TCPR: So we’ve done the labs and neuroimaging and nothing jumps out in terms of comorbid depression, or substance abuse, or anything else that’s obvious. You now have a patient with some degree of cognitive impairment but no clear cause. What’s next in the evaluation?
Dr. Agronin: Neuropsychological testing is pretty much the gold standard in terms of knowing whether there is any significant cognitive impairment and what is the extent of it.
TCPR: Do we send everyone who comes in complaining of memory issues to neuropsych testing?
Dr. Agronin: Not necessarily. If I meet with someone and find that there is just mild intermittent forgetfulness and they are very articulate about what they are forgetting, I am less concerned. I am more concerned about someone who is not aware of forgetfulness, or not aware of being repetitive and the informant is telling you that, or you are seeing changes outside of memory such as word-finding difficulty, disorientation, visual-spatial changes—I would order testing in any of these kinds of patients. But even if you decide to hold off on neuropsych testing, I would reassess what is going on after three to six months and if there are persistent problems or changes, then I think you are obligated to get a neuropsychological profile done.
TCPR: And what are you likely to find on neuropsych testing?
Dr. Agronin: Technically speaking, neuropsychological testing should show that they are at least about a standard deviation below their peers as the formal criteria for mild cognitive impairment (MCI). In practice, if we see someone who has persistent memory changes that are a nuisance but they are still functioning pretty well, we usually will label that MCI as a provisional diagnosis, with or without testing.
TCPR: Let’s say the neuropsych testing comes back a standard deviation below the norm and the report says something about mild cognitive impairment. How do you communicate that to the patient without being overly alarmist while at the same time providing an accurate picture?
Dr. Agronin: I meet with them and I basically lay all the puzzle pieces out on the table. I will recap the history that they reported to me, factor in any medical issues, any medication issues, and psychiatric issues that might be a concern and what the neuroimaging showed. I will then bring in the neuropsychological test results and we look at the big picture and I will give them an impression based on that. I may say, “When we look at your history of slow but steady cognitive decline over the last year or two, we haven’t identified any specific factors that appear to be causing this. For instance, the brain scan didn’t show anything different than a normally aged brain. The neuropsychological testing showed memory impairment more than we would expect relative to your age, and the concern is that this may be early Alzheimer’s disease. We can’t say this with certainty and we have to monitor you over time. We are here to work with you, to be a partner with you, to follow you over time. And we can also talk about some of the different treatment options ranging from lifestyle changes—what we call brain healthy lifestyle—to cognitive enhancement medications to clinical trials.”
TCPR: I am going to pretend I’m the patient here. “Does this mean I have dementia and why can’t you tell me for sure?”
Dr. Agronin: I would explain, “The information indicates what we call a neurocognitive disorder and of the different types, it is most consistent with early stage Alzheimer’s disease. The only way to know with 100% certainty is you have to actually look at the brain tissue and obviously we are not going to do that here.”
TCPR: Then the patient might ask, “What does this mean in terms of my future? Does this mean that next year I am not going to be able to do anything?”
Dr. Agronin: I would then say, “Well, if this is Alzheimer’s disease we know that it is a progressive illness. I would liken it to a glacier moving. It is very, very slow; the changes unfold differently for different individuals. We don’t have a cure for it, but there is a tremendous amount we can do to not only lessen the impact of other factors that can worsen it, but there are also some symptomatic treatments we can consider and there are also clinical trials that might offer the hope of slowing down the course of the disease itself.” At this stage of the disease I emphasize with individuals that we are going to work together and we will address every management issue. I don’t get into details about later stages of it because I think that may only worry individuals and I don’t think it is helpful to the discussion. For someone with early stage Alzheimer’s disease, if you can address anxiety and depression in both them and the caregiver, they do better. If you can help them understand the benefits and limitations of a cognitive enhancing regimen, they will be more likely to adhere to it and to maximize its benefits. If you can make certain that their lifestyle is healthy—getting enough exercise, a good diet, having appropriate supervision, not doing dangerous things that are going to cause more problems—they are going to do better in the long run. This is just the tip of the iceberg in terms of management issues so I work with a whole team. I have a neuropsychologist, a social worker, research staff, and support staff to enwrap the patient and their caregivers in a supportive system and I find that everyone does better over time when you take this approach.
If you can make certain that their lifestyle is healthy—getting enough exercise, a good diet, having appropriate supervision, not doing dangerous things that are going to cause more problems—they are going to do better in the long run.
~ Marc Agronin, MD
TCPR: What is your approach to prescribing cognitive enhancers and explaining to patients what they can expect in terms of efficacy?
Dr. Agronin: Well, what I tell patients is that there are a number of cognitive enhancing medications that are approved by the US Food and Drug Administration, but they are not cures. In general, what the data indicate is that people tend to do better on them than off of them so it is worth a trial. We are doing this over the long haul because this is a disease that can go on for a decade or more. I will start one of the acetylcholinesterase inhibitors and I will make sure I maximize the dose because if you don’t, you are simply not getting the benefit from it. Then once they are stabilized and if they are tolerating it, I will add memantine (Namenda). For more on medications, see “Namzaric and Other Cognitive Enhancers for Dementia” on p. 1).
TCPR: How long do you continue using the dementia medications?
Dr. Agronin: There are limited data showing that you get the same benefit with some of the acetylcholinesterase inhibitors over years and not just the several months that most clinical trials look at (Rountree SD et al, Alzheimers Res Ther 2009;1(2):7). In clinical practice, that has been my experience and my impression, so I continue people on them for the duration. I have had a few instances where in later stages when you stop the medication, sometimes you can get declines or changes and that it is hard to get back to their previous baseline if you restart it. You know, arguably, the benefit you get in later stages is quite modest. There are diminishing returns with these medications as you progress in disease because you just have fewer cells that even are producing acetylcholine. If someone is in a terminal phase, it is usually appropriate to withdraw the medication because you might not be seeing any benefit at that point. I take just a very practical approach to it. I want to emphasize that, to me, the use of medications is within the whole context of working with the person and treating them.
TCPR: Thank you, Dr. Agronin.