Early detection of Frontotemporal dementia (FTD)

okay and say thank you for the opportunity to tell you about some of the work that we're doing here in Oxford and actually here in the John Radcliffe and we're trying to find some of the earliest signs of frontal temporal dementia say frontal temporal dementia is a group of progressive and overlapping clinical syndromes that are associated with atrophy so that's brain shrinking in the frontal and temporal lobes so the images you can see there where you've got these increased dark areas are where the brain sort of shrinking in the frontal and the temporal regions and the robhan gave a nice introduction to dementia and the overall prevalence of it and it's not as common dementia as Alzheimer's disease but in fact in the younger age groups so 45 to 65 it's the second most common and dementia next to Alzheimer's disease and it's actually nearly almost as common so it's considered a young onset dementia and so we know the board sorry about this okay so we know there's sort of broad functions of the frontal lobes the frontal and the temporal lobes are affected in frontal temporal dementia hence the name and the frontal lobes you can see they're shown in blue and the broad functions of them are very much associated with behavior motivation impulse control and some important speech and emotion functions and because of this we can sort of predict the kind of symptoms we'll see an SPD and because of the functions of the frontal lobe so when the frontal lobe starts to atrophy we have symptoms associated with those functions the temporal lobes and that they're shown in the yellow and pink are very important how they are very important memory and language functions so again these are things that are affected in frontal temporal dementia so because of the functions of those loads we have some symptoms that we see in patients and one of the most the clearest symptoms is the lack of insight so patients often don't know that anything is wrong or that they've had any change in behavior and it's very often family members who report and changes so hyper orality is another one so that's the kind of fixation with the mouth and sort of seeking out sweet things in compulsive eating and lack of Hygiene and can be a problem so patients sometimes become quite apathetic and stop caring for themselves and there's also quite a few behavioral changes and that can can occur and this again is because of the functions of the frontal lobes that are affected so impulsivity some compulsive behaviors as a--they which can be quite difficult in families when people start to come quite apathetic towards the loved ones and also disinhibition and these are really the behavioral and variants of frontal temporal dementia there's also a language variant in which there can be problems with speech with production and comprehension of speech and with being able to name simple things and there's a picture of Carrie Jones who has primary progressive aphasia which is a type of variant of frontal temporal dementia that's associated with problems with them producing speech so I'm going to share with you just two case studies from some patients from our clinic and who probably let us share their stories and they will have been anonymizer discovered and and just to give you a sort of sense of how we can have very different presentations with this type of dementia and so elaine was a 59 year old healthcare assistant and she reported and progressive difficulty finding words when she was speaking she notices particularly on the telephone and at work where she was having problems pronouncing longer words such as drug names at interview her speech was effortful and distorted and she'd say things like sullivan instead of elephant and she could name a shirt but she called the cusp a and she has has troubled repeating words such as British Constitution and baby hippopotamus and she also had that's quite difficult actually to rebirth she also had trouble following multistage commands so if you ask her to pick up a pencil and put it underneath a sheet of paper she'd have trouble with both stages of that command and her family history was interesting because her mother and actually had frontotemporal dementia so John a 51 year old property lawyer he began to steal money at work and regularly listed mysterious expenses on his travel reimbursement forms that turned out to be the purchases of pornographic materials by the internet when questioned he claimed that used his corporate account for his wife would not find out about his sexual activity at the time that this was discovered they'd also been some complaints of sexual harassment from female colleagues and he eventually lost his job but he didn't bother to try to find another one he became increasingly apathetic at home and his wife and children said that over the years he just completely lost interest and stopped speaking to them he also developed a strong desire for potato crisps and gained 15 pounds interestingly his family history revealed that his father and his first cousin had both died of motor neuron disease and so in both those cases you can you can see very different profiles that are presented a frontal temporal dementia but also interestingly both had a family history and that's because that's important because we know around 30 to 40 percent of patients have a relevant family history and that's because we know that there are mutations in three genes that account for the majority of these these familial cases so that's not to say that anybody has SPD we'll pass it down to their family members because in fact still the majority of cases of what we call sporadic so they don't they're not necessarily related to a family history or any specific genes that we know of but these patients are quite important to our research because because these families have this inherited form of the disease we can study family members who have the gene mutation but haven't yet developed the disease themselves and that can help us define really early stages before we have symptoms presented for here in Oxford were part of Gen Z which is the genetic frontotemporal dementia initiative and this is a multi center longitudinal study of FTD that was started in 2012 it includes 25 research centers across Europe and Canada and we have around 600 participants already recruited so we're bringing in patients and their family members you have these gene mutations and we do some brain imaging and a lot of behavioral testing and we take some biological markers so just to give you a sort of idea of the design of this study so we have our STD frontotemporal dementia patients and they've already been tested and we know that they carry this gene mutation so their first-degree relatives then also have a chance of also carrying this mutation that's been passed on and so their siblings and their children and they might be relatives might be a mutation carrier or they might not and in either case we bring them in to do some studying if they're not carrying the the mutation and they act as our sort of healthy control and they're not likely to go on to get FTD if they are a mutation carrier they're usually many many years before any symptoms onset so we can study them longitudinally to see if we can find really any tiny early signs of things changing in their breaks behavior in their brain so we're interested in any changes that are early on so before the disease onset so the way that we've kind of tried to predict when their disease will onset is by taking the average age of onset within the family and then we look at how many years before that age that the family memories so for example if a mother develops SPD at age 50 and she has a son who carries a gene mutation who's currently 30 then we estimate that the son is around 20 years before the estimated age of onset of his STD now that's not to say that if somebody has STD at 50 that their children will get it at that same age and this is just our best sort of estimate at the moment until we get a better understanding of when the disease onset so we bring in our patients and our family members at a baseline point and then we see them again after a year and then again after two years and hopefully and if we get funding again through until five years because we really want to track them over a long period of time to see and if the disease is starting and how it's progressing and we take medical history we do physical exams we do very comprehensive neuropsychological testing and also tests computerized and tests of other functions and we take blood samples and number punctures and do some brain imaging as well importantly we don't disclose the genetic results to out for the family members they don't have to know they don't ever have to know and some of them don't ever want to know and we don't know the results either so it's all held completely blindly so that we've got no bias so when we do this we see that around five years before symptom onset so this is in our family members who are otherwise healthy but they have this mutation and it gives them risk of development developing STD we see some subtle changes in behavior some short-term memory attention executive function and language changes and this is five years before we see any symptoms at all and in fact in the brain imaging ten years before our expected symptom onset we can see shrinking in an area of the brain called the insula it's highlighted there in red and also in the temporal lobes and then five years of for symptom onset we start to see shrinking in the green area there the frontal lobe so that fundus health frontal temporal areas that are most affected in this dementia and then we compare that to ten years after symptom onset so once someone has had SED since for ten years we can see there's a lot of atrophy all over the brain there so the important part of this is that at the stage at which the atrophy has has spread more widely it's a lot harder to treat because there's there's been a lot of irreversible damage already so if we can get in a lot earlier then we might have more effective drug treatments to kind of either stop or delay the progression of the disease and so what are we hoping to find what we really want to find early in robust markers of STD onset so when people come into the clinic reporting symptoms it's often been many many years of changes in the brain that have gone on undetected and we really want to find those changes as early as possible so that we can stop the progression or at least delay it we also want to find a robust markers of disease progression so each case is very different and it's very hard to give people an accurate idea of what's going to happen in the future because we don't really know exactly how the disease progression progresses we also want to find the x for inferred treatment intervention so as I said before and as that other people have alluded to and getting in earlier is really the important thing to do - before any irreversible damage has occurred and then we also want to find some outcome measures for clinical trials so when we're developing new drugs how do we know that they're effective how do we know that they're working is it because they've helped some of the symptoms or is it because they've stopped some of that brain shrinkage their brain atrophy so if you have any questions and then please do come and see me or feel free to email us at memory and be the end of story see don't you Kay thank you [Applause]

Channel: Alzheimer's Research UK Thames Valley

Views: 85,388

Keywords: FTD, Dementia, research, oxford university, Frontotemporal dementia

Id: OmBKniKQ0iM

Length: 13min 27sec (807 seconds)

Published: Wed Mar 29 2017