Leigh Charvet, PhD, & Tehila Eilam-Stock, PhD, on Early Markers of Cognitive Involvement in MS

In this podcast, Dr Charvet and Dr Eilam-Stock discuss the findings from their study, which provided evidence of early neuropsychological markers of cognitive involvement among patients with multiple sclerosis. This study was featured in the 2020 American Academy of Neurology Science Highlights.


Additional Resources:

Eilam-Stock T, Shaw M, Krupp L, Charvet L. Early neuropsychological markets of cognitive involvement in multiple sclerosis. Neurology. 2020;94(15 suppl.).

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Leigh Charvet, PhD, and Tehila Eilam-Stock, PhD, are affiliated with the Department of Neurology at New York University Langone Health.



Christina Vogt: Hello everyone, and welcome back to another podcast. I’m Christina Vogt, associate editor for the Consultant360 Specialty Network. I’m joined by Dr Leigh Charvet and Dr Tehila Eilam-Stock, with the Department of Neurology at NYU Langone Health. Thank you both for joining me today.

Dr Charvet: Thanks for having us.

Dr Eilam-Stock: Thank you.

Christina Vogt: Today, we’ll be discussing their new study, “Early Neuropsychological Markers of Cognitive Involvement in Multiple Sclerosis,” which was published in the journal Neurology. So first, what prompted you and your colleagues to perform this study?

Dr Charvet: This study was funded by the US Department of Defense and completed while we were at Stony Brook Medicine, and the intent of the study was to have imaging markers, as well as very sensitive neuropsychological measures, to really identify those early in the disease at risk for cognitive impairment. Cognitive impairment is a major problem for people living with MS, affecting up to three-fourths of all patients at some point in their disease process. And the idea here is, if we can identify those at greatest risk, we can have interventions that would prevent further decline and preserve quality of life and functioning well in advance of where it would be overt or even noticeable by people early in the disease.

The primary outcome here was a somewhat novel measure called intra-individual variability in response time, and it's a measure of consistency of response. So, we looked at it across reaction time trials. So, somebody does a sustained cognitive task, and we look at the variability of their response times over time. So, not looking at accuracy or even how quick they respond, but that variability, and the hypothesis was that variability was potentially the earliest marker. In doing that, we administered several different types of neuropsych tests and neuropsychological measures, and I'm going to introduce now Dr Eilam-Stock, who has done an analysis of the cognitive measures to see which screening measures might be most sensitive.

Dr Eilam-Stock: Thank you. As Dr Charvet mentioned, we looked at brief cognitive screening measures that are widely used for patients with MS, and we compared them to see which one would be the most sensitive and specific to those early cognitive markers in MS. So, we used the paper-and-pencil test that is called the BICAMS that is widely used in the clinical setting, as well as in research, which includes the single-digit modality test (SDMT), as well as a visual learning and a verbal learning test. We also used the Cogstate, which is a computerized battery, and that includes 3 reaction time tasks and also has been shown to be sensitive to cognitive involvement in MS. And in addition to that, we borrowed a sustained attention task from the research world, the Attention Network Test-Interaction or ANT-I, which looks at the alerting, orienting, and executive control networks of attention and has also been shown to be sensitive to cognitive involvement in MS. And as Dr Charvet mentioned before, we looked into intra-individual variability, or IIV, that we derived across the reaction time tasks–so, across the AMT task, and the Cogstate brief battery tasks. And then, a real strength of the study is that we also included a test of everyday cognitive functioning. We call it the TECA. It was developed in our lab to really look at functioning on tasks that resemble daily tasks. So, things like communication, finance, shopping–how people are really functioning on those daily tasks.

We had 25 participants with MS (with early stages of MS) and 29 matched healthy controls, and when we compared the 3 main measures–the BICAMS, Cogstate brief battery, and IIV–we saw that as expected, all 3 of them significantly differentiated between the groups. So again, that was expected because these are really 3 sensitive measures to cognitive involvement in MS. Next, we looked at the sensitivity and specificity of each of those tests by looking at the receiver operating characteristic curves and the area under the curve, and we found that IIV–that response variability measure–was the most sensitive and specific measure in differentiating between the groups, and that was followed by Cogstate brief battery, the reaction time test. So, that was in accordance to our hypothesis that IIV– the intra-individual variability, the variability in responding–is the most sensitive and specific in that early stage of the disease.

We next also looked at the specificity and sensitivity of the different sub-tests and also of the TECA. And we found that response variability and subtle changes in reaction time, as measured by the IIV and the identification task of the Cogstate brief battery, were the most sensitive and specific to early stages MS. And interestingly, we also found that the TECA, the test of daily functioning, was also highly sensitive and specific to cognitive involvement in these early stages of the disease.

And finally, we wanted to see if we can identify any of these tests and measures as predicting daily functioning. And we conducted an additional analysis that showed that the identification task, the choice reaction time task of the Cogstate brief battery, was the single best predictor of estimated level of daily functioning.

So, to summarize, using these really highly sensitive tests and markers of cognitive involvement, we detected differences between the MS and control groups, even among very young adults and those early in the disease course. The measures that were most sensitive and specific to detection were the identification task, choice reaction time tasks and the IIV measure (the response variability measure), and TECA (the daily functioning measure) showing that slowed and variable processing speed is the hallmark of the earliest changes in cognitive performance in MS.

Christina Vogt: What direction should future research take now after this study?

Dr Charvet: We are very excited for these findings, for the sensitivity of these measures, to really identify people who may be at risk. So, our next steps will be to follow a group with this measure administered early in the disease, maybe at the time of diagnosis, and to really test its predictive value. In addition, we have neuroimaging data so that we're going to link to see if it can be a true marker of underlying disease process, which is really something that we need to better understand the cognitive involvement.

Christina Vogt: And then finally, what are the key takeaways neurologists should keep in mind about this topic?

Dr Eilam-Stock: I think that the take-home message is that using brief computer-based screening measures in the clinic is really easy and critical for identifying those who are at risk for cognitive impairments and in need of treatment. The most effective treatment approach today is cognitive remediation, and we know that prevention of decline in early stages of the disease is more feasible than restoration of functioning once it's impaired. And also, we know that in general, younger individuals early in the disease have better outcomes. So really, identifying and monitoring cognitive changes early in the disease can be critical and really important for treatment planning and care.

Christina Vogt: Thank you both again for joining me today.

Dr Charvet & Dr Eilam-Stock: Thank you.