Current Series: Advances Treatment Alzheimers Disease

Jeffrey L. Cummings, MD, ScD: Let’s go on to the next question, Elaine. I’m going to ask you to tell us, what are the signs and symptoms that would prompt a clinician to suspect Alzheimer disease [AD]? Because most of these patients will most likely be in the MCI [mild cognitive impairment]-to-mild-AD phase, it’s not an obvious presentation. What’s the value, and how do you approach it?

Elaine R. Peskind, MD: Well, the domains of thinking functions or cognition that are most affected early on are memory and executive functions. Executive function is really to plan in sequencing and carry out a complex task.

With respect to memory, often the earliest signs and symptoms are being repetitive in conversation, being forgetful of recent events, and not remembering so well to take your medications or how to organize your medications. Sometimes it’s not paying the bills on time. Or if a person was doing the taxes year after year, and this year they can’t do the taxes. And then Richard brought up word-finding difficulty, and often at this stage word-finding difficulty may become apparent in your examination of the patient, in which you find the person is slowing down their conversation. They have a blank space where they’re trying to think of the word, and you find yourself providing the word. That should be a clue to you.

In the primary care setting, the person has diabetes or has hypertension, and you think your care is providing what should manage these conditions well, but still there’s not good control. And you should suspect that maybe the person is not taking their medications, maybe not remembering to take their medications.

Jeffrey L. Cummings, MD, ScD: Yes, those are great signs. One of the things that I recently had a discussion around was when I saw a 56-year-old with Alzheimer disease, amyloid-positive scanning. And his main complaint was slowness, that he simply couldn’t accomplish things that he was used to accomplishing in his employment at the same rate that he could before. It wasn’t specifically memory, and I wondered whether that was maybe a little more characteristic of the early onset disease. They’re in the employment environment, they’re having a different set of demands on them, and slowness was the primary complaint. Anybody else heard that or seen that in young patients?

Alireza Atri, MD, PhD: A big part of my practice is actually seeing people who have early onset changes. And I would say typically atypical presentations are typical. It’s not all memory all the time. I think mental efficiency changes and early changes in mood and sleep as individuals actually work harder and harder to compensate in a work environment and multiple challenges in their life, those things become apparent a lot earlier to other folks. Sometimes it’s not just memory, so it’s that mental efficiency that goes down.

Jeffrey L. Cummings, MD, ScD: Very good. Marwan, you look like you want to comment.

Marwan Sabbagh, MD: Recently, I was told about something called the head-turning sign. I started looking for it, and I find it to be pretty common. The head-turning sign is when you ask the patient something, and they’ll answer and then turn to their next of kin to confirm it.

Jeffrey L. Cummings, MD, ScD: To confirm it, right. Yes.

Marwan Sabbagh, MD: Actually, I’ve started documenting it in my medical record.

Jeffrey L. Cummings, MD, ScD: I’m sure we’ve all seen that, even in more advanced cases. “How old are you?” And there’s the head-turning sign.

Richard Isaacson, MD: That’s exactly right.

Jeffrey L. Cummings, MD, ScD: If there’s a little uncertainty about how old you are.

Marwan Sabbagh, MD: That brings up the point that part of the evaluation is a careful examination, and I’m not talking physical or neurological. I’m just observing the patient—how they think, their fluency, their language, and their thought content. Just observation is a really important part of the evaluation.

Jeffrey L. Cummings, MD, ScD: Marwan, I want to direct the next question to you. Are most cases of Alzheimer disease diagnosed in primary care or by a neurologist? And continuing in that, how can the primary care doctor and the neurologist work together?

Marwan Sabbagh, MD: It’s a really important question, Jeff, because I’m seeing that it’s a big problem. We’re noticing in our own clinic, the Cleveland Clinic, that 80% of referring diagnoses are not the diagnoses we end up entering in the medical record. Physicians do not feel comfortable making a diagnosis of Alzheimer dementia. They’re still stuck on B12, TSH [thyroid-stimulating hormone], and MRI [magnetic resonance imaging tests]. And they think, “Well, they’re normal, so I don’t know what this is,” so they’ll code it as cognitive change. Physicians—primary care physicians in particular, who we expect to make the diagnosis—can’t. In the best-case scenario, the data suggest it’s accurate somewhere around 66% of the time. So we know that a clinical diagnosis beyond the superspecialist is not accurate. It’s correct only 2 of 3 times. So 1 thing we can say is that we’re trying to push primary care physicians to be more comfortable with making the diagnosis. But at least they should say there’s an issue and that they should refer.

Jeffrey L. Cummings, MD, ScD: And how do other people see this?

Alireza Atri, MD, PhD: Well, I agree with Marwan. I think this is an obstacle that is surmountable, though. I think typical presentations of Alzheimer disease are mixed conditions. Because I think what we’re learning is that as people get into their late 70s and 80s and beyond, the rule is having at least 2 or 3 different brain changes, including Alzheimer, vascular skin with brain injury, and other conditions like it. I think that with enough support and knowledge, primary care clinicians can actually diagnose typical cases well enough to initiate treatments. When there are questions about atypical symptoms—rapid progression, early onset—I think with those conditions, if there’s a moving component, those folks really need to be on a fast path to be referred to someone else.

Jeffrey L. Cummings, MD, ScD: This question implies that there should be more of a partnership between primary care physicians and neurologists. I think maybe we haven’t done the best job of that. It’s difficult, of course, because we’re all in health care systems, and we don’t have control of these relationships. But we should struggle more with it, because I think the primary care physician often would benefit by more expert input, and we would benefit from being able to relate more to the primary care physicians and have patients referred more often for clinical trials or for appropriate therapies. I think that’s a goal for all of us.

Elaine R. Peskind, MD: I think, though, that making the diagnosis of a typical presentation of Alzheimer disease is not difficult. But I think there is a bit of a problem in your usual primary care practice where appointments are scheduled every 15 or 20 minutes. And the primary care provider is dealing with a whole list of other problems and literally doesn’t have the time to take that careful history. And if you make the diagnosis, this is a devastating diagnosis. You have to have time to deal with all the fallout from that.

Jeffrey L. Cummings, MD, ScD: It’s a great point, and that’s another reason I think we need to help our primary care colleagues.

Alireza Atri, MD, PhD: I want to make a quick point about that. I think that’s really true. I think what we need to do is actually allow our colleagues to appreciate that they don’t have time not to make the diagnosis in the sense that they’re dealing with individuals in their 70s and 80s, and we know that the rate of impairment or dementia is upward of 25% to 40% in that group. If they’re dealing with their own medications, with diabetes medications, blood pressure medications, or other things like that, that’s dangerous. And so a lot of hospitalizations and ED [emergency department] visits are actually because with individuals, their medical condition hasn’t changed, but their ability to manage it has changed. Unrecognized impairment is really costly for time, etc, for primary care clinicians. So if they were to take the time to focus on that during the annual wellness visit or other things, or bringing people back and identifying these folks as having a complex medical condition, I think their practice would actually save time and money.

Elaine R. Peskind, MD: I absolutely agree with you, but I’ve had even very senior primary care physicians say to me, “Well, I didn’t know. I just know that I need to remind them again to take their medications.” And then what good is that going to do when as soon as they walk out the door, they’re going to forget it.

Alireza Atri, MD, PhD: I want to add that we put the onus on primary care physicians to make a diagnosis, but they get almost no training in their residency about this. I think it’s not an accurate way to go about doing this. What we really want to do is make sure they detect a change and are willing to refer. I think if we could get that, that’s our first step. But saying that they can make a diagnosis has not been shown to be very accurate.

Jeffrey L. Cummings, MD, ScD: Good point.