NeuroVoices: Joe Verghese, MBBS, MS, on Motor Presentations in Early Dementia

Joe Verghese, MBBS, MS

The National Institutes of Health (NIH) recently awarded 2 grants totaling $13.8 million to Joe Verghese, MBBS, MS, director of the Montefiore Einstein Center for the Aging Brain, to conduct studies on pre-dementia and Alzheimer disease (AD). The first grant totals $7.6 million over 5 years and will fund a study of motoric cognitive risk (MCR) syndrome, a pre-dementia condition in which older adults present with abnormally slow gait and cognitive complaints.

As part of NeurologyLive’s NeuroVoices series, Verghese offered insight into the unique characteristics of MCR syndrome and why its identification in the patient population could help bring the AD community 1 step closer to effective treatment and prevention.

NeurologyLive: How is motoric cognitive risk syndrome characterized? What unique symptoms does this syndrome present in comparison to other typical mild cognitive impairments?

Joe Verghese, MBBS, MS: We have increasingly recognized that there are a lot of non-cognitive features that you get early in the course of dementia. Patients have described behavioral disturbances or disturbances in smell in particular types of dementia. We have been doing research on motoric manifestations in early stage dementia. Over the last 2 decades, there has shown a lot of changes in gait in people that go on to develop dementia. They slow down, their gait becomes a small variable, and they develop clinical gait abnormalities earlier on. In our research and in clinical practice, we use this as a marker of early stages of dementia.

I do a lot of research in places of poorer setting. That includes the Bronx, where most of our research is from, but also overseas in places like India, where there is a limitation to resources. One of the biggest challenges in identifying people with cognitive impairment early is that it’s difficult to do detailed cognitive testing, or expensive assays like magnetic resonance imaging (MRI) or blood tests. Based on the knowledge we’ve gained about the connection between gait and cognition, we decided to propose a new syndrome called motoric cognitive risk syndrome. Individuals that meet the criteria for this syndrome experience cognitive complaints, including worsened memory, not thinking as clearly, and having slowed gait. This is all based on the criteria for mild cognitive impairment syndrome, which is more widely known and recognized.

The only difference is that we’ve substituted slow gait for objective cognitive testing, thus making it more accessible in many settings. Over time, we’ve learned that this syndrome is quite common in older people. We’ve collaborated with 21 different styles of studies and seen that MCR is associated with increased risk of developing dementia, Alzheimer disease, and vascular dementia. Using this simple clinical assay, we are able to screen people in poor resource settings and identify those at the highest risk of converting to dementia.

What do you hope to accomplish in your investigation of MCR? What key elements do we need to understand about this syndrome in order to better diagnose it early?

We’ve done a lot establishing the epidemiology of MCR, its prevalence, its incidence, and some of the clinical risk factors. In this new study, we’re going to probe a bit more into the pathogenesis, or the biology of MCR syndrome. We’ve targeted a few pathways. We’re looking at inflammation, oxidative stress, and vascular pathways. We're trying to see if these impairments in these pathways would lead to developing MCR which in turn would increase the risk for dementia. It has diagnostic implications in terms of identifying biomarkers that would identify people at risk for future MCR, but also might open up some therapeutic potential. Maybe if we treat some of these pathways, we can prevent MCR. Then, the hope is that by preventing MCR, we can prevent dementia as well.

The other aspect that we are looking at is the brain substrates of MCR. In order to do this study, we've brought together 6 different studies. We are pulling the data across these studies so that we have a lot sample in order to test some of these hypotheses. On the other hand, we want to look at MCR in different populations and examine its effect in that way. The risk factor in an Asian population might not be the same risk factor in a Caucasian population. I think we have greater strength in addressing some of these population heterogeneity effects.

What is the advantage of further characterizing this very specific presentation of cognitive decline?

In terms of the majority of MCR, I want to stress the clinical utility of the syndrome, and that it can be easily applied to patient populations. Even though it is derived from the current MCI and mild cognitive impairment syndrome criteria, the overlap between MCR and MCI is actually modest. There’s only about 40% of people in multi-country studies who meet criteria for both syndromes, which suggest that either syndrome alone is not capturing the huge pool of people at risk for dementia. These approaches are meant to be complimentary. We need both MCI as well as MCR approaches to identify as many people as possible.

Transcript edited for clarity.