Andrew E. Budson, MD
Professor of neurology and associate director of the Boston University Alzheimer’s Disease Center. Author, Seven Steps to Managing Your Memory: What’s Normal, What’s Not, and What to Do About It, and Memory Loss, Alzheimer’s Disease, and Dementia: A Practical Guide for Clinicians, 2nd EdDr. Budson has disclosed that he has no relevant financial or other interests in any commercial companies pertaining to this educational activity.
TCPR: The big question for general psychiatrists is how do we go about efficiently assessing memory in a clinical environment that only allows for a 15- to 20-minute visit?
Dr. Budson: If people are actually raising a concern about their memory, that is already something to take seriously. There used to be this rule of thumb that you don’t need to worry about people who are worried about their memory; you need to worry about people who aren’t worried. And that might be true for people with dementia, where there is often a loss of insight. But if you want to pick up memory problems at the earlier, mild cognitive impairment stage, do an evaluation when someone is worried about memory loss.
TCPR: So we should take any memory complaint seriously. What’s the first step in evaluating that?
Dr. Budson: There are three stages of evaluation: first, talking with patients to find out what types of memory problems they are experiencing; second, getting information from caregivers and informants (this can be in the form of questionnaires to save time); and finally, some type of paper-and-pencil testing.
TCPR: That’s a nice memorable way of thinking about it: patient, informants, paper-and-pencil testing. Let’s start with the patient interview.
Dr. Budson: Ask your patient what kind of life impact the memory issue is having. Often, I am trying to tell whether the person has a significant impairment or whether it is consistent with normal aging. In diseases like Alzheimer’s, the hippocampus becomes damaged and cannot hold onto a memory even if it has been learned well. In normal aging, there can be some difficulty in getting information from the memory store in the hippocampus to the frontal lobe for memory retrieval. But at least the hippocampus is still able to hang onto a memory that has been stored well.
TCPR: What sorts of questions should we be asking?
Dr. Budson: I’m typically looking for a situation where the patient’s memory has caused a problem: The patient didn’t show up at the right place or time to meet a friend for lunch, or forgot to pick up the grandkids at soccer. The problem could even involve more mundane things, like remembering a dinner out. While it’s normal for people to forget the name of a restaurant they went to last week, they should not have completely forgotten that they ate out at an Indian restaurant the week before. This is where step 2—talking to people in the patient’s life—might become necessary. You may learn that the patient hasn’t actually made any errors, but things are just requiring much more effort than they used to. The patient is working much harder to keep track of things. In those cases, it can be tricky to distinguish between normal aging and memory impairment.
TCPR: What sort of paper-and-pencil testing do you recommend? Many of us were trained on the Folstein Mini Mental State Examination.
Dr. Budson: My favorite test right now is the MoCA (Montreal Cognitive Assessment). It’s more sensitive than the Mini Mental State Examination, and it is freely available at www.mocatest.org for clinicians to use in their practice.
TCPR: How long does it typically take to administer?
Dr. Budson: Somebody with a normal score will take 8 minutes, and somebody who’s impaired will take around 12 minutes.
TCPR: What would be the typical performance of a person with Alzheimer’s?
Dr. Budson: The typical pattern for Alzheimer’s is patients in their 70s or 80s who show rapid forgetting on the MoCA. By “rapid forgetting,” I’m referring to a specific portion of the test where a person has to read and immediately repeat a list of five words, such as “face,” “velvet,” “church,” “daisy,” and “red.” Five minutes later, the person is asked to recall the words. If the person is not able to recall them freely, even with prompts, that would tell me there’s rapid forgetting present.
TCPR: What diagnostic procedures would you do at that point?
Dr. Budson: I would order a basic dementia workup to rule out reversible causes of cognitive impairment. Screenings typically would include MRI, CBC, electrolytes, thyroid panel, B12, and vitamin D. If it’s Alzheimer’s, on the MRI you’ll see either a normal scan or some atrophy of the hippocampus, anterior temporal lobes, and parietal lobes. If that’s the case and the history is consistent, I would be very comfortable diagnosing Alzheimer’s and starting the patient on a cholinesterase inhibitor without any further workup. However, if the patient does not fit the usual pattern, I might want to get additional neuropsych testing.
TCPR: What other sort of pattern might a patient fall under?
Dr. Budson: For example, let’s say the MoCA testing does not show that the patient has rapid forgetting. Let’s say the patient actually is always able to recall the correct word with cues or multiple choice, but that other parts of the test suggest more of a frontal lobe problem. Or let’s say everything fits the perfect Alzheimer’s pattern, but the person is 55 years old instead of 85 years old. Alzheimer’s disease is unlikely in a 55-year-old, so I would want to do additional testing to make sure I really have the correct diagnosis.
TCPR: Can a psychiatrist feel comfortable making the dementia diagnosis, or should we always at some point be sending our patients to a neurologist to confirm it?
Dr. Budson: A psychiatrist should feel comfortable making the diagnosis in probably upwards of 70% of patients. If you’re seeing patients in their late 70s or 80s who are having memory problems that sound like Alzheimer’s disease, and the scan doesn’t show a large cerebrovascular burden of strokes or any surprises, and the blood tests come back normal, you can rely on your assessment.
TCPR: Let’s talk more about mild cognitive impairment. How does it differ from dementia?
Dr. Budson: Mild cognitive impairment—known in DSM-5 as mild neurocognitive disorder (Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association, 2013)—is distinguished from dementia or major neurocognitive disorder simply based upon whether function is impaired. The word “function” is subjective, but typically it means some type of activity of daily living. I don’t mean just the basic activities of daily living like hygiene and eating, but instrumental activities like being able to go grocery shopping and handling money correctly. What it comes down to is that patients with mild neurocognitive disorder may need to work harder at things, and need help from friends or family from time to time, but they can still live independently.
TCPR: Are the studies basically definitive that if a person has mild cognitive impairment, the condition is going to get worse?
Dr. Budson: Between 50% and 70% of people with mild cognitive impairment do get worse over time. Among those, every year about 15% will develop dementia (Budson AE & O’Connor MK. Seven Steps to Managing Your Memory: What’s Normal, What’s Not, and What to Do About It. New York: Oxford University Press, 2017).
TCPR: That sounds like it could be pretty scary news for a patient. How do you discuss these statistics with someone who has mild cognitive impairment?
Dr. Budson: I usually say, “What the studies show, Mr. Jones, is that the majority of people—somewhere between 50% and 70%—do end up developing some type of dementia like Alzheimer’s, but on the other hand this means that 30% to 50% of people don’t. We’re going to have to wait and see.”
TCPR: Do these patients benefit from cholinesterase inhibitors?
Dr. Budson: They do. A study published by Ron Peterson in 2005 showed that the onset of Alzheimer’s disease could be delayed for a year with medication (Peterson RC et al, N Engl J Med 2005;352(23):2379–2388). However, people should be aware that this is still off-label.
TCPR: Since we’re on the subject of cholinesterase inhibitors, how would you characterize their effectiveness in dementia? There’s some uncertainty regarding their efficacy.
Dr. Budson: The studies show that the effect of the cholinesterase inhibitors is equivalent to turning back the clock on people’s memory problems by 6 to 12 months—but then the clock starts ticking down again, and a person’s memory will decline along approximately the same slope that it did before. When I talk to patients about this, I actually draw the curves. If I don’t, people get the wrong impression that somehow their memories are going to be stabilized. And then, when their memory starts dropping below baseline, below where it was on the first day that I saw them, they assume that the medication is no longer working and want to stop it. But then their memory drops 6 to 12 months of function in 1 to 2 weeks.
TCPR: Can they get that back?
Dr. Budson: Study after study has shown that if they stop the medication and then restart it, they don’t get all the way back up to where they would be if they had continued their treatment without interruption.
TCPR: Can you describe your approach to prescribing cholinesterase inhibitors?
Dr. Budson: I will start with either donepezil or extended-release galantamine. For donepezil, I usually start with 5 mg daily for a month, then I go up to 10 mg and will stay at that dose if the patient is doing well. Later, if the patient is continuing to worsen, I will try to push the dose up to 15 mg or 20 mg. I say “try” because I’m often limited by side effects such as gastrointestinal issues and, occasionally, vivid dreams at night. I feel equally comfortable about starting with sustained-release galantamine. I’ll start at 8 mg once in the morning, and then after a month I’ll increase that once-a-day dose to 16 mg. The 16 mg dose of sustained-release galantamine is equivalent to 10 mg of donepezil, and you can go up to 24 mg of galantamine if needed. If the patient is bothered by vivid dreams, I will switch to immediate-release galantamine and start with 4 mg in the morning. After a month, if the patient has been doing well and has not been having any problems, I might try 8 mg.
TCPR: Do you ever prescribe the rivastigmine patch?
Dr. Budson: Sometimes—mainly for patients who are having intolerable GI side effects. The patch causes fewer GI side effects than other formulations, but it’s more expensive than pills, and it’s also a little bit more cumbersome because you really need another person to take it off or put it on. It comes in a 4.6 mg per 24-hour patch, a 9.5 mg per 24-hour patch, and a 13.3 mg per 24-hour patch. In general, I will start people on the 4.6 mg/24-hour patch and then move them up to the 9.5 mg. I rarely put people on the 13.3 mg, because that tends to cause the GI side effects that I’m using the patch to avoid.
TCPR: What about memantine?
Dr. Budson: Memantine, which is FDA-approved for moderate to severe Alzheimer’s, has been shown to help patients in terms of their attention, alertness, and initiative; it decreases apathy. The main side effects are drowsiness and confusion. Interestingly, memantine’s side effects are worse in patients with milder disease. I learned this the hard way—I saw that many of my mild patients would end up with drowsiness or confusion. I think the problem is that if you give people extra dopamine when their levels are already normal, you are just going to push them over and cause either drowsiness or confusion.
TCPR: When is it time to start a patient on memantine?
Dr. Budson: Moderate to severe dementia by definition means an MMSE score of 15 or lower, or a MoCA score of 10 or lower. Those are the trigger points. I’m a big believer in combination therapy—memantine plus cholinesterase inhibitor—when a patient gets to that stage.