Initiating and Monitoring Therapy in Alzheimer Disease

Alireza Atri, MD, PhD: I’ll turn to Brad. Brad, what are some of the patient factors when you consider deciding how to start therapy? How do you monitor it? And again, talk about the expectations you give people about the medicines.

Bradford C. Dickerson, MD: Sure. I think for the cholinesterase inhibitors, they’re efficacious and they’ve been demonstrated to be efficacious, as Marc said, in patients with mild dementia due to Alzheimer disease. There’s also efficacy data in patients with Lewy body dementia. I think some of the best responders to these medications are often people with Lewy body dementia. There have been other smaller studies that suggest that they might be helpful with vascular dementia or with other pathologies that lead to memory impairment, including multiple sclerosis and traumatic brain injury.

There are a variety of patient populations that could benefit. In general, there haven’t been data to show that they’ve been effective in patients with mild cognitive impairment, even if it’s thought to be caused by Alzheimer disease. Those studies have not really been conducted in a focused, modern way. We often see off-label use of these medications in patients with amnesic mild cognitive impairment, in particular. And I think there’s anecdotal evidence that they benefit those patients.

It’s always important, continuing along the discussion of diagnostic disclosure that Mary mentioned, to try to understand what the patients’ and families’ interests in medications are and what their experiences with medications are. It’s often the case that when we explain that these medications do have adverse effects—like any medications—but that for the most part, they are quite manageable, that a trial of a cholinesterase inhibitor in a patient with mild Alzheimer dementia is met well from the perspective of the patient and family member.

There’s often the hope that they can do things beyond what we believe they’re going to be able to do. It’s always important to set the expectation that not everybody even has a noticeable response in their daily lives to these medications. And even if they do, they don’t, as Marc said, affect disease progression in a way that would suggest slowing of the disease process. So I often draw a curve that shows progression. For instance, if you don’t treat it, it’s a parallel curve that is up a little to show that you might get a little bit of a boost in your memory or other cognitive abilities, but that the rate of progression is going to likely remain mostly, largely, the same. And then later on, if you add memantine, you might get a similar boost. But again, the rate of progression, overall, will be the same; maybe you would maintain function above where you would have been if you weren’t taking this combination therapy as you’ve shown with some of your own data.

Setting those expectations is important, and often with a graphical support, to really drive that fact home—that the progression is going to still happen. We may see some benefit, but even if we don’t, just because the patient is declining doesn’t mean the medicine is not working. And I think that can be a hard thing to judge. Sometimes what we see is that if people—the clinician and the patient and care partner—have been on donepezil or another cholinesterase inhibitor for a year and they’re worse off, everybody kind of feels like, “Is this really even doing anything?” You might do a trial off it, and the patient is clearly worse than they were when they were on it. So that can be 1 way to make a judgment.

A lot of times if the patient is tolerating the medication well, we just hope that it’s working and continue it. I think some patients don’t tolerate these medications well. They have substantial gastrointestinal adverse effects that are persistent and that can be challenging. Often trying 1 of the other cholinesterase inhibitor oral medications is the easiest way to go; and seeing if they might be able to tolerate 1 of the other medications in the same class. There are also transdermal formulations that can be tried as well, if the person is particularly sensitive to gastrointestinal adverse effects.

Those are some of the things that I look at in my consideration. When a patient clearly has a non-Alzheimer form of dementia such as frontotemporal degeneration, these medications don’t help. In terms of the AD [Alzheimer disease] medications, they sometimes can even sort of activate patients in ways that leads to more disruptive behavioral symptoms.

It’s important to talk about the standard approved medications. It’s also important to talk about the symptoms we can treat with other kinds of medications, that are often very helpful in dealing with some of the symptoms that Marc has been talking about in relation to mood-related symptoms—potentially psychosis, which can be so devastating for families to deal with. Considering those medications, including ones with efficacy data or sometimes just off-label use, is important to discuss with patients and families.

Transcript edited for clarity.