In Alzheimer, Precision of Phrasing is Paramount

Marwan Sabbagh, MD, Director Lou Ruvo Center for Brain Health, Cleveland Clinic

Marwan Sabbagh, MD

With multiple advancements for Alzheimer disease making their way through the early stages of clinical development, the excitement around treatment has never been greater.

For Marwan Sabbagh, MD, director, Cleveland Clinic Lou Ruvo Center for Brain Health, that excitement is different than previous iterations. In a field that has seen hundreds of failed trials and therapies, cautious optimism is the usual. But Sabbagh has a belief that many in the dementia space are seemingly beginning to share: that this disease could soon be manageable.

With that potential on the near horizon, Sabbagh told NeurologyLive that the clarification about the cause of a patient’s dementia is becoming more critical. Physicians need to know not just that there is dementia, but what state the dementia is in and its etiology. Sabbagh provided insight into this, among other topics, in an interview.

NeurologyLive: How important is to identify and treat these neuropsychiatric symptoms?

Marwan Sabbagh, MD: It’s a big deal. When we really talk about the dementia state now, we draw down on staging it as mild, moderate, and severe, and we start to see the emergence of the neuropsychiatric features in the late mild, early moderate stage. Oftentimes they can eclipse the entire disease. After a while, patients and their families don’t care about the forgetfulness, they care about the wandering, the paranoia, the delusion, the agitation, the trouble sleeping, and that really starts to take over the disease. It becomes a huge amount of the burden of the disease.

While we know that we use off-label drugs, there are no clear consensus guidelines and we’re winging it when it comes to managing neuropsychiatric features. There are several drugs being developed for behavioral symptoms and those are actually very, very close to being approved. I suspect we’ll see more drugs approved to treat behavioral symptoms within a year or 2. That is a huge area of unmet need and I suspect we’ll see some drugs to fill the gap.

How important is it to detect the disease early?

Very. There are the new ATN criteria, amyloid, tau, neurodegeneration criteria, which is redefining—and this came out this year, in 2018—but the ATN criteria recasts the disease from a clinical construct to a pathological construct. This has not been applied clinically, but it will kind of evolve. The reason this is important is we know that pathological changes precede the onset of symptoms by up to 20 years, and, in fact, amyloid can be detected as early as 20 years before the onset of symptoms, according to the DIAN study (the Dominantly Inherited Alzheimer Network observational study). DIAN has shown clearly that they can detect changes in the brain decades before the onset of symptoms. The point is there’s now a push to detect the disease with or without symptoms.

The reason I say this is that people mix terms together, and precision is becoming paramount in how we discuss things. We no longer say Alzheimer disease, we would say dementia due to Alzheimer, or due to Parkinson’s, Lewy Bodies, etc.

So, the state would be dementia, meaning clinical cognitive decline associated with functional impairment—that’s dementia—and we would talk about that followed by the etiology. Then with mild cognitive impairment, again, it’s the state followed by the etiology. Impairment due to Alzheimer etc. Then we would talk about a pre-clinical state of Alzheimer disease. All of it is Alzheimer, whether you have symptoms or you’re fully demented. All of it is Alzheimer, but we’re starting to talk about Alzheimer in the different states as one disease in different states, and that’s why the ATN data is going to be so important moving forward.

Can you speak to the misconceptions you’ve identified in the space?

The first common misconception was the definition that I just talked about, conflating disease with the disease state. People use the terms interchangeably. It’s important that we define the state—meaning normal, mild cognitive impairment, dementia—and then etiology. That’s misconception number 1.

Misconception number 2 is that you can only diagnose Alzheimer disease with an autopsy. That was what was put forth in 1984 using NINCDS-ADRDA criteria. I am here to tell you that our clinical and specialty centers like mine and other centers around the country, we have precision rates north of 90% accuracy with the use of PET, CSF, genetic markers, other biomarkers. We are very much further along in using advanced diagnostics to diagnose Alzheimer with great confidence.

Then, misconception number 3 is the field is still mired in this large veil of futility. That “there’s no point, so why bother?” We are so much closer than people think to changing the trajectory of this disease. We are so much closer to making this from a terminal disease to a chronic disease. This is the diabetes of our time. This is the HIV of our time. We will do it, not a generation from now, but fairly soon. Not cure it, don’t get me wrong that’s not what I want to say—but manage it. You’ll come in, we’ll do some diagnostic tests, we’ll diagnose the Alzheimer, we’ll put you on a treatment plan, which will probably be a combination of 3 to 5 drugs and then you’ll stabilize, and that’s what’s going to happen fairly soon I suspect.

What’s the best advice you can give to clinicians that are treating and managing and diagnosing this disease?

My best advice is that the field is changing. It’s important to be well informed because your patients, if they don’t go to you, they’re going to Dr. Google, so it’s important to stay well informed, it’s a very rapidly changing field. The second thing is to have your patients be engaged. We’ll never get the answers to these important questions that we talked about without patient and participant engagement. That kind of engagement starts at the physician level.

Transcript edited for clarity.