Communicating With Patients, Families in Evaluations for Alzheimer’s Disease

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In “Beyond Diagnosis: Alzheimer’s Disease,” Cleveland Clinic behavioral neurologist Jagan Pillai, MD, PhD, and host Glenn Campbell discuss how to communicate effectively with patients and families about this life-altering neurodegenerative illness.

Each monthly installment examines an aspect of Alzheimer’s disease care, including making and delivering the diagnosis; shared decision-making about anti-amyloid therapies and other management strategies; providing ongoing support to patients and families; and advising patients on clinical trial participation.

This first of six episodes explores the diagnostic process, including potential reversible causes of cognitive changes and the role of biomarker testing.

The following is a transcript of their remarks:

Campbell: Welcome to “Beyond Diagnosis,” where we talk with doctors about talking with patients. I’m your host, Glenn Campbell. Alzheimer’s disease is a relentless, incurable, and eventually fatal illness that poses profound challenges for patients, families, and clinicians.

Today, we’ll explore how a behavioral neurologist approaches diagnosis, therapy, prognosis, and management of Alzheimer’s many complexities. Our guest is Dr. Jagan Pillai, who directs Cleveland Clinic’s Center for Brain Health. Dr. Pillai, thanks so much for being here.

Pillai: Thank you, Glenn, for having me.

Campbell: A timely and accurate diagnosis is critical. When a patient presents with symptoms of impaired cognition, what process do you use to determine if there’s a neurological basis for it and to differentiate among the various neurodegenerative conditions that could be at play?

Pillai: That’s a great way to start out our conversation because that’s exactly the question a physician or a care provider faces when a patient comes in with a concern for a cognitive change. Is it something I need to escalate to figure out if this is a degenerative condition? Or is it something that I can manage, trying to understand what exactly is driving a reversible cause of cognitive changes?

The best way to look at this is to say that if there is something I can do to improve this person’s condition immediately, I need to do it. So I look for reversible causes. The number one things would be just making sure that medications are not causing cognitive changes. If they’re not having any medical comorbidities — maybe that’s uncontrolled depression or maybe it’s uncontrolled diabetes or other changes like from rheumatological conditions that’s causing significant inflammation in the body.

I mean, all those things can impair cognitive performance, and that’s something that you can address. Less obvious would be things that you need to get from the history of the patient. Like for example, how is their sleep habits? Are they at risk for things like sleep apnea? Are they physically active? Are they taking care of themselves as they’re getting older? And other comorbidities that a person needs to explore, like endocrine abnormalities like thyroid dysfunction or some deficiencies in vitamins.

And these are the first basket of things that I look for because as a physician, if I address them, this person is going to get back to normal and get back to their normal life. Once we have gone through all these reversible causes, and there’s nothing that you can find out and you’re still looking for what else could be causing these things, then you start looking at other patterns that are consistent or concerning for a degenerative condition, and then you work through a plan for that.

Campbell: Because some patients might be unaware of or might downplay their cognitive symptoms, the perspective of close family members is very important, I imagine. How do you manage history taking in light of that? I mean, do you talk to the patient and family together typically?

Pillai: Oftentimes at our center, we encourage patients to come with their family or at least one care provider who knows a little bit about the context of what’s going on, so they can give a third person’s point of view of how all these things are unfolding. Some people are comfortable with that, some patients are not comfortable with that, and that depends on that unique situation of that patient.

So we take into account a patient’s concerns first, if they prefer to have a solo conversation, we go with that. Until there are some clear red flags that we need to talk to the family member, then we let the patient know that this conversation has to happen.

Oftentimes, patients are comfortable having their family member involved in the conversation, so usually it’s much more organic. Sometimes the patient doesn’t want to get an evaluation and maybe the family member is pushing to have an evaluation happen.

I mean, those kinds of things are much more challenging and tricky. We kind of look at an initial conversation with both of them together and try to, again, assess what the context is. And if there are situations like, for example, the patient is delusional or the patient is clearly unaware of the severity of the problem — and we figure out that this is likely neurological where insight cannot be generated with a conversation — in those instances, we might have separate conversations with the family and with the patient.

Campbell: Let’s pivot a little bit and talk a little bit more about the specifics of diagnosis. The FDA approved two biomarker blood tests for Alzheimer’s in 2025. How do these tests figure into your diagnostic workup and what do you tell patients about the tests? For instance, how do you decide who’s an appropriate candidate for testing, when to test, and which test to use?

Pillai: Yeah, that’s a great and timely question. The most dramatic thing in the field that’s been slowly evolving the last 10 years or so, is that we have tests now that can say with very, very high confidence if somebody has Alzheimer’s disease as a potential cause of the cognitive impairment. These tests initially came out, things like PET scans and spinal fluid evaluations that were available in the clinic, but now we have a blood test that’s available that you mentioned that are two different kinds that have been FDA approved.

This has generated a lot of interest, enthusiasm, and awareness among both families, physicians, again, also from the primary care setting, but the field is still struggling how best to implement this thing, how best to make this most impactful. One way to think about that is that this is best used as a screening evaluation to find out if there’s a risk for Alzheimer’s disease, but it’s not yet primetime to use it on anybody with any kind of cognitive concerns.

So there are some specific contexts, it’s more impactful. For instance, to understand the context, you need to understand the time course of the disease itself. When people think of Alzheimer’s disease, they usually think of somebody at later stages of Alzheimer’s disease when they’re not able to take care of themselves, they’re not able to function independently. We use the word dementia for that.

So when we say somebody has Alzheimer’s disease dementia, that means that this person has progressed in Alzheimer’s disease to a point where they’re unable to take care of themselves independently. And before that, there is a stage of mild cognitive impairment of Alzheimer’s disease where a person is functioning independently and still able to take care of their daily routine, but there is a change in their cognition more than expected for their age. But even before the mild cognitive impairment stage, there is a 10- to 15-year duration where there is Alzheimer’s disease changes going on in the background of the brain, but the person is cognitively completely normal.

So we use the word preclinical Alzheimer’s disease. Now, these tests that have become available become positive regardless of what stage you’re in. So there is concern that if you apply this test on somebody without cognitive impairment, it might show a positive result, but that is not helpful to the patient or for the physician to make a clinical therapeutic decision because we don’t know if somebody with preclinical Alzheimer’s disease is going to have symptoms in 2 years, 5 years, 10 years or so.

So the guidelines now are that you need to have a clear cognitive impairment and that’s documented, for more than a year or so. You need to have ruled out the reversible causes of a cognitive impairment, and you really need to consider Alzheimer’s as a high likelihood in this case. If in that specific context, if you get a negative test result, that’s much more clearly saying it’s not Alzheimer’s disease. If it is a positive result, then that needs follow-up testing to confirm it.

Campbell: It sounds like there’s a fine line to walk in many cases. What role does clinical judgment play in properly interpreting the results of the test?

Pillai: Yeah, that’s again, a good question. Like every test, there is a clear negative result, a clear positive result, and there’s this borderline intermediate gray zone. And so patients often like clear answers, “Well, I don’t, I have.” But oftentimes you might also end up in the gray zone, and it becomes a physician’s job to figure out how best to interpret it in the context of things. That’s where getting all the background prep done, getting a clear history, looking for reversible causes, making sure there’s some kind of neuroimaging in place to look for other things that might be going on.

Understanding if this clinical picture is very concerning for Alzheimer’s disease before ordering the test becomes important, because if you have not done the background work, when you get a gray or intermediate result, you are struggling — what to do with it now? And the patient has put up more anxiety and concerns, and the whole purpose of the visit is kind of diluted.

Campbell: You had mentioned PET scans and cerebral spinal fluid testing. Are they still needed to make a definitive Alzheimer’s diagnosis in the context of a positive test?

Pillai: Sometimes patients come with a blood test and ask us to interpret that. So currently, the blood tests are great, but they have some blind spots. For example, if you have some medical comorbidities, that might falsely influence the test’s results, so you might get a false positive in certain situations. The second situation is that you might get a positive blood result when Alzheimer’s disease may be one of the pathologies involved.

So to interpret all these things, we do do additional tests to confirm the primary cause is Alzheimer’s disease using a spinal fluid evaluation or a PET scan or an amyloid PET scan that gives you much more concrete information before starting specific therapies like an anti-amyloid therapy that actually goes in and removes the amyloid from the brain. So you’re right, we do need these additional tests at this point clinically.

Campbell: Thanks for your insights, Dr. Pillai, and thank you for joining us on “Beyond Diagnosis,” where we explore not just what physicians know, but how to effectively and compassionately share that knowledge with patients. See you next time.

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