One of my areas of interest is in an area called rapidly progressive dementias. There is no consensus definition of what a rapidly progressive dementia is but from my experience, I’ve been referred over 3000 patients with rapidly progressive dementia, and the way I define it is that when a person goes from normal cognition to dementia within usually weeks to months, but I usually use a cut off of about two years...
One of my areas of interest is in an area called rapidly progressive dementias. There is no consensus definition of what a rapidly progressive dementia is but from my experience, I’ve been referred over 3000 patients with rapidly progressive dementia, and the way I define it is that when a person goes from normal cognition to dementia within usually weeks to months, but I usually use a cut off of about two years. So, if they go from normal cognitive functioning to inability to function at their previous level within two years, I call that a rapidly progressive dementia. And there are many definitions of dementia but usually we say that somebody is impaired in one cognitive function, which could be memory, executive function (which is organizing, planning, multitasking), language, visual spatial function, some people would include behavior in that. If you’re impaired in at least one and sometimes two or more of those domains, to the point where you can no longer function the way you used to, that’s dementia. Some of my colleagues who do research in this field, they use slightly different definitions. One colleague, for example, doesn’t care how long you’ve had symptoms, as long as there’s a phase within your disease in which you have a rapidly progressive decline. The reason I don’t like that is that I think that’s a different group of disorders. The differential there would be different than from somebody who goes completely normal to dementia. I think that’s a useful definition for a different group of disorders, but not what I’m interested in.
I became interested in this field of rapidly progressive dementia when I started collaborating with my colleague at UCSF, Dr Stanley Prusiner, who won the Nobel Prize for discovering the prion protein and how it caused human and animal diseases. He was trying to recruit patients for a study called the Prion Detection Study. I started bringing in patients who were presumed to have prion disease and I found that about 25% of them who were referred for that study didn’t even have prion disease. And so I was very interested in how very smart doctors, well trained doctors, were making misdiagnoses. A few years later, we did a treatment trial for CJD, and one fifth, 20% of the patients were referred for a treatment trial turned out didn’t have prion disease. So, I realized that there was a hole in our medical education, particularly in neurology, about training neurologists and other physicians on how to work up a patient with rapidly progressive dementia. So that became an area of my interest, an area of that I wanted to work on in education. What should the differential be? What should you be thinking about when you see a patient with rapidly progressive dementia?
One of the mnemonics that I use, which I borrowed, I don’t even remember where I learned it in my education, was the mnemonic VITAMINS. Where V stands for vascular etiologies, I for infectious, T for toxic metabolic, A for autoimmune, M for mitochondrial, or could be metastases, the next I would be iatrogenic from medications or things like that, over medication use, N for neurodegenerative, and then S for systemic diseases, seizures, or psychiatric disorder. So whenever I’m presented with a patient who presumably has a rapidly progressive dementia, I actually sometimes go up and I write down that list, and I make sure that I’ve thought about all the etiologies. And it’s important because some of these etiologies are completely treatable, if not even curable. Currently, prion disease is incurable, as are almost really all neurodegenerative diseases. We don’t have a cure for them. So I always am looking for something that’s treatable and curable. For instance, this led to my interest in autoimmune encephalopathies, a large proportion of which are treatable. We can get improvement by giving immunosuppressive therapy to patients, but they’re also, in some cases, curable. Patients can go back to completely normal function and maybe never even have a relapse. So, that’s become an area of my interest. I’m trying to come up with better diagnostic methods, teaching at all different levels of medical education. And we’re trying to come up with better diagnostic tools in prion disease, for example, a lot of my research has been on the MRI features, the diffusion weighted MRI features in prion disease, and how these have sensitivity and specificity in the mid to high 90 percentile But you have to know what to look for.
