Study Identifies Potential Biomarkers for MS-Related Cognitive Decline

Results of an observational study suggest retinal nerve fiber layer atrophy and the presence of oligoclonal bands may serve as biomarkers for cognitive decline in patients with multiple sclerosis (MS).

Retinal nerve fiber layer (RNFL) atrophy and the presence of oligoclonal bands (OCBs) were related to cognitive decline in patients with multiple sclerosis (MS) over a 5-year follow-up period, according to results of an observational cohort study. The findings, published in Frontiers in Neurology, suggest these 2 factors may serve as potential biomarkers for cognitive decline in MS.

Although it remains unknown whether early degeneration is an independent process in MS or is secondary to inflammation, “understanding the mechanism and causes of neurodegeneration in MS may be fundamental to developing therapies that can help halt this process and presumably prevent the progression of disability,” authors explained.

To assess the impact of both neurodegenerative and inflammatory markers on cognitive decline among patients with MS, investigators conducted a prospective, single-center, observational cohort study at a university in Lithuania.

Between 2012 and 2019, patients between the ages of 18 and 60 years with relapsing-remitting MS underwent physical and neurological examinations including the Brief International Cognitive Assessment for MS (BICAMS), ophthalmological examinations using optical coherence tomography (OCT), and brain magnetic resonance imaging (MRI). After 5 years, the same tests were performed again.

Of the 63 patients originally enrolled, 5-year follow-up data were available for 49 individuals.

Analyses revealed:

  • A significant reduction in information processing speed, visual learning, temporal RNFL thickness, the Huckman index, and third ventricle mean diameter was found in all 49 patients with relapsing MS over the observation period (P < .05)
  • Of the patients, 63.3% had positive OCBs and 59.2% had elevated immunoglobin G (IgG) indices
  • The atrophy of the temporal segment and papillomacular bundle (PMB) and the presence of OCBs were significantly related to a decline in information processing speed in these patients (P < .05)
  • Brain atrophy markers were not found to be significant on the general linear models

Despite finding that OCBs and elevated IgG indices were not correlated with each other, researchers noted both are biomarkers of inflammation and are supportive of an MS diagnosis.

“The absence of such a correlation is possible because OCBs reflect the production of several monoclones, while the IgG index is a general indicator of enhanced autoimmune response,” they wrote.

Authors also found the average thickness in the temporal segment and PMB in both eyes constituted the most important OCT measure related to cognitive decline in study participants.

The study’s relatively small sample size and lack of control group mark limitations to the current analysis.

“Our results confirm that the BICAMS and OCT measure different aspects of neurodegeneration and that the thinning of the RNFL is a potential biomarker for cognitive disability in MS, because we found that cognitive decline may be predicted not only by markers of degeneration but also by markers of intrathecal inflammation,” researchers said.

“These results imply that both the thinning of the RNFL and the presence of CSF-OCBs are feasible biomarkers for cognitive decline in MS,” they concluded.


Giedraitiene N, Drukteiniene E, Kizlaitiene R, Cimbalas A, Asoklis R, and Kaubrys G. Cognitive decline in multiple sclerosis is related to the progression of retinal atrophy and presence of oligoclonal bands: a 5-year follow-up study. Front Neurol. Published online July 13, 2021. doi:10.3389/fneur.2021.678735

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