Perspective from Tirisham Gyang, MD
Disclosures: Huiskamp reports receiving support from the Dutch MS Research Foundation. Please see the study for all other authors’ relevant financial disclosures.
June 21, 2021
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One-fifth of patients with MS convert to a worse cognitive phenotype within 5 years

Perspective from Tirisham Gyang, MD
Disclosures: Huiskamp reports receiving support from the Dutch MS Research Foundation. Please see the study for all other authors’ relevant financial disclosures.
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Approximately one-fifth of patients with MS exhibited a deterioration in cognitive status over 5 years, according to results of a cohort study conducted in the Netherlands and published in Neurology.

“Cognitive impairment occurs in 40-70% of [patients with MS] and has severe consequences for daily life,” Marijn Huiskamp, MSc, of the department of anatomy and neurosciences at Vrije University Amsterdam in the Netherlands, and colleagues wrote. “Despite recent efforts to characterize the course of cognitive decline, it is still unknown which mechanisms constitute the conversion from preserved cognition to mild or severe [cognitive impairment], and who is at risk, hampering the provision of adequate and timely care. While longitudinal studies remain scarce, grey and white matter damage are known to relate to cognitive decline.”

Functional network dysfunction may play a significant role in these deficits, according to the researchers. Specifically, prior research implicated the default-mode network, which is regulated in part by the ventral attention network, as a significant network of interest for cognition.

In the current study, Huiskamp and colleagues sought to pinpoint functional network changes associated with conversion to cognitive impairment among 227 patients with MS (67.4% women; mean age, 47.6 years; mean disease duration, 14.8 years) and 59 healthy controls (52.5% women; mean age, 46 years) who were included in the Amsterdam MS cohort. Patients underwent neuropsychological testing and resting state functional MRI at two time points 5 years apart. At both baseline and follow-up, researchers categorized 123 patients as cognitively preserved, 32 as mildly impaired and 72 as impaired and calculated longitudinal conversion between groups. They used eigenvector centrality, which evaluates regional network importance, to quantify network function. They computed this measure for individual resting-state networks at both time points.

Results showed conversion to a worse phenotype among 18.9% of patients. Among patients initially categorized as cognitively preserved, 17.9% converted from this state to mild cognitive impairment and 8.1% to cognitive impairment. Among patients initially categorized as having mild cognitive impairment, 37.5% converted to cognitive impairment. The researchers observed higher default-mode network centrality at baseline among those with cognitive impairment compared with controls (P = .05). Among those with cognitive preservation, ventral attention network importance increased longitudinally, driven by stable cognitive preservation and cognitive preservation-to-mild cognitive impairment converters (P < .05).

The researchers wrote that the findings have “value for clinical application.” However, they also noted that the thresholds for defining cognitive conversion need to be validated in other cohorts before they are used outside of research.

“Our results could indicate that in MS, normal processes crucial for maintaining overall network stability are progressively disrupted as patients clinically progress,” Huiskamp and colleagues wrote. “This stresses the importance of future longitudinal studies in MS, in order to confirm our hypothesis on the role of the [ventral attention network] in early stages of clinical progression, as well as the [default-mode network] and other attention/executive networks in later stages.”