Cognitive Dysfunction Found to Increase Risk of Death in MS

Yedida Y Bogachkov PhD avatar

by Yedida Y Bogachkov PhD |

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Cognitive dysfunction in patients with multiple sclerosis (MS) is predictive of worse outcomes, including clinical progression of the disease and a higher risk of mortality, according to a new study.

“This review revealed that cognitive dysfunction … was associated with higher odds of transitioning from [a] relapsing–remitting course to a progressive disease course … and [a] higher hazard of death,” the researchers wrote.

The study, “Cognitive dysfunction and mortality in multiple sclerosis: Long-term retrospective review,” was published in the Multiple Sclerosis Journal.

MS is a disease of the central nervous system characterized by inflammation and neurodegeneration. Cognitive impairment, or dysfunction, is recognized as a core feature of the disease. It can occur early in the disease process, and is more severe and frequent among patients with progressive forms of MS.

Such cognitive impairment can lead to lower employment rates, social limitations, and poorer quality of life. Additionally, some long-term studies have shown that cognitive impairment may be a predictor of disease progression, although its potential use as a predictor of mortality in MS patients has been inconclusive.

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Now, researchers in Portugal explored the prognostic value of cognitive dysfunction for disease progression and survival rates by reviewing data from a group of 408 MS patients over the course of up to 15 years. Patient records were retrospectively analyzed in December 2020, and data was available as far back as May 2005; the patients also had been assessed in August 2012.

“We hypothesized that cognitive dysfunction is predictive of greater clinical progression and lower survival,” the researchers wrote.

In the group analyzed, 77 patients (19%) had cognitive dysfunction at the start of the study. Furthermore, 10% of them were at increased risk for dementia, 26% had anxiety, and 12% had depression. The group with impairments had fewer years of education than those without.

Those with cognitive dysfunction also had longer disease duration, greater disability, greater disease severity, and greater age-related disease severity at the study’s start relative to patients without such impairment.

At the start of the study, cognitive dysfunction was more frequent in patients with progressive disease and depression.

Regarding disease types, cognition concerns were seen at the study’s start in 48% of those with secondary progressive MS (SPMS), 21% of those with primary progressive MS (PPMS), and 15% of those with relapsing-remitting MS (RRMS). Those findings indicated that patients with progressive disease were more likely to experience cognitive dysfunction.

Over the course of follow-up, 40 patients with RRMS converted to SPMS, with a median of 50 months (over four years) between the start of the study and conversion to a progressive disease course. The range, in months, was between 6 and 180 months, or 15 years.

In total, among RRMS patients, 21% of those with cognitive dysfunction at the start of the study converted to SPMS versus 11% of those without impairment at the study’s launch.

“The odds of converting to SPMS, while taking into account the follow-up interval, were higher for patients with cognitive dysfunction,” the researchers wrote.

The team also found that cognitive impairment at the start of the study was related to greater disability and disease severity at follow-up.

“The study results revealed that cognitive dysfunction was related to greater physical disability both at the time of the assessment and at follow-up,” the investigators wrote.

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Patients with progressive disease and cognitive dysfunction at the study start had a larger change per month in their disease severity than those without such impairment, based on the MS severity scale (MSSS) — a scale for assessing disease severity in patients with MS. Meanwhile, no clinical change was seen in the per month measurements in those with RRMS, whether they had cognitive dysfunction or not at the study start.

Concerning survival rates, at the time of the last clinical contact, 29 deaths (7% of the group) had been recorded. Of those, 14 patients had severe infections requiring hospitalization, six had sudden death, and four had a co-existing cancer. One patient had a stroke, one had kidney failure, one had liver failure due to autoimmune hepatitis, and the causes for two other patients’ deaths were unknown.

A breakdown by disease subtype revealed that, over the course of follow-up, 3% of those with RRMS died, as did 24% of those with SPMS, and 18% of those with PPMS. At the time of death, the patients’ ages ranged from 30 to 76, with a median age of 59.

A total of 17% (13 of 77) of patients with dysfunction at the study’s start died, compared with 5% of those without such symptoms, suggesting that mortality rates were higher for those with cognitive issues.

“The association between cognitive dysfunction and survival remained statistically significant … when demographic and clinical covariates (i.e. sex, age, education, autoimmune comorbidities …) were taken into consideration,” the researchers wrote.

Overall, the team found a host of predictive factors for a shorter survival across the analyzed group. Specifically, older age, lower education, older age at disease onset, longer disease duration, greater disability, greater disease severity, and progressive disease course all were associated with a greater risk of mortality for these patients.

Notably, when divided by subgroup, the increased mortality risk for those with cognitive dysfunction was not significant for those with RRMS when demographic and clinical covariates — sex, age, education, disease duration, disability, and anxiety and depression scores, among others — were taken into account, although it was still significant for those with progressive MS.

Based on the results, the team concluded that “cognitive dysfunction was predictive of conversion to secondary progressive course, greater clinical decline in patients with progressive course, and higher hazard of death.”

“These data provide compelling evidence for the use of cognition in MS as a marker of long-term disease evolution and prognosis and a predictor of survival,” the researchers wrote.

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