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NeuroVoices: Dejan Jakimovski, MD, PhD, on the Need to Address Cognitive Decline in an Aging MS Population

SAP Partner | <b>Buffalo Neuroimaging Analysis Center</b>

The research assistant professor at the Buffalo Neuroimaging Analysis Center discussed the importance of continued research on how patients with multiple sclerosis experience cognitive decline as they age.

This is a 2-part interview. To view part 1, click here.

Once thought of as a disease that was typically present in a younger population, more people with multiple sclerosis (MS) are continuing to live into their elder years because of the advancements in disease-modifying therapies and improvements in quality of life. As these patients continue to age, though, they begin cognitively decline. Currently, it is unclear whether this is fully attributable to MS processes, or the presence of another underlying condition, like Alzheimer disease.

New research led by Dejan Jakimovski, MD, PhD, research assistant professor, Buffalo Neuroimaging Analysis Center, aims to determine which brain structures are responsible for specific types of cognitive decline. Funded by a pilot research grant from the Consortium of Multiple Sclerosis Centers, he and his colleagues will analyze anatomical features of decline, including certain gray matter structures, and their relationship with different cognitive domains in a cohort of 100 aging patients with MS.

Jakimovski expressed the need for a more concerted effort toward understanding the epidemiology of the aging MS population, being that there are growing numbers of elderly patients in the clinic setting. In a new iteration of NeuroVoices, he broke down the areas of research clinicians should focus on, whether cognitive prevention is feasible for these patients, and the challenges in differentiating how much cognitive decline is related to MS.

NeurologyLive®: What are your thoughts on cognitive prevention approaches? Are there any that come to mind?

Dejan Jakimovski, MD, PhD: In terms of preventive techniques we can use, verbal fluency deficits are something that a lot of clinicians will see in their patients with MS, but they have not been personally quantified before. A lot of patients with MS will say, “I know the word, it’s on the tip of my tongue, it just doesn’t come out. I cannot pronounce it; I cannot say it.” Maybe allowing our patients with MS to have more time to come up with their wording will help their lifestyle, their work conditions. If we try to find out how we can help improve the work conditions for patients with MS and minimize these so-called “negative work events”—this means they’re not getting the promotion, getting less salary, or are being cited for having a low performance—maybe, by understanding that these patients have specific impairments where they need more time to verbalize their thoughts, it will prevent them from losing their job or going on disability moving forward. First, we need to understand what pathologies are happening cognitively in our later stages of multiple sclerosis before we develop a targeted type of cognitive rehabilitation for them specifically.

What aspects of research should clinicians focus on to get more answers?

Epidemiologically, the MS population is drastically changing due to the big changes that are happening within the space in terms of treatment, better quality of life, et cetera. The average age of a patient with MS in 1985 would be 40 years and the oldest would be 64 years. That was according to a study performed in Canada. Today, we see that our average of our patients with MS are in the 60s, and we have patients who are in their 80s and 90s that still have MS and have a good quality of life.

That being said, the next progress will be to shift the idea that our patients with MS are no longer just these young, working individuals in their 20s to 40s, but that the population today is significantly more aging with their diseases and comorbidities they may have. This is in their 60s, 70s, and 80s. We have to think about cognitive impairments and any comorbidities or potentially coexisting diseases, like mild cognitive impairment or Alzheimer disease, going forward. There’s very little in the literature, and all our information is based on our younger patients and younger disability impairments, but we need to be better centered to what we see in the clinic, and that is this much older population.

Is there anything else related to your work that you’d like to share?

There’s good progress currently in terms of PCORI or NIH-funded trials looking at the aging population, and this is becoming a little bit more relevant in today’s age. Do we treat aging population? This has been a big topic in the multiple sclerosis world because we used to believe—or still believe—that the therapies that we’re using might not necessarily work on this aging population, but we see that there is a significant progression on both physical and cognitive domains in these patients with MS.

We wonder whether we should continue treating or not. This should always be a risk versus gain balanced type of game where we have to assess the risk for giving this immunosuppressive therapy to our aging patients with MS versus the benefit that they might get. The better we understand what deficits they accumulate as they age, the better we can address this risk versus gain decision that we we’re going to make on a daily basis. That’s on aspect going forward.

Secondly, there are probably only 25 case reports or case series published on multiple sclerosis concurrently having Alzheimer disease. We know that we have approximately 2.5 million patients with MS in the world and our average age for these patients is 65 years old, with some patients up to 90 years old. But we do not have this coexistence with Alzheimer disease, which is an even more common disease. Should we start screening our patients with MS for cognitive decline that are more specific for other diseases? Because we haven’t screened for this before, and maybe there’s some undiagnosed cognitive declines of different nature in our patients with MS that may or may not respond to treatment if we understand that this is coming from a different disease, not from their MS, and vice versa.

The ideal case scenario in a clinic would be if you had a 70-year-old patient with MS coming in with new onset of cognitive decline, this patient already has had MS for 40, is now off therapy, and experiences significant cognitive decline. Given that his age is 70 years old, there can be 3 major drivers of cognitive decline. It could be progression of the MS disease itself, which we should be able to address. This patient should not be excluded for new onset of mild cognitive impairment or Alzheimer disease because he fits in the age for something like that. There also could be small vascular infarct or small vascular attack that might drive that.

Ideally, we need to come up with a cognitive battery of investigating our patients at this certain age and somehow find clinical and neuropsychological differences in whether this cognitive decline is coming from progression of MS, new onset of Alzheimer disease, or a new onset of some vascular dementia. It will be important because these conditions have very different medications and a different way on how you address them going forward. We cannot have a case where we have a 70-year-old patient with MS with 40 years of MS disease and attribute the cognitive decline right away to the progression of MS, without consideration of any other aspects out there.

Transcript edited for clarity.