Hi, everybody, and thank you for having me. I'm going to talk today about frontotemporal dementia, and we're going to go over the different clinical syndromes in which they can present and, you know, what are the different pathologies that underlie them. I have nothing to disclose, and I'm hoping that by the end of today's talk, you know, everybody will be able to identify the clinical representations of these degenerative diseases, mainly frontotemporal dementia, primary progressive aphasia, corticobasal syndrome, and progressive supranuclear palsy, understand the anatomy that underlies these and the pathologic substrate, and recognize how treatment care plans can be individualized for these different clinical syndromes. So I want to start with a patient case. This is a 76-year-old right-handed man that came to my clinic with difficulty taking care of himself for the past one and a half years. His daughter reported that he was unable to prepare food or attend to hygiene, unable to care for his cat. He was displaying some hoarding behavior and was socially disengaged, not seeing anyone, not visiting anybody, and he was having some difficulty speaking and communicating as well. They reported a lot of pauses during speech, and his voice has gotten more soft. On his exam, his affect was flat, and he was disengaged from the conversation. His voice was indeed pretty hoarse and strained, and he had impoverished speech with a lot of paraphasic error, meaning pronouncing words differently than how they're supposed to be. His left hand was swollen, and he had a high-frequency tremor in that hand with a left facial droop. And he had increased tone in the left arm with a reactive myoclonic jerk. And then his walking was slow and imbalanced. His knees were bent a little bit, and he was hunched over. When we were talking to this, his daughter was like, you know, oh, even when I was a child, you know, my dad, he didn't function properly, and so we called the ex-wife who knows him from before the daughter was born in order to obtain collateral information. They had been divorced for about 10 years, but we were able to get a hold of her. So she reported that he used to be a brilliant man and that there was nothing that he didn't know. He was witty, entertaining, charming, charismatic, and he spoke many languages and had a lot of empathy for people. She did mention that he had alcohol use throughout his life, and he also did a lot of drugs lifelong, including prescription benzodiazepines. And so when the kids were born, which was in his early 40s, he started distancing himself and displaying some of the behaviors that we heard about. He became narcissistic, writing things on his resume that weren't true, which he never did before. He spent his days sort of sitting outside in the sun and reading, lost some of his empathy towards his wife and his kids, and, you know, there were days that would go by where the kids wouldn't see him because he'd be in his room. His son's friends knew that he was, quote, unquote, weird, and he used to say rude and inappropriate comments to his kids and their friends. And he sometimes brought the same things in bulk and never used them, buying the same items sort of in large quantities. And the family assumed that a lot of this was secondary to his drug addiction and that this was affecting his behavior. In fact, leading, you know, after many years to him and his wife divorcing. In his family history, his father apparently had, quote, unquote, Alzheimer's disease. But when we asked some further question about the father, you know, he, there was also drug addiction on the father's side of the family. And at age 50, the dad started keeping lists and addresses of stores almost in an obsessive manner. He became a compulsive shopper, and he would walk around sometimes naked, you know, in his home, regardless of who's there. He ate a lot and became very heavy, which was a deviation also from his pre-morbid personality. And he was a chain smoker, but one day he ran out of cigarettes and just didn't smoke again. So this is the MRI of our patient. And, you know, you can see that in this right frontal lobe on these cuts, there is a lot of volume loss with sort of deeper sulci and thinner gyri. We see this in the orbital frontal cortex and the medial frontal and a little bit in the dorsal sort of part of the frontal cortex. But also we see some parietal volume loss as well, but primarily this like left frontal volume loss. You can notice how the ventricle, lateral ventricle is pretty enlarged, primarily in this left front part of the brain. So we referred the patient to our genetic medicine department, because we suspected that he may have had something that was brewing and going on probably since he was 40 years old. They received an FTD, he received an FTD panel that revealed that he was a carrier of a mutation in the programming gene, one of the genes that causes frontotemporal dementia. He was started on SSRIs and moved into a care facility. And currently there is ongoing palliative care discussions with his families. And his children have sought some counseling and genetic testing for themselves. So this brings us to our talk today. And I'd love for us to spend the next 30 or 35 minutes talking about frontotemporal dementia and introduce the different ways in which we think about neurodegenerative disease and the brain networks that they affect. And then I will dive into talking about frontotemporal dementia, spending the bulk of the time on the behavioral variant, and then moving to talk about the language variant and some of the motor variants. And we will end by discussing some of the genetics of frontotemporal dementia. So to begin, I would like to talk about our dementia syndromes. You know, they are really varied. And there are multiple clinical syndromes that present with different symptoms and according to which anatomy is affected. So for example, what we refer to as Alzheimer's disease is an amnestic syndrome that affects the hippocampus on both sides or one side of the brain. But we also have other syndromes like musculoskeletal atrophy, dementia of the new body disease, corticobasal syndrome, and the frontotemporal dementia. And all of these, as you see, sort of are defined by a particular part of the brain being affected more than the other parts of the brain. And that leads to the sort of specific presentation of the syndrome. And syndromes sometimes can be the presentation of one disease. For example, the amnestic syndrome as well as specific cortical atrophy and the gophenic variant of primary progressive aphasia, all of them are actually presentation of Alzheimer's disease. Dementia with the new body disease is a presentation of the new body. Richardson syndrome and corticobasal syndrome are both tauopathies that relate to accumulation of tau protein in our brain. But the corticobasal syndrome can also have or can also be caused by Alzheimer's disease and others. And frontotemporal dementia is really a chameleon and can be caused by multiple things, including Alzheimer's disease, tauopathies, and TDP-43. And this is just a slide to show you, this is courtesy of Dr. Bill Seeley at UCSF, to show you really the various different pathologies that can cause the different syndromes that we have. And today we'll focus primarily on BVFTD and some of the primary progressive aphasias. But you can see even in BVFTD, all the different color bars are the different pathologies that can cause it. And so FTD really is an umbrella of illnesses that on a biologic, pathologic level encompasses multiple different diseases that have multiple biologies and probably need to be treated in different ways, even when they present similarly. So why is there so many variations? You know, we know from some studies in imaging that different degenerative illnesses like Alzheimer's disease, BVFTD, semantic dementia, so on and so forth, they present over anatomies that are very predicted and that there are anatomies that correspond with normal networks in younger, healthy individuals. So this is imaging from healthy controls that are in their 20s, you know, that are college students, where we are able to identify various networks of the brain that sort of activate and deactivate together when we do what we call a resting state functional MRI. And these networks happen to correspond with the atrophy pattern or the volume loss pattern of various different degenerative diseases, really demonstrating that degenerative diseases occur along brain networks that are very predictable and that are responsible of, you know, various tasks and functions. So with that in mind, I'm going to dive directly into frontoparal dementia and start by talking about the behavioral variant. Frontoparal dementia was first described in 1892 by Pick. It is the second most common dementia in patients that are younger than 65 with a prevalence of 15 and 100,000 in the age group of 45 to 65. It's also the third most common dementia in the elderly after Alzheimer's disease and Lewy body disease. And the age of onset generally is between 50 and 60 years of age. The survival can be short and may average about six years. How do we define frontoparal dementia? It's really a group of clinical syndromes that are due to either frontal and or temporal lobe dysfunction with relative preservation of the posterior brain structures. The clinical presentation usually is slow and assiduous, and the predominant symptom can be either behavioral, in which case we can call this behavioral variant frontoparal dementia, or language, in which case it's primary progressive aphasia, or an executive function impairment or motor impairment. And so this shows you how the predominant symptom can be different, and then your diagnosis clinically will be a different diagnosis, whether it's BVFTD, PPA, corticobasal syndrome, or progressive supraventricular palsy, which we will talk about these four categories in detail. The BVFTD or behavioral variant frontoparal dementia is the most common subtype. It often presents to psychiatric clinics or to marital counseling therapists because it causes personality changes that could be misunderstood by the family as being some interpersonal issues between the family or relationships. There are six cardinal features to behavioral variant frontoparal dementia. These include disinhibition, apathy, loss of empathy, obsessive-compulsive behavior, hyper-orality, and executive dysfunction, and we'll talk about each one of these in detail. Disinhibition is often the presenting symptom. An example of this is people being overly friendly, approaching strangers and starting conversations that are either too personal or too explicit. They may have excessive trust in strangers and with a difficulty in making sound judgments, and that really puts them at risk. They are vulnerable to exploitation, either sexually or financially, by other people. They may be subjects of online or telephone pranks, and the anatomy of disinhibition is thought to be related to atrophy or volume loss in the orbitofrontal cortex, that's the part of the brain that's right above our eyes. Apathy is also a very common symptom in BVFTD, and it is defined as social withdrawal but also decreased motivation. Examples include decreased interest in previous hobbies, general attitude of indifference towards topics, losing jobs and not seeking to work again. The anatomy is thought to be multiple because there are different types of apathy, but it can relate to either the right dorsolateral prefrontal cortex, the right ventromedial superior frontal gyrus, or the right anterior cingulate gyrus. All of these are in the frontal lobe. The right codate can also play a role. Loss of empathy can occur and people can be described as becoming more self-centered and losing the ability to understand the feeling of others. Examples are making rude remarks or gestures without regards to other people's feelings, being insensitive to someone else's illness or injury. They can be emotionally distant and detached, and this can create toxic dynamics for couples. People can become less affectionate and less involved in their children's schooling or upbringing. Keep in mind that the age of onset of BVFTD can be young, so at 40 or 50, and so people may have children that they are raising. The anatomy of the loss of empathy relate to right anterior temporal structures as well as medial frontal regions. People with BVFTD can also have obsessions or compulsions, such as being obsessed with specific thoughts or displaying compulsory behavior. Some examples include repetitive picking, chewing, lip-smacking, pacing, walking around. They can have constant blocking or unlocking or hoarding behavior. They can become mentally rigid, where they are less flexible to changes in plans or routine, or exercising at a very specific hour every single day, so on and so forth. The anatomy of this is related to the left lateral temporal and the basal ganglia. Hyperorality is the symptom of sort of overeating or eating too much, and they have difficulty in refraining from eating even after they have achieved satiety. They also can start displaying changes in diet, where they may crave sweets or eat non-food items. It may result in weight gain because of that, and it can also manifest in excessive drinking of alcohol or excessive smoke, even when they didn't have that before. So one point to make here that, you know, a new onset, you know, alcoholism, or sort of abuse of alcohol in older adults, you know, may be an indicator of a neurologic disease and sort of should be at least investigated to make sure that that's not the case. The anatomy of this relates to the right orbital frontal cortex, the insular region, striatal region, but also the posterior hypothalamus as well. And finally, executive dysfunction occurs in people with BVFTD. Well, that shouldn't suggest that other cognitive problems cannot occur. So often there is a misconception that memory problems, you know, don't exist, or sort of are less likely to occur in behavioral bad foot-to-pole dementia, but that's not necessarily the case, and many people can have memory problems. However, executive dysfunction is more predominant, and, you know, it's defined as difficulty with things like planning, organizing, problem-solving, so on and so forth. And the anatomy, you know, can be different depending on the exact symptom that they have or the exact sort of manifestation they have on neuropsychological testing. So how do we diagnose BVFTD? These are the international consortium criteria from 2011, and possible BVFTD is diagnosed if your patient displays at least three out of the six symptoms that we just discussed. And this becomes probable BVFTD when, in addition to this, they also have functional decline as well as imaging results that is consistent with behavioral bad foot-to-pole dementia, meaning displaying frontal or temporal lobe volume loss. Of course, the exclusion criteria is whether the deficits are better accounted for by other disorders or that you have biomarkers of some other illnesses that are causing this. Now, foot-to-pole dementia, or BVFTD, can also present with motor neuron disease, such as ALS or Lou Gehrig's disease. When this occurs, we call this FTD-MND for frontal-pole dementia with motor neuron disease. Patients with this disorder, they have the typical features of BVFTD either preceded or shortly followed by also typical features of ALS or motor neuron disease. One important thing to keep in mind here is that they may lack the weight gain that comes from overeating, because even though they may overeat or have hyperorality, they are losing muscle mass, and that translates into loss of weight for these patients. Patients with FTD-MND have the highest frequency of psychotic symptoms, including delusion and hallucination, as well as familial frontal-pole dementia with MND correlate with an expansion in the C9 or F72 gene, which we will talk about at the end in our genetic discussion. So what are the different pathologies that cause BVFTD? As you saw from the previous slide with all the nice colors, there are various pathologies. So frontal-pole dementia is, when we refer to the pathology, we call it frontal-pole lobe degeneration, and it can come with tau deposition that are differentiated between 3-repeat tau, which we call Fick's disease, or 4-repeat tau, which are corticosal degeneration and PSP, and we're going to also talk about these two in detail later. But also frontal-pole lobe degeneration can come with accumulation of a protein called TDP43 or TARD-DNA-binding protein, and these have three types, type A, B, and C, each type associated with different genetic factors, with type C being the least likely to be genetic in nature. And then FTLD-FUS is a genetic disorder that occurs in early age, usually earlier than 40 years of age. So how do you predict the pathology for FTD? It's difficult, but there have been some studies showing that some symptoms can correlate more with one pathology to another. For example, people who binge eat are more likely to have FTLD with tauopathy, you know, according to a clinical pathologic study that was done in 2017 by David Perry. But also people with Fick's disease specifically may have early loss of empathy early on in the disease with lack of warmth. People with 4-repeat tauopathy, if they have CBD, they may have apraxia on exam. If they have PSP, they may have a history of falls or dysphagia, meaning difficulty swallowing, or dysarthria, difficulty speaking. People with FTLD-TTP inclusions may have a lot of delusions, as well as signs of motor neuron disease. The type A has a lot of delusion, type B may have delusion and hallucination, and type C may have a lot of language symptoms, as well as difficulty recognizing faces, or what we call prosopagnosia. And as we discussed earlier, FTLD-FUS can occur really early, younger than 40 days of age. On imaging, there also could be some differences between that can predict the pathology. People with 3DP tauopasies or Pick's disease have the most severe volume loss on the MRI. People with CBD can have volume loss in the supplementary motor area that's around the motor cortex and the brain, and less so in the anterior temporal lobe. People with PSP also do not have a lot of atrophy in the temporal lobe, and they can have features of PSP, such as the hummingbird sign, which I will show you later today. People with type A TDP pathology can have findings on MRI that are unilateral, such as our patient who has programmable mutation and he probably has type A FTLD-TDP, the patient that we present. If you remember, he had just a right-sided frontal and parietal volume loss. Then people with type C FTLD-TDP pathology can have asymmetric right anterior temporal lobe volume loss. Finally, people with FTD may also display behaviors that could be misconstrued as criminal. Up to 37 percent of patients have behavior that could be construed as criminal, and 14 percent of them are at presentation. These behaviors include theft, traffic violations, sexual advances, trespassing on other people's property, and public urination. This is based on a large study that was published in 2015 and that looked at comparing these criminal behavior in people with FTD and Alzheimer's disease. Finally, the treatment of VVFTD can be multidisciplinary. There is no disease-modifying treatment as of yet that we can offer, so no cure. There are some clinical trials that are recruiting for some conditions such as people with a programmable mutation. Education of patients and family about the disease is really key and pointing them to support groups, home health aides, daycare centers can be helpful. For the behavior symptoms such as disinhibition and apathy, we can try to treat them with SSRIs. The evidence is scarce. Paroxetine has been studied for agitation and behavioral symptoms, but it has a lot of anticholinergic side effects, which usually we try to avoid in people with dementia. We sometimes can use citalopram, which was studied at 30 milligram dosage, which as this group knows is black box at this dose. Trazodone may be helpful for agitation and hyper-eating at 150-300 milligram dosage. Antipsychotics may be used for agitation and disinhibition with, again, very little evidence. Some of the evidence that we have is for olanzapine and risperidone, which of course can result in extrapyramidal side effects when used. Moving on to the group of primary progressive aphasias, which is still classified on the frontopral dementia. This is a group of disorders where the primary problem is in language or progressive decline in language abilities. In fact, the criteria require that the initial two years have primarily language problems with relative sparing of other cognitive and behavioral domains such as memory, visual spatial symptoms, so on and so forth. Language should be the primary symptom that greatly influences virtually all other cognitive functions. There are three subtypes that we'll talk about in details. This is all patients that have primary progressive aphasias and where the atrophy or volume loss is on their MRI. But when you divide them into groups of patients that look alike, you really have three groups that emerge. One group with more frontal volume loss, one group with more temporal volume loss, and one group with more parietal temporal volume loss. We'll talk about these three groups. The first group is referred to as non-fluent variant primary progressive aphasia. These are patients that have difficulty in speech production, which can take the form of agrammatism, meaning problems with the grammar of sentences, or motor problems such as effortful, slow speech, as well as apraxia of speech, which is difficulty in initiating or distorting the sounds or the syllables that you're trying to pronounce. Sometimes deleting some syllables or adding syllables that shouldn't be there. Patients with this are usually aware of their deficits and they are very frustrated because of that. They are the most likely to have also motor findings such as rigidity, slowing of their movement, reduced dexterity, and usually this happens at the right arm because the disease affects the left hemisphere. The anatomy is in the left pericelvian region as well as the opercular region. Opercular means hat in Latin, and so it's the hat of the insula. It's the part of the frontal lobe that's really above the insula or covering the insula. The pathologies that can cause this include PSP, critical pathology generation, as well as frontal temporal lobe degeneration type A with TDP. This is an MRI from a person with non-fluent variant at year 1 after a symptom onset and at year 4. You can really see how this is the insula and that's the frontal lobe that's covering it what we call the opercular region. Over four years, we have a lot of volume loss and the insula is now almost exposed and it has lost its hat because of volume loss. Moving on to the semantic variant, and it's left predominant form meaning affecting the left anterior temporal lobe. People lose progressively the knowledge of words and objects. They can literally lose vocabulary and meaning of words as well as looking at an object and not knowing what it is. They continue to have very fluent speech and may have what we call surface dyslexia, meaning reading words in their phonemic way, not necessarily in how they're supposed to be read. Like for example, bouquet can be read as bouquet because that's how phonetically it would be. The speech may be impoverished and contain very non-specific words like thing, stuff, animal. They may ask a lot about meaning of words, and they usually exhibit no motor findings. This disease can spread to the other temporal lobe within the three years, and then within seven years can spread to the frontal regions. It's usually almost exclusively associated with TDP type C pathology, but some people can have Alzheimer's disease and have the same. This is an example of this MRI of a patient where you can see the left anterior temporal lobe volume loss as compared to the right. You see a lot of empty spaces here in the dark, a larger temporal horn of the lateral ventricle, all showing volume loss in the anterior temporal lobe on the left side. Finally, the logopenic variant is the third PPA. This is not a frontoparal dementia because it affects posterior structures, not frontal or temporal structures. It is a problem in language that has to do with difficulty processing the sounds of language, what we call phonologic processing. People can present with word-finding difficulties and slow and syntactically simple speech. They also have a lot of difficulty repeating sentences because repetition depends a lot on our ability to hear and process the sounds of what we heard. They have also difficulty comprehending longer sentences, so they need shorter or less sounds in order for them to understand better communication. Then we also have difficulty with calculation, because calculation happens very near to where the area of the brain where the volume loss is for this disorder is. The anatomies and the angular gyrus are what we call the parietotemporal junction in the left hemisphere. Most everybody with this has an underlying diagnosis or pathology of Alzheimer's disease. Then moving on to our last two syndromes, both of which have a lot of things in common and they can cause executive problems along with motor symptoms. Corticobasal degeneration and progressive supranuclear palsy, or CBD and PSV are the acronyms, have a lot of things in common. Both of them can denote the name of a clinical syndrome as well as the name of an underlying pathology. Both of them, when you refer to the clinical syndrome manifests with motor symptoms. Both of them, when referred to the pathology, are four-repeat tauopathies, can cause typical BVFTD, and they can also cause non-fluent venipar because of aphasia. Both of them can also cause the corticobasal syndrome, which we'll discuss what that is. I know it's confusing. Corticobasal degeneration was first reported by Herbes in 1968 on three patients that had a progressive disorder of movement and posture, which wasn't Parkinson's disease. He described the pathology of swollen neurons with aggregates of tau proteins. Initially, it was classified under Pick's disease because this is the only tauopathy that was thought of as a degenerative disease at the time. However, after time passed and we started learning more about this, we noticed that only 50 percent of patients that are diagnosed with this clinical corticobasal degeneration actually had corticobasal disease pathology as per these criteria, the swollen neurons with tau proteins, and the other patients had other things like Alzheimer's disease and other pathologies. Brad Bouvet at the Mayo Clinic introduced the nomenclature corticobasal syndrome in order to distinguish between the clinical syndrome of progressive disorder of movement and posture, and the pathology of corticobasal degeneration related to tau protein. This very important paper from 2011 by Suzy Lee really taught us about the different manifestation of corticobasal degeneration. The pathology, the tau pathology of corticobasal degeneration can present with the corticobasal syndrome, but also can present with language disorder, non-fluent variant of PPA, can present with behavioral variant of multiple dementia, and it can present with posterior cortical atrophy, which we didn't talk about, but this is a syndrome that affects our visual-spatial processing. Then on the other hand, the corticobasal syndrome, which is defined as progressive motor syndrome that include limb rigidity, limb dystonia, or limb myoclonus, with either orobuccal or limb apraxia, corticosensory deficit, or alien limb syndrome. All of these are various syndrome that denote difficulty in the tone of our muscles, whether they shake on their own, apraxia meaning difficulty in planning a movement that we know really well, such as how to flip a coin in the air or how to brush your teeth. Corticosensory deficit is not being able to put together sensory information to process it, and alien limb syndrome is when your limbs do things that are not under your control, such as start floating up in space. This corticobasal syndrome can be caused by multiple pathologies, with CBD being one of them, but Alzheimer's disease being a very common pathology underlying corticobasal syndrome, as well as some others like PSP or mixed pathologies. The management of corticobasal syndrome, similar to BVFTD, there is no cure, and the treatment for the individual symptoms can be challenging. There is some evidence that perhaps levodopa may help with rigidity and bradykinesia, but this is really unclear and again, not great evidence there. Dopamine agonists have been studied with conflicting evidence. Cholinerase inhibitors may delay the symptoms if we think they are pathologies of Alzheimer's disease. Occasionally, Botox is used for symptomatic relief of the rigidity, especially if there is pain from the dystonia. Again, education, counseling, and support is important for management. Now, PSP as a clinical syndrome, usually when we say PSP and we say nothing else, we mean the Richardson's syndrome or the Richardson-Olszewski syndrome described in 1964. This syndrome is one in which there is progressive difficulty with balance and frequent falls, as well as supranuclear ophthalmoplegia, meaning difficulty in moving our eyes, usually starting with down gaze looking down, but then affecting other directions such as looking up or looking to the sides. But again, similar with CBD, later reports found that there's a diversity in the clinical syndromes that PSP presents. PSP can present with the syndrome of frequent falls, but can also present with language symptoms such as the non-fluent variant of prime vagus of aphasia. It can present with Copernicus syndrome, as we just discussed, and with frontoparal dementia. PSP can be a short disease and the median duration of the illness from the onset is about six years, with the median survival after diagnosis is 1.8 years, with mostly aspiration pneumonia being the reason of that. Often on imaging, we can see the midbrain volume being small and correlating with scales of how we measure PSP, which I'm not going to go into today. When the midbrain volume is less than 14 millimeter in diameter, which I'll show you on the next slide, it can be associated with PSP. That's when we see what we call the hummingbird sign. This is the brainstem here. As you can see, the midbrain is relatively small compared to how large the diameter of the pons is. Then this gives the illusion of having the head of a bird with a big belly of the hummingbird, and then the beak here. We call this the hummingbird sign that we can see in people with PSP. Again, the management can be tricky. A trial of carbidopa levodopa can be helpful early on for bradykinesia and rigidity, but the evidence comes from case series, and it's unclear that that can help everybody. Triple threat therapy, including physical therapy, occupational therapy, and speech therapy, can help with these patients, including doing a swallowing evaluation. Sometimes coenzyme Q10 have been shown to have a trend towards slower decline. Unclear if it's helpful or not, but it's not harmful, so something that we could try. It's unclear yet whether tau-clearing agents can be helpful and research is ongoing to see whether agent that can help clear the tau accumulation in the brain can help with PSP symptoms. Again, the progression can be fast over 3-6 years following diagnosis. Finally, I want to talk about genetics real quick. FTD, a large proportion of patients with FTD can have a family history, up to 40 percent. About 10 percent, which is one in 10, can have an autosomal dominant genetic heritability. Maybe FTD by far has the largest proportion of familial cases as compared to PPA, probably because of aphasia or Cotyglobus syndrome and PSP. There are three main genes that we're going to talk about today, although there has been a lot more genes now that have been identified in the past 7-8 years. MAPT or the microtubule-associated protein, tau gene, is located on chromosome 17. The mutations in it is seen in 3-14 percent of patients with clinical BVFTD. There is a founder effect in the Netherlands, and the typical age of onset is usually at age 50. The progranulin gene or GRN, which is the gene that our patient that we presented at the beginning of the talk has, is also present on chromosome 17. The mutation can be found in up to 60 percent of cases of BVFTD, with 8 percent of all familial forms of FTD. The age of onset can be around 62 on average, but also can be later. Keep that in mind because that's one of the mutation that even though people can present an older age, they still have it. It may cause asymmetrical degeneration on the MRI, and you can see one hemisphere having more volume loss than the other. But also people can have Parkinsonian features. If you remember, our patient had that on exam, and he had rigidity and myoclonic jerks and difficulty moving his left arm. These can be mistaken for Parkinson-like or Parkinson's disease, but in fact, they are not, and they're related to this gene. Then finally, expansions in the non-coding region of the gene called C9RF72, which it's called after its location. It's located on chromosome 9, on the open reading frame 72. This is now the most common genetic mutation. In familial FTD, up to 11.7 percent of cases of familial FTD, but also familial ALS, even without FTD, which is about a quarter of the cases. The age of onset on average is age 60, and people with this expansion can have a higher prevalence of delusions compared to people who don't have the C9G expansion. Then they can have cerebellar involvement on imaging where there is volume loss in the cerebellum, as well as the thalamus can be involved on imaging. With this, I'm bringing my talk to a conclusion, and just a few take-home messages for everybody. Neurodegenerative conditions really present themselves in various clinical syndromes, usually dictated by the underlying brain anatomy of the disease. Today, we talk primarily of the frontoral dementias and how they present. When the frontal lobe is involved, a patient can present either behavior, language, or motor executive clinical syndromes, as we discussed. FTD encompasses a group of syndromes that include behavioral ventral-temporal dementia, primary progressive aphasia, corticobasal syndrome, and progressive superior peripheral palsy. The treatment for these remains centered around symptomatic relief, wherever possible, support, and anticipatory guidance and education for the family and the patient. Predicting the underlying pathology helps us inform the patient about what to expect, so doing anticipatory guidance with them. It might be important in an era where we are slowly inching our way towards disease-modifying therapies that are being developed in research. So thank you so much. Really appreciate my time here and happy to take any questions. Thank you.

frontotemporal dementia

clinical syndromes

primary progressive aphasia

corticobasal syndrome

progressive supranuclear palsy

genetic factors

multidisciplinary care