seeing happening daily and over the course of months to years is getting worse and other people who are noticing it that is clearly a reason to you say you know I should be checked because I as I said earlier not every person that has cognitive impairment has Alzheimer's disease or a neurodegenerative disease there may be something else going on yes and that's what I was gonna say don't hesitate if in doubt get jack do we get our you know routine blood work and our routine blood pressure checked and we should get a rain check routinely as well and we'll have soon more and more effective tools to do that digital tools that hopefully we'll make available to primary care physicians so that they can check our brain muscles they say their brain networks very easily at our yearly checkups and then we can have because the best way is to have longitudinally to have many assessments yep so I wouldn't hesitate and don't be scared we're not scared to check our blood pressure we shouldn't be scared to check our brain functioning and and this is a usually a motivating factor for people that participate in healthy aging studies too to come in we have a healthy aging study we start seeing people and even in their 40s that come and check in with us every year every two years and we do a comprehensive evaluation and we collect all this data for research so we can understand Aging next question yeah the question is the relationship between sleep apnea and cognitive impairment more broadly I guess yes sleep apnea is one of the medical conditions that we know is a risk factor for cognitive impairment so whenever we see a patient that is having cognitive issues and has a specific of cognitive we think of obstructive sleep apnoea like is that a diagnosis do we need to work up the patient for obstructive sleep apnea the good thing is that there is a treatment for absolute obstructive CPAP it's not a great one because it involves a mask at night but most people get used to that mask and once they once they get used to it and they can see the benefits the following day then they just don't want want to go anywhere without it I mean that's my experience next question yes sir maybe dr. Miller can address this question and repeat at Dena Dena Duval's research at rofo protein yeah so about six years ago Lenart mookie with Deena Duvall studied in in in mice and humans and in the human gene Yokoyama was the scientists who worked on this a gene that we carry Clotho and their different forms of Clotho and if you carry the right form of Clotho you live longer not only that but you seem to have a slightly bigger right prefrontal cortex I would love to have that I probably don't have the right gene for that one but um with with that said I think there's a lot of hope that this might be druggable so that we could get the right level of Clotho in our blood to get that boost in aging that is associated with it and so that this is very much the area that Deena has worked on since she left working with Leonard and I think it's a very interesting area and it it would be part of our polygenic hazard score so if you have the right combination it would lower your susceptibility to getting Alzheimer's disease probably so that this is just one of the thousands of genes that smart people are thinking about so now in our research we get the whole genome on everyone every single person in our healthy aging in Mari lose language cohort and Sergio's a cohort of homeless population in this city and people in the mission so we are just getting huge amounts of data and and think you know slowly but methodically about what which ones of those genes might be protecting us which ones might be a target for specific therapies question here the question is environmental factors and if there's a link between them and different diseases anyway what do you want to take a stab well I mean I think Sir Joe we're all thinking a lot about this so in our global brain health program which is focused on underserved populations who have greater risk for these you know environmental pollutants some this is a big deal in California Carly Tanner has shown that our migrant workers have much higher not not a little bit but a big higher prevalence of Parkinson's disease almost certainly pesticide induced one of our fellows next year is coming from University of California Fresno - and she works with the farmworkers to try to clean up the environment for the workers in the fields but of course it's relevant to everybody in California if you're eating food with pesticides you know this can't be a good thing TUC Finch recently at USC did a really elegant study looked at people who live to right against the the Harbor Freeway the 110 and showed that if you lived right adjacent to it you had higher rates of pollutants in the air and higher rates of Alzheimer's disease so we've just come back from Brazil which is a beautiful country gorgeous country with massive pollution issues and this will only compound the other risk factors like low education and certain populations lack of universal health for people's this is really an important area I was I just wanted to say that apart from chemicals environment you know we need to think of the brain is really plastic and so the environment in terms of trauma and lack of education and psychiatric disorders depression are also very important in protecting the brain and delaying in neurodegenerative disorders so that's what's something that surgery and I are very passionate about I have a study in prison and surgery in homeless populations and it is really striking to see the effect on the brain of these incredibly stressful living situations and they would certainly be a risk for brain health in the aging stage of life as well sure so you know as we've already mentioned we I am interested in studying what we call the most upstream factors that may be contributing to neurodegenerative diseases right so we tend to think of you know if we first focus on the disease and we start to think of the risk factors like medical conditions behaviors but as we've already mentioned there's a whole bunch of like social conditions what we call the social determinants of health that affect brain health right and so the work that I'm interested in doing is leveraging the amazing projects that we have in the memory and aging Center and collecting this detailed histories is life course histories of people people across all walks of life you know homeless people people have become homeless people that come from different socioeconomic backgrounds different life trajectories and objective izing that information and then correlating that with brain health so so the way that we're doing that is by partnering with different organizations in the city and in the Bay Area community centers that are seeing patients from very diverse walks of life and you know I run a volunteer clinic in in the mission another one in the General Hospital I go there and see patients and we also give talks in the community like this one so we can get people motivated you know people across the city different neighborhoods motivated to come to our Center and once we're there in ER Center we can have these very detailed discussions of their life right and trying to objective eyes that information and then correlate it with brain health that's my hope okay so let's start again in the front here so the question was is that there is some maybe increase ability to diagnose nearly generate diseases Alzheimer's disease but what is the trajectory in treating it and will there be an arc maybe like in HIV and I think there certainly will be and I think the issue was that we weren't diagnosing these diseases properly and at that point when we're not diagnosing it properly and we really don't know what's going on in the brain what is causing these symptoms then we cannot treat it properly so as Bruce was saying if we treat Alzheimer's disease just as an amyloid disease even just how we're not looking at and and maybe within those trials at the beginning we really did not have molecular diagnosis back then so probably there were a lot of patients that didn't even have Alzheimer's disease to start with so correct diagnosis correct differential diagnosis is the starting point to then develop what I think will be multi therapy treatments based on these polygenic risk factors and environmental factors so there will now be just one treatment yeah I like your question I'm not quite as pessimistic let me pray so I think we where we are with treatment so it's disappointing I know and and I think there's been you know know really new compounds since 1997 when a compound called donepezil or aricept was a FDA approved there's another one but it doesn't work nearly as well as aricept and so the average person who takes if they really have Alzheimer's or if they have a Parkinson type degenerative disease I like to say in my clinic I my hope is and on average the person who takes this is about where they were after nine months so it's not a cure but it is somewhat improving where people are for I think a significant period of time then all sorts of unbelievable surprises from people like Mary Lou so let me just give you one example I'm her I would never have thought that the progressive aphasias are progressive right they're degenerative they're bad proteins could have a behavioral intervention but Mary Lou and her group a woman named Maya Henry from Texas have shown that the different types of aphasia if you give a smart intervention can really be slowed down and let me give you one example of something that was very touching to me so I have a patient I was very close with who had a progressive language disorder and I talked with him in June and he said my daughter is getting married in September he could barely get that sentence up and he says I want to give a speech at her wedding in September and I just thought no not impossible so Mary Lou's team started working with this gentleman worked on the script practice it over and over again and he gave the most eloquent speech at the wedding everyone was in tears he came back you know to our clinic you know he was like a hero to us and and and the data I mean the data is really good it's really good for speech interventions it's not a cure but it does something really good on exercise I think data is not terrible around diet either so III do think we have interventions the big powerful cures biological cures I do think will come and I think we work with the best biologists in the world at UCSF I think that's our responsibility and mission and so we're working with the discoverers of CRISPR to think about whether for certain genetic forms we could edit out the bad gene we think that will happen five years eight years so I think really great therapies are just around the horizon but doing nothing or not you know intervening is the worst thing that can happen so different symptoms are different in different brain networks and more trainable than others it's not they hold on for a while and then hold on for longer if you practice longer in the right way as as verse was saying they're not cure but giving another year of speech to someone whose speech is declining really fast is still very significant and there's been this kind of attitude of there is nothing to do for instance speech pathology was not even covered for these patients and and is really not fair because even you know it's covered only for patients who had a stroke and lose language and not all of them recover they get a little better but they might not recover but it's still covered by insurance and for our patients who sometimes are very young in the 50s and 60s it was not even covered because there was kind of this pessimistic idea there is nothing to do and it's not true there is a lot to do so I didn't mean to be pessimistic at all thank you very on how much we can do on the molecular cure we're not quite there yet but of course we need to do interventions even cognitive intervention really based on the most accurate diagnosis of which networks and which symptoms are affected and is the same that we see with children with developmental disorders there is not one dislikes the other is a lot of developmental different developmental strengths and weaknesses that we need to really diagnose exactly to give the right intervention that is effective so that the question is if we could comment on the work of the old Britain it's a package of things that are well known and I believe in like exercise Mediterranean diet prevention of cardiovascular risk factors so standard care I think a lot of vitamins which my guesses do more harm than good but nobody's going to study at including Dale so we'll never know it's expensive if you're a fireman you could spend your whole pension on it we let me go to the next row and then we'll come back yes sir and the lay news about possible cure for Parkinson's disease British and I wondered what the what it was that they found and I'm also curious what's the relationship between let me say something about cures so I'm you know I started studying Alzheimer's as a fellow in 1983 and I would say every six weeks there's been something in the news and God bless my patients because they always come to me before I've read it but that have cured Alzheimer's disease so you know I think that's the nature of news and they want to take you know and it doesn't go into where the study was done you know how so I can say that this isn't a cure but at my age I'm I don't run down to the drugstore right away you know when I hear about these things so that would just be one comment not that it isn't really a great intervention but and now it'll come one day you know one of my patients will say to me I read about this and it cures Parkinson's and you know okay I need to look at this and then it really does cure Parkinson's so it'll come it will come by I haven't read the article so my my HuffPo and google it hasn't come to me for some reason but I will we will investigate it as I come to you know when you said British I wonder about stem cells they do a lot of stem cell in PD but nothing definitive yet a quick comment we don't know a heck of a lot of people with who who get Parkinson's go on to get Alzheimer pathology and Alzheimer's symptoms and have the two together I think they're they're too commonly Co associated for it to be a coincidence I mean I think maybe the miss folding of one protein triggers the miss folding of the others but it's a great question on which there's a way to a little research over here you're nice yet it seems like there's a really small proportion of early diagnosis and exercising but you're seeing some decline aren't you just going to get we like to be challenged do you wanna take a step yeah I my my thought on that is is is that it really is individualized I mean and as a as a physician when I'm seeing a patient and this is part of the reason why we try to spend so much time with our patients because I feel like I really have to get to know the patient or feel that there's trust mutual trust and and get a sense of why is the person there right maybe the person is there because he or she wants to make sure there's nothing going on right or maybe the person is in the clinic because they're absolutely convinced that there is something going on and to them receiving a diagnosis is a form of treatment really because you can close you know all these doubts that you have up as to what's going on so I completely get your point that you know from our side we want to see as many people as we can you know but on the other side I think all of us respect that a position right and we're very cautious as to you know but there's no formula to that it's all of it is like what happens in the room and how you feel it I agree yes I think we have time for one more question so I'm gonna yeah I have to take the challenge a little bit I like what you said too but um you know it depends on how much you know you want to live in uncertainty you know and you know I can tell you the other side of this which is most of my patients with frontal temporal dementia cause of lack of insight make catastrophic financial decisions that lead to bankruptcy for the family that cause car accidents that lead them to being arrested you know that's obviously not you but you know I think the you know the question is you know not number one do you wanna live in uncertainty can you brush it aside and put it away so that it's not a concern if not I would say are 98% of the time people are happy to know and people who come and say I don't want to know my father never wants to know he will you know hurt himself if you tell him almost never is that the case and I think you know if you're dealing with smart people who don't jump the gun on diagnosing bad things when they aren't there you know I think it's often very healing and you know we have stop demonizing these conditions you know it if you have mild cognitive impairment I you know I think it's um it's it's probably good to know start initiating plans around that being more vigorous and your therapeutic interventions their medicines that help a little bit so I'm not I'm not saying everyone benefits but I think a lot of people do from having more certainty about what's going on alright a challenge to yeah second baby so a lot of misunderstanding too and when we talk about early symptoms sometimes they might be unusual and we see a lot of families and relationships that get ruined by misunderstanding and thinking that a person doesn't care and that a person is become irritable and so there there is also a lot of misunderstandings that can happen in families and communities because of misinterpreted symptoms I think that's all the time we have it's been a pleasure thanks for coming [Applause] [Music] you

Channel: University of California Television (UCTV)

Views: 16,372

Rating: 4.8356166 out of 5

Keywords: dementia, alzheimer's, AD, neurodegenerative disease, brain

Id: cmlbaNdFoAc

Length: 89min 57sec (5397 seconds)

Published: Mon Jul 22 2019

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Neurologist Dr. Serggio Lanata explores the neurodegenerative disease of the brain, what they have in common and how they differ. alzheimer's is the most common neurodegenerative disease but there are several others including Parkinson's, Huntington Disease and others. Recorded on 04/23/2019. Series: "Mini Medical School for the Public" [7/2019]