Imad Najm, MD, on the World Brain Study After 1 Year

Imad Najm, MD

At the 2023 American Academy of Neurology (AAN) Annual Meeting, April 22-27, in Boston, Massachusetts, Imad Najm, MD, the director of Cleveland Clinic's Epilepsy Center at the Cleveland Clinic Neurological Institute, in Ohio, presented some of the early findings from the World Brain Study—a major undertaking being conducted out of Cleveland Clinic.

The study is seeking to provide additional information for improving the time to diagnosis and treatment for patients with neurologic disease. Understanding the underlying changes occurring in these conditions remains a significant challenge for those in the field. Often, years before symptoms arise, a “silent phase” occurs where changes happen in the brain that, in some cases, may put patients at risk for a number of neurologic conditions.

Introduced in early 2022, Cleveland Clinic’s Brain Study will collect data from up to 200,000 neurologically healthy participants on a yearly basis for up to 20 years. The cohort consists of those aged 50 years and older with no neurological disorder and neurologically healthy adults aged 20 years and older who have a first-degree relative diagnosed with multiple sclerosis. Led by Najm, the study will use serial assessments that include a neurological exam, quality-of-life questionnaires, blood and stool sampling, echocardiogram, electrocardiogram, and MRI, among others.

To find out more about what has been suggested thus far, NeurologyLive^® caught up with Najm at AAN 2023. He shared insight into the most recent data that have been compiled now 1 year into the study, how it aligns with current knowledge and estimates, and how it will inform the future of the evaluation.

NeurologyLive: You are here to talk about the World Brain Study, which was initiated early last year—can you summarize what you're presenting here at AAN?

Imad Najm, MD: Yes, we started it on January 17, 2022. It's been now almost 15 months, and what I'm going to be presenting today is a very fast overview of why we did the study, how the study is structured, and where we are now. To summarize, we're taking a look at what happened in the brain and in the body. You are in what we call the silent phase, which is the phase that precedes by 1, 5, 10, or 15 years, the first expression of any clinical sign or symptom of one of the neurodegenerative diseases of older ages. For example, looking at patients or volunteers who develop Alzheimer disease, and being able to go into this bank and see what happened. What did we miss? Or what did we see that we did not pay too much attention to that, “Oh, this would be a potential biomarker for this disease.” This will be done through yearly visits and a very detailed assessment of multiple functions of the brain and other organs in the body. And, in addition, we are taking some biological samples to further study later on.

Now, I'm going to be giving an update on what's happened for the last 15 months, and actually, as of last Friday, April 21, we had 975 volunteers who were enrolled—meaning they were examined, and they got to have the full first year of examination and all of the studies were fulfilled. I'll be talking about what did we learn about these 975—actually, we analyzed 990, but 975 from the last two weeks—and then here I will share with them some of the current findings. The median age is around 65 years for our group. I’ll be talking about the gender splits—actually, interestingly enough, we have 75% females and 25% males—and then looking at the racial and ethnic mix of this. And we still have this as a challenging thing—we have almost 90% white individuals, and the rest are African American, Hispanic, Asian, or Native American. So, this is an area of challenge that we are trying to remedy to through community outreach. As part of our plans, we're going to be expanding the study down to Florida, where we'll have much more of the Latino/Hispanic population coverage and some Native American individuals as well.

Then, we'll talk a little bit about the general characteristics of these individuals. For example, looking at their cognitive function, we have a small number of them that do have some cognitive problems—like 9 or 10, out of the 900. It's a very tiny percentage, which is by design because you're looking at individuals who are, quote, unquote, healthy. Then, we'll look at the incidence of mental health disorders. It's almost 50% of these individuals reported or showed during the surveys, signs of either depression or anxiety. Very rarely, we have some schizophrenia, but a significant number of the respondents, so far, have a current history of depression or anxiety.

Then, we're looking at the cardiovascular. Almost one-third of them have some cardiovascular problems. That includes abnormalities on the electrocardiogram, or they may have some history of heart attacks in the past, or high blood pressure, which we know is not uncommon. And then some of them, also, they think they came in as healthy—neurologically healthy, we would not eliminate any patient or any person with a history of a nonbrain problem—but they do have some issues. They have weaknesses, gait problems, and essential tremor, which we know is very prevalent. The older we get, the more we're going to have tremor.

I will also share what we learned about, for example, quality of life and what would be the potential factors that would impact the quality of life. Actually, the biggest, the most impactful factor, is sleep problems. Sleep problems were the most impactful thing in determining how good or not optimal the quality of life was. This is in brief, what I'm going to be presenting today.

How are these findings aligning with what the existing literature and research have suggested?

Well, for example, we're looking at incidents of MRI abnormalities. When you're looking at MRI abnormalities, we look at abnormalities of the white matter, these white spots, the bright spots, that we see, which are quite common. But although the majority of them are very minimal or minor, we have some of what we call incidental findings on the MRI—aneurysms, for example. Brain aneurysm was shown in 19 out of the 909. Thankfully, many of them are smaller. We have around 10 to 15 individuals who had tumors that didn't know about. Thankfully, these tumors mainly were meningiomas, and a couple of them had throat tumors outside the brain. But we do scan it, and we've seen this. Some of them have small bleeds, like subdural hematomas. What we found so far is almost exactly what was published in the journal Healthy Population.

What has been shown thus far regarding the development of the various neurological diseases this study is seeking to reveal?

We looked at if we found anything that could be a risk factor for the development of some of the diseases. For example, in patients with multiple sclerosis, they do have, on MRI, some white matter problems that are very characteristic of multiple sclerosis. In those individuals who are first-degree relatives of a patient with MS, we found in 9 of them some changes on the MRI, that could be the beginning of MS in them. So that is intriguing to say the least. For patients, for example, with potential dementia, we are seeing around 10 individuals who have some issues with memory. Is it the beginning, or it is MCI? We do not yet know. For stroke, we're seeing around 20 of these individuals, they had some strokes that we see on the MRI they didn't know about, or some more white matter changes that may be suggestive of a vascular problem. Then, on the EEG, we have I think 11 volunteers, where you're seeing epileptic activities on them—which, by the way, isn't that different than their 1.2% rate that was published 50 years ago now.

In a way, we have been comforted by the fact that they look, for the most part, except in the racial and ethnic position, like what is described in the literature. We're looking at, for example, the incidence of COVID, which is exactly what was published. About 50% have a history of COVID. We're looking at smoking history. Our group shows less incidence of smoking than historically what is published at the national level. For alcohol use, our group has shown less alcohol use than the general population—could it be because they don't want to say it, or it could be that it's different? We’ll keep paying attention here. The main reason we're looking at all of these things is to make sure our study is representative of our society. And these numbers here that I shared with you, give us a lot of information on where to focus next.

Transcript edited for clarity. Click here for more coverage on AAN 2023.