TCPR: As a neurologist, how do you approach the evaluation of dementia symptoms?
Dr. Small: I think of the causes as fitting into four categories: toxic/metabolic, structural lesions, psychiatric illness or neurodegeneration.
TCPR: How do you go about evaluating these possibilities?
Dr. Small: To rule out toxic metabolic causes of dementia, I will typically check a B12, folate, thyroid levels and RPR [rapid plasma reagin test for syphilis]. If there is something in the clinical picture that makes me worry about Lyme disease, liver toxicity or HIV, I will test for those as well.
TCPR: How do you assess for structural lesions?
Dr. Small: I’ll typically order a structural MRI or a CAT scan if I suspect structural lesions. I’m looking for anything in the brain that ought not be there and might be compressing or damaging areas involved with cognition. Generally, tumors, large strokes and hydrocephalus are picked up on a good neuro exam, so what I’m really looking for on these imaging tests are small to moderate strokes. Stroke is extremely common, and often people have silent strokes, and this is something we can see well with structural MRI.
TCPR: How do you test for neurodegeneration?
Dr. Small: Neurodegeneration includes the most common causes of dementia, and these have no real diagnostic test. We make the diagnosis by excluding the other categories I mentioned. Once we have determined that the cause of dementia is neurodegenera- tion, we have to sort through all the types—not only Alzheimer’s (which is by far the most common), but Lewy Body degeneration or frontotemporal degeneration, both of which commonly present with psychiatric symptoms.
TCPR: How do you determine which type of neurodegeneration you’re looking at?
Dr. Small: We try to identify what areas of the brain are most affected, because although they share some pathogenic background, these disorders are fundamentally different in the areas of the brain they target. So, for example, Alzheimer’s disease starts in the hippocampus, and the main characteristic of hippocampal-dependent memory loss is difficulty in encoding new information, not retrieving old information. The typical patient with Alzheimer’s can’t remember what happened yesterday but has an easy time talk- ing about events that happened years ago. Of course, the most helpful way to identify the areas of the brain involved in memory loss is still brain mapping.
TCPR: And what is the best method of brain mapping?
Dr. Small: The most time-honored technique is neuropsychology. A very skilled neuropsychologist will take three or four hours in order to “interrogate” different parts of the brain, much like an engineer approaches a broken machine.
TCPR: What valuable information do you typically obtain from neuropsychology testing results?
Dr. Small: First, it helps us determine if a patient’s cognitive impairment is just normal aging, and second, it can identify a pattern of impairment. Although it is rarely clear cut, such testing might show a pattern more consistent with a medial temporal lobe prob- lem or the posterior cortex, for example.
TCPR: When do you turn to neuroimaging such as functional MRI?
Dr. Small: Functional MRI (fMRI) is similar to positron emission tomography (PET) in that it allows us to measure neural activity in different parts of the brain. Although neither technique can actually diagnose dementia, I still use them and I think a lot of clini- cians do. If I see severe atrophy in the medial temporal lobes, for example, and I was teetering on the edge of an Alzheimer’s diag- nosis, this information is very useful.
TCPR: Can you give us another example of when you might use neuroimaging for diagnosis?
Dr. Small: A good example is for a patient who may have Alzheimer’s or frontotemporal dementia (FTD). We’ll order a PET or SPECT study because these types of neurodegeneration show different patterns. If it’s FTD, we'll see lower metabolism in the frontal lobe area. And because the frontal lobes are affected, these patients have behavioral problems—such as violence or mood swings. These are not things you see early on in Alzheimer’s disease.
TCPR: So if you are able to determine from an imaging test that a patient has FTD, what does that do for the patient?
Dr. Small: Unfortunately, it really only helps by suggesting the right diagnosis. There is no treatment for FTD. We are able to inform the family what to expect and how to manage it, but we can’t give medication or anything curative.
TCPR: What does the future of neuroimaging hold for dementia?
Dr. Small: Researchers are trying to develop variants of high-resolution fMRI that look at the first areas of the brain that are affect- ed by Alzheimer’s. With fMRI, SPECT and PET, the goal is to detect cell thickness early on. Right now they’re testing PET scans using an imaging agent called PIB—Pittsburgh compound B. This compound can identify plaques and tangles in the brain. It’s still in the research phase, but it’s very exciting to think we may be able to identify the precursors to Alzheimer’s disease before a patient has obvious symptoms. These new technologies may actually someday allow us to diagnose Alzheimer’s early.
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