Bruce L. Miller, M.D., is a Professor of Neurology at UCSF where he is the clinical director of aging and dementia and is the A.W. & Mary Margaret Clausen Distinguished Chair. Additionally, he is the Medical Director for the John Douglas French Foundation for Alzheimer's Disease where he has worked for the past decade. Dr. Miller is a behavioral neurologist with a special interest in neuroimaging and cortical function. In his dementia work he has discovered a small, but remarkable subset of patients in whom visual or musical creativity emerges despite the progression of language and social impairment. These extraordinary patients offer a window into the brain basis for creativity. Recently this work has been published in the journals of Neurology, Archives of Neurology, Journal of the International Neuropsychological Society, Brain, Lancet and British Journal of Psychiatry. Dr. Miller has noted FTD patients suffer from profound scrotonergic deficiency. Medication trials with these patients have started and the drug trials are among the first ever for patients with Frontotemporal Dementia. Dr. Miller also participates in drug trials for Alzheimer's disease which are sponsored by the National Institute of Aging, and private industry.
FCA: Can you explain briefly, in layman's terms, what frontotemporal dementia (FTD) is?
Dr. Bruce Miller: Frontotemporal dementia is a degenerative disease that affects the anterior portions of the brain. It's slowly progressive and leads to gradual loss of functions in the frontal lobes and anterior temporal lobes. It is often a genetic, familial disease and in approximately 40 percent of cases it is inherited like a dominant gene. So, if a parent had it in such families then about 1 in 2 of the children are likely to become sick with the illness.
When you ask for a family history, would most people have considered the illness to be Alzheimer's disease or some form of dementia rather than inherited?
In other cases, people think of it as being a primary psychiatric problem. So, in some of these families you hear that their father had alcohol dementia or was criminally insane or committed suicide or had some sort of psychiatric illness that was not considered a dementia.
How many people in the US are believed to have FTD?
It is very hard to determine an exact prevalence for FTD because I think that until recently it has been misdiagnosed and ignored by most people in neurology and psychology. So many of these people were considered to have a primary psychiatric problem or a problem that was due to Alzheimer's disease. But researchers in Europe that have focused on this particular illness see that somewhere between 10 and 20 percent of their dementia cases are due to this particular disorder.
Is there an average age or typical age at onset?
In our experience the average age (when the patient sees a physician) is around 56. It is an earlier onset dementia.
What symptoms would prompt someone to see a physician?
We see a variety of symptoms, with the most common I think being apathy -- a loss of drive, social withdrawal, lack of concern. The other major symptom we see is disinhibition. These people commit antisocial acts that suggest that there's been a dramatic change in their personality. So we've seen theft, hit and run accidents -- things that these people never would have done prior to the illness. We think that because there is a loss of brain serotonin, many experience weight gain or very disabling, repetitive compulsions.
For example, we had one gentleman who shaved his face constantly, over and over again, every day. In others we see repetitive urination or constant collecting of things. These are some very odd, ritualistic, repetitive behaviors that we see.
How does FTD differ from other dementias like Alzheimer's?
In Alzheimer's, the first symptom in close to 80 percent of people is memory loss. With FTD memory loss is unusual as a first symptom, more likely you're going to see loss of speech or language or these behavioral changes.
As the disease progresses, what are the differences between the two or do they eventually appear to be the same?
I think in the later stages of the disease the patients can be hard to differentiate because Alzheimer's disease spreads anteriorly and frontotemporal dementia spreads posteriorly so eventually patients with both illnesses look very similar. But I think in the earlier stages we have a much better chance of differentiating them. The other thing that is peculiar to frontotemporal dementia is that a number of these people end up getting Lou Gehrig's disease (ALS). So there is a very strong association between frontotemporal dementia and ALS. About 15% of our population at UCLA either got ALS or had a first degree relative with ALS. So this suggests that there is a vulnerability of the frontal neurons and the lower motor neurons for reasons we don't quite understand yet.
How do you diagnose FTD?
Diagnosis is a combination of history, neuroimaging and neuropsychological testing. Often, the history suggests early onset changes in personality, weight gain, and the repetitive compulsive behaviors. Neuropsychologically, we see the loss of frontal executive function or imaging atrophy in frontal regions. Neuropsychological testing tends to show sparing of memory, sparing of visual spatial skills, which you know are the first deficits in Alzheimer's, and quite marked problems with frontal and executive type tasks.
Are there any treatments?
We have treatments for the behaviors but nothing at the moment to slow down the illness or improve the psychological function. So, a lot of these patients benefit from selective serotonin reuptake inhibitors. Some of them require some of the newer anti-psychotic agents. The older type of anti-psychotics that block dopamine are dangerous in these patients because many of them have Parkinsonism. Therefore, adding a dopamine blocker can be lethal. I think another aspect of treatment is having the caregivers get help and having someone to come into the home to spend time with the patient and take some of the huge burden off the primary caregiver. This is even more difficult than Alzheimer's disease where you don't tend to get these behavioral troubles until later in the illness.
Do you have any other suggestions for family members coping with the behaviors?
It is important to realize that it's not the patient's fault. It's not something that they are trying to do. Caregivers should get help and not try to take on everything themselves. It is good to get someone to walk with the patient. Making sure that they're up in the daytime getting exercise helps prevent them waking up in the middle of the night.
What do you see on the research horizon?
I think what has been very exciting is that people including our own Kirk Wilhelmsen at UCSF have found mutations in the gene that makes the protein tau. So these tau mutations at least seem to explain some of the familial cases. I think one of the very exciting things that have happened only in the last year is that there are now some mice that have these tau mutations and get sick and we can now begin to test medications in these mice.
What kind of timeline does this type of research and testing take and when would it go to human subjects testing?
I think you never know. It could happen very rapidly and our hope is that something very exciting will come soon. I think realistically it might be as long as 5 to 10 years.
Can FTD patients stay in the home?
I think they can --it depends on the family and quite a bit on the behaviors. I've had some remarkable families that have cared for the patient at home until the time of death and others have really required nursing home care. I think it varies.
Are there any other common misconceptions about FTD that you'd like to comment on?
My first experience with this came from research I did in patients that developed psychiatric disease for the first time later in life. So we were studying patients who developed late life psychosis. I think that some of these patients in retrospect had frontotemporal dementia. Therefore, a dramatic change in personality, behavior that looks psychiatric may be FTD.
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