The genetics of frontotemporal dementia

Published on July 1, 2014   41 min

Other Talks in the Series: The Genetic Basis of Neurological Disorders

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Hello. My name's John Hardy. I work at the Institute of Neurology at University College London. What I'm going to talk to you today about is the genetics of frontotemporal dementia. This is either the second or the third most common form of dementia after Alzheimer's disease, and afflicting about the same number of people who have dementia with Lewy bodies. It's a devastating disease, as I'll explain later, and really a major public health problem and, of course, social problem for those people who are afflicted with the disease.
The characteristics of frontotemporal dementia are that the frontal and temporal lobes of the brain are affected and show gross atrophy. It's responsible for about 10% of all dementias, and depending on the survey, affects somewhere of the order of 3 to 15 every 100,000 individuals. The reason there is this type of variability is because sometimes the diagnosis is rather difficult to make and because it can sometimes resemble Alzheimer's disease. Unless there is neuropathological confirmation, then prevalence rates can vary based upon the diagnostic criteria which are used. The onset age for the disease is typically in the late 50s or early 60s of age. I do know of cases where the onset age is from the 30s. And of course, it can afflict people in their 70s and 80s. But the typical ages of onset are, as I say, in the 50s and the 60s. High proportion, about a quarter of the cases, are familial. That means usually that people in the familial category have one of their parents who have had the disease. And of course, the grandparent on that side of the family can also have been afflicted. So sometimes, you can see the disease traveling down through many generations. It's a very variable disease in terms of its clinical presentation. Some people have language problems very early in the disease. They have difficulty speaking. They become what is known as aphasic, and they can't find words. Other individuals have personality changes very early in the disease process. And they can become either apathetic or rather disinhibited. A very frequent complaint of caregivers is that their loved one seems as if they're drunk in their behavior. They either become very quiet and almost mute, or they become very inappropriate in social settings. In agreement with this clinical variability, there is actually a lot of pathological variability. So I've described how the disease is characterized by atrophy of the frontal lobes or the temporal lobes of the brain. But the histopathology-- that means the pathology in the brain cells-- is also variable. And to some extent, though not perfectly, this pathological variability fits with what I'm going to tell you about the genetic heterogeneity and also fits to some extent with the clinical heterogeneity, as well.