Worsened Cognition in Multiple Sclerosis Related to Ventral Attention Network

Disease Spotlight | <b>Disease Spotlight: Multiple Sclerosis</b>

At baseline, a negative correlation was noted between average cognition and VAN importance in both groups, indicating that lower VAN importance is related to a higher average cognition.

Investigators evaluating cognitive status change in patients with multiple sclerosis (MS) found that conversion from intact cognition to impairment over a 5-year stretch was related to an initial disturbed function of the ventral attention network (VAN), then shifting towards default-mode network (DMN) dysfunction in patients with cognitive impairment (CI).

Senior author Menno M. Schoonheim, PhD, assistant professor, Amsterdam University Medical Center, and colleagues concluded that, “as the VAN normally relays information to the DMN, these results could indicate that in MS, normal processes crucial for maintaining overall network stability are progressively disrupted as patients clinically progress.”

To characterize functional network changes related to conversion to CI, investigators collected data from 227 patients with MS and 59 healthy controls (HCs) of the Amsterdam MS cohort. At both baseline and follow-up, patients were categorized as cognitively preserved (CP; n = 123), mildly impaired (MCI; n = 32), or CI (n = 72). Longitudinal conversion between the groups was determined and network function was quantified using eigenvector centrality.

Of all patients, 19% worsened in their cognitive status over 5 years. At follow-up, the distribution over the cognitive groups changed, resulting in a total of 104 CP (45.8%), 51 MCI (22.5%), and 72 CI (31.7%) patients. In total, 32 CP patients (26%) deteriorated and converted to MCI (n = 22) or to CI (n = 10).

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In patients that remained cognitively preserved (CP–CP) and in those converting to MCI (CP–MCI), VAN centrality increased over time (P = .017 and P = .008, respectively), whereas no change was observed in the CP®CI group. No significant effects were observed in the connectivity between the VAN and other cognitive networks.

A negative correlation between average cognition and VAN importance was observed at baseline in both the HC and MS groups (r = –0.33, P = .014; r = –0.14, P = .045, respectively), indicating that a lower VAN importance is related to a higher average cognition. Investigators also noticed a positive relationship between delta VAN importance and average cognition at baseline in those with MS (r = 0.18; P = .006), indicating that higher average cognition at baseline correlated to a stronger increase in VAN importance over time.

Significant differences were noticed in post-hoc testing between CI and CP patients in the visual network (i.e., lower in the CI than in the CP; P = .013) and in the DMN (i.e., higher in the CI than in CP; P = .05). A group time interaction effect was noted in the VAN (F[3277] = 3.60; P = .014) and in the cerebellum (F[3277] = 2.81; P = .040); however, post-hoc tests showed an opposite effect over time only in the CP patients, with an increasing VAN centrality (P = .001), but decreasing cerebellum centrality (P <.001). Notably, none of the other groups defined at baseline showed significant changes in the VAN or cerebellum.

At baseline, VAN-DMN and VAN-FPN (frontoparietal network) connectivity was only increase in the CI group as compared to the CP and HC groups (VAN-DMN: P = .032 and P = .018; VAN-FPN: P = .010 and P = .034, respectively), while VAN-DAN (dorsal attention network) connectivity was only higher in CI compared to the HC group (P = .026).

Huiskamp M, Eijelers AJC, Broeders TA, et al. Longitudinal network changes and conversion to cognitive impairment in multiple sclerosis. Neurology. Published online June 7, 2021. Doi: 10.1212/WNL.0000000000012341