NeuroVoices: Dejan Jakimovski, MD, PhD, on Identifying a Relationship in MS Between Brain Structures and Cognitive Performance

Dejan Jakimovski, MD, PhD

Multiple sclerosis (MS) has typically been thought of as a disease that presents in the young and working population; however, recent claims data has shown that the highest prevalence of patients with MS is in women and men aged 55-64 years (24%), followed by 65-74 years (13%). To date, there has been little uncovered about neurodegenerative brain changes in MS and their link with cognitive performance in elders with the disease. New research led by Dejan Jakimovski, MD, PhD, will aim to understand the most clinically relevant brain regions that cause cognitive decline, and thus be able to, hopefully, predict an individual’s risk for that cognitive decline.

A recently awarded pilot research grant by the Consortium of Multiple Sclerosis Centers (CMSC) will fuel Jakimovski’s new study, which analyzes the anatomical features of decline and their relationship with different cognitive domains. The research aims to not only determine these correlations but compare the structure–cognition relationships within elderly patients with MS above the age of 50 years with previously published data regarding young patients with MS between the ages of 20 and 50 years.

Jakimovski, research assistant professor, Buffalo Neuroimaging Analysis Center, recently sat down with NeurologyLive® for a new iteration of NeuroVoices to discuss the grant and all that it entails. He detailed the data previously established to this point on cognition and MS, the challenges in detecting cognitive decline as well as whether the current methods used for detection are up to standard.

NeurologyLive®: What previous work led to this research?

Dejan Jakimovski, MD, PhD: The background of cognitive decline in multiple sclerosis has been mostly focused on cognitive processing speed. That association has been shown to be with deep gray matter structures like the thalamus, which is the focal point of pathology in multiple sclerosis and is deeply connected with speed of processing information. This cognitive impairment that these patients have generally is prevalent in all spheres of our population, including young and old patients with MS. However, in the past several years, we have looked into more cognitive domains in MS and examining cognitive domains in both young and old patients with early MS.

What we initially saw, was in addition to the cognitive processing speed impairment, which is already established in the literature, we saw an increase in verbal fluency deficits, especially specifically found in our aging population. We thought that this verbal fluency deficit, specifically categorical verbal fluency, is something that might be specific to our aging population. We wanted to better classify what are the structures and what is driving this verbal, generative fluency impairment that we don’t really see in our younger MS population.

The idea of pursuing this is 2-fold. One, you understand that there’s a different cognitive domain that is impaired in the aging population and that maybe we can better target it with some rehabilitative techniques. Second, this cognitive domain is sometimes impaired in more traditional neurodegenerative diseases of older individuals. We wanted to see how we can differentiate verbal deficits or verbal fluency deficits between aging patients with multiple sclerosis, compared to someone who might be at an age where a new onset of Alzheimer disease or vascular dementia is also a risk factor in these patients.

How will your grant from CMSC be used?

Based on this data, we aim to understand what the structural drivers of verbal fluency deficits are. This is where the CMSC grant comes into play, where we were given a small pilot amount of funds to retrospectively look at 100 aging patients with MS that have certain verbal fluency deficits, and determine what structures, particularly cortical or gray matter, are driving this impairment.

What do we currently know about how MS affects cognitive performance?

We did see that this verbal fluency is not typically seen in our younger MS population. In our study, we investigated patients that are 50 years or older, with an average age around 64 years. This population demonstrated that up to 50% of these people have verbal, generative fluency impairments, which we do not see in our young population. We wanted to understand why that’s the case. Why are certain cognitive domains affected in our young population, and other cognitive domains seen in our older population? Based on which cognitive domains are being affected, that will drive the clinical management of the cognitive impairments. We cannot use the same techniques of learning and teaching these patients how to deal with their cognitive impairment, because if they have speech impairment vs verbal fluency impairment, those are 2 different cognitive concepts and domains.

Are there challenges in detecting the amount of cognitive loss? Which tools seem the most useful for that?

The typical battery that we use clinically and in the research world to determine cognitive impairment is called BICAMS, which stands for Brief International Cognitive Assessment of Multiple Sclerosis. It consists of 3 specific tests that test processing speed in both verbal and visual spatial memory. Based on this, these tests do not cover measurements of verbal fluency and are not able to detect verbal fluency impairment. This is where we add another test called COVAT, or Controlled Oral Verbal Word Association Test. In this test, we ask participants to provide us with as many words as possible that starts on a certain letter of the alphabet within a certain amount of time. For example, I will ask the patient, can you please tell me as many words as you can think starting with the letter R. I just write down how many words they can come up with in 60 seconds. That’s the verbal fluency part, which we split into categorical verbal fluency, where we say, “can you provide us as many words as you can in the category of animals?” And it can start on any letter of the alphabet.

What we see is that our aging MS population definitely has lower amount of words given to us in those 60 seconds. If we see approximately 15-20 words given by our young MS population and healthy controls, whereas in our aging MS population, they give us between 10 words or something like that. In the categorical verbal fluency, they lack even more, and there’s an even bigger difference there. Patients will give me 10 or 15 animals within 60 seconds, whereas the healthy control of their age group will give me 40 to 50 animals within 60 seconds. That’s our main test, that we determine what is the verbal fluency performance in these patients and if there’s an impairment in them.

Do you believe there is a need for improved methods of detecting this cognitive decline?

I think that BICAMS, what is currently the standard for determining cognitive impairment, is sufficient enough for the general MS population, but we might want to supplement it with this one additional test of verbal fluency to our aging population. The batteries should be based on the age of our patients. If we have a patient who is 50, 60, 70 years old with multiple sclerosis, I would add on this test, which is only a 60-second type of test. It will not take more than several minutes to our additional battery. We can see if an addition to the previously known processing speed impairments, our patients will have this generative verbal fluency type of impairment as well.

Has the literature pointed to specific types of MS that experience worsened cognitive function?

In congruence with our report, several other reports showed the verbal fluency impairment in the literature. If we go back to the neurodegenerative pathway, we see the literature very well agrees that the deep gray matter structures like the thalamus happen early in the disease. This is affecting their processing speed in our patients with MS, our young patients with MS too. As the disease progresses after 15-20 years, or through transitions into this so-called secondary progressive MS, we can see that the neurodegeneration or the actual atrophy of the brain, the pathology of the brain, shifts, from the deep gray matter structures of the thalamus to a greater atrophy or greater pathology in the surface cortical regions.

That’s how this grant from CMSC comes into play. We’re trying to see, which cortical structures are driving the verbal fluency, this new impairment that comes in our aging patients? If so, is the thalamus the one driving this in our young population or is it a structure that’s being damaged early in the disease? And now different structures later in the disease are being damaged later in the disease that might drive this impairment.

Transcript edited for clarity. For more iterations of NeuroVoices, click here.

REFERENCE

Seeking the relationship between brains structure and cognitive performance in elderly people with MS. News release. Buffalo Neuroimaging Analysis Center. October 29, 2021. Accessed December 21, 2021. https://www.bnac.net/news/seeking-the-relationship-between-brain-structure-and-cognitive-performance-in-elderly-people-with-ms