With increasing numbers of people with multiple sclerosis (MS) reaching advanced age, and therefore, more of them experiencing cognitive decline, it is now more important than ever to understand whether a person’s decline is related to their MS or, instead, to something else, like Alzheimer’s Disease (AD).

BNAC researchers led by Dejan Jakimovski, M.D. Ph.D., seek to open the door for researchers to monitor the most clinically relevant brain regions for such a diagnosis and potentially predict an individual patient’s risk for cognitive decline as well as its most appropriate treatment.

Jakimovski has been awarded a pilot research grant by the Consortium of Multiple Sclerosis Centers (CMSC) to determine which brain structures are responsible for specific types of cognitive decline in 100 aging MS patients.

MS Now Most Prevalent in Older People

Traditionally, multiple sclerosis was regarded as a disease that typically presents in the young and working population. Yet over the past three decades, potent anti-inflammatory disease modifying therapies (DMTs) have significantly improved the life expectancy of people with MS and changed the overall epidemiological profile of this population.

Based on the most recent U.S.-based administrative claims data, the highest prevalence of MS patients is found in women and men aged 55-64 years (24 percent of all patients), followed by 65-74 years (13 percent).

While neurodegenerative MS brain changes and their relationship with cognitive performance has been investigated in younger and mid-life people with MS (e.g., thalamus and cognitive processing speed), no such data are available for the growing elderly MS population.

Up to 60 Percent of Older MS Patients Experience Cognitive Impairment; But What Kind?

With the rising median age of people with MS, increasing numbers (up to 60 percent within older and secondary progressive MS patients) present with cognitive impairment. They exhibit particular deficits within the domains of processing speed, visuospatial memory, and/or executive function.  

Research is only beginning to determine if the cognitive decline in an aging person with MS is attributable simply to MS worsening, or instead, to onset of mild cognitive impairment (MCI), Alzheimer’s Disease, or vascular dementia.

As more people with MS reach old age, it is likely that some may experience the types of cognitive impairment experienced by those with Alzheimer Disease.

In two separate preliminary cognitive investigations of elderly people with MS, BNAC researchers observed impairment in the cognitive domain of “categorical verbal fluency,” as evidenced by the ability to produce as many words as they can in a specific category (e.g., supermarket items or animals) over a period of one minute. This particular impairment is not commonly seen in the young MS population.

Impairments in the language domain are commonly considered part of an AD-based cognitive phenotype. The cognitively impaired MS group showed evidence of a deficit in this domain that was comparable to patients with amnestic mild cognitive impairment (MCI) due to AD, when there are obvious symptoms of brain dysfunction. Moreover, the verbal fluency impairment was also seen in a recent and rare case report of concurrent Alzheimer’s and MS disease.

So, is the cognitive decline due to MS or AD? Determining the nature of the language impairment and its association with specific structural MS changes will allow better understanding of this particular dysfunction in aging MS patients.

The Research

Jakimovski and his colleagues will analyze the anatomical features of decline—certain gray matter structures, such as the thickness of cortical areas and the volume of deep gray matter nuclei and their relationship with different cognitive domains (learning and memory, visuospatial function, executive function, attention/concentration/ processing speed, and language) for the first time among elderly people with MS.

If aging and neurodegenerative mechanisms drive the cognitive decline in older MS patients, the test performance of the patients will be correlated with thinning of already known cognition-specific cortical areas (tempoparietal lobe, and in particular, cingulate and entorhinal cortex). On the other hand, if MS pathology drives the cognitive decline in aging MS patients, the performance will remain dependent on deep gray structures with large number of intersecting axons such as the thalamus.

Jakimovski hypothesizes that the previously established relationship between deep gray matter structures (i.e. thalamus) may not be associated with the performance within the verbal fluency domain of aging MS patients. Rather, that the new deficits seen in this population will correlate with the thickness and surface of their cortex.

The research aims:

• To determine/quantify the patterns and extent of neurodegenerative changes (global brain volume changes and cortical thinning) in elderly MS patients with long-standing disease;
• To determine specific spatial relationships between the global brain volumes and the cortical thickness of 86 brain regions and cognitive domain-specific performance in the elderly MS population; and
• Based on these findings, to compare the structure-cognition relationships within elderly MS patients (>50 years old) with previously published data regarding younger MS patients (20-50 years old).    

MRI images from 100 elderly MS patients (age ≥50 years old) with previously available neuropsychological assessment will be analyzed. All patients were previously examined by experienced neurologist and their disability scored based on the Expanded Disability Status Scale (EDSS). Moreover, the patients also will be scored by the Multiple Sclerosis Severity Score (MSSS).

The neuropsychological profiling includes an MS-specific battery named Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS), which evaluates cognitive processing speed, learning and memory, language, and executive function. AD-specific cognitive tests will include Logical Memory from Wechsler Memory Scale-Revised (WMS-R), two categories of semantic fluency (total number of categorical items generated in one minute; animals and supermarket items), Boston Naming Test (BNT), Beery Visual-Motor Integration (VMI), and clock drawing test.

In addition to the raw scores, the neuropsychological performance on each test of the patients will be calculated based on performance of age and sex-matched healthy controls.

Building on BNAC Research

The CMSC-funded research builds on other studies performed by Jakimovski and his colleagues at the University of Buffalo’s 21-year-old Buffalo Neuroimaging Analysis Center, led by Center Director Robert Zivadinov, M.D., Ph.D.

 

A list of published papers along with contact information can be found elsewhere on BNAC.net.

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