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Cognitive impairment without physical disability in multiple sclerosis (MS) may grow in prevalence as newer therapies better control patients’ motor symptoms.
But the “cognitive-predominant” MS that is likely to be increasingly evident will be a greater challenge to identify and treat, and should now be a clinical and research priority, an analysis study reports.
Findings from this analysis, led by Claire Riley, MD, a professor of neurology at Columbia University, were presented by Riley at the ACTRIMS Forum 2021, in the talk “Cerebral/Cognitive-Predominant MS.”
Cognitive and physical impairment typically progress together, if to varying degrees, in MS patients. Cognitive difficulties — experienced by some 40% to 70% of patients, depending on the study referenced — often involve problems in processing speed and memory.
A small proportion of MS patients, however, appear to experience cognitive declines without motor, sensory, or other so-called cerebellar deficits. (The cerebellum is the part of the brain responsible for coordinating voluntary movements and such motor skills as balance, coordination, and posture.)
Such cognitive-dominant decline presents a diagnostic and therapeutic challenge, Riley reported, as its symptoms can be difficult to tell apart from other neurological disorder.
Early cognitive deterioration also appears to disproportionally affect children. Young people with early-onset MS tend to experience greater cognitive impairment related to information processing, broadly defined as how a person sees, understands, analyzes, and remembers things.
“As you can imagine, this is particularly problematic during educational attainment,” Riley said. “Children then, are really setting the course for their professional or vocational lives, so it is a critical time both in social and educational development.”
This, she added, makes promptly recognizing the cognitive impacts of MS all the more important.
In an effort to identify the distinguishing features of people with “cognitive-predominant” MS, Riley and her colleagues examined relapsing MS patients participating in two ongoing studies — MEM CONNECT, and Reserve Against Disability in Early Multiple Sclerosis (RADIEMS).
Despite minimal physical disability among 166 recently diagnosed MS patients in the RADIEMS study — defined by an Expanded Disability Status Scale (EDSS) scores of no more than 2.5, and a timed 25-foot walk (T25FW) of under five seconds — these patients were more than twice as likely to score poorly (16.9% ) on the Symbol Digit Modality Test (SDMT) than were their healthy, matched peers (6.0%). (SDMT is a validated test of cognitive impairment in MS, with poorer scores indicative of greater impairment.)
Patients with poorer SDMT scores also had greater T2 lesion volumes — a measure of active inflammation in the brain — and greater loss of gray and thalamic brain matter volumes.
Interestingly, these findings of physical changes to the brain appeared to relate more to its left hemisphere. This left-vs-right hemisphere pattern also appeared to correlate specifically with SDMT scores, showing no strong association with EDSS or the T25FW.
SDMT scores among MEM CONNECT patients — who were generally older and had longer MS durations — did not differ significantly between those with low and high physical disability, although for reasons that remain unclear. Further study here is needed in a larger group of these patients, Riley said.
“In sum,” she continued, “I think cognitive-predominant MS may become more prevalent … based on [our] improved control of major motor relapses,” through, for instance, the use of high-efficacy therapies.
“The cognitive features of MS do impact many [people] and often begin in the earliest phases of the disease,” as was seen in children and pre-symptomatic patients, Riley added. “Attending to these cognitive outcomes both in our clinical trials and clinical practice now may pay dividends in the future.”
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