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Study Finds Potential Biomarkers for Cognitive Decline in MS Over 5-Year Period


Investigators found that biomarkers for neurodegeneration and inflammation could also aid providers in detecting declines in cognition and information processing speed in patients with multiple sclerosis (MS) over a 5-year period.

Retinal nerve fiber layer (RNFL) atrophy and the presence of oligoclonal bands (OCBs) in cerebrospinal fluid may be helpful biomarkers for detecting cognitive decline in patients with multiple sclerosis (MS) when assessed over a 5-year period, according to a recent study.

The results of the prospective, single-center, observational cohort study, published in Frontiers in Neurology, provided evidence for potential sensitive and accessible biomarkers for cognitive decline and established a relationship between neurodegenerative and inflammatory markers and speed of information processing.

“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,” wrote the investigators.

Cognitive impairment is present in 50% to 70% of patients with MS and can significantly lower patient quality of life. The most frequent cognitive problems observed in this population are impaired information processing speed, episodic memory, complex attention, and executive function.

It is unknown whether early degeneration is an independent process or related to inflammation in MS. Inflammation is easier to observe, assess, document, and monitor in patients, whereas neurodegeneration is more difficult, especially in patients with early-stage MS. Additionally, brain atrophy may be a useable biomarker for early neurodegeneration, but use of MRI for detecting atrophy in a routine clinical setting is challenging.

The investigators conducted their study at Vilnius University Hospital Santaros Klinikos in Lithuania and enrolled patients between 2012 and 2019 to assess the impact of different neurodegenerative markers, such as RNFL thickness and brain atrophy, and inflammatory markers, including intrathecal OCBs and the immunoglobulin G (IgG) index.

For study inclusion, the patients had to be between the ages of 18 and 60 years, have relapsing or remitting MS, be without relapse and/or steroid treatment for at least 30 days prior to assessment and during the follow-up period, be on a stable disease-modifying therapy, and have no history of MS-associated optic neuritis. All patients underwent physical and neurological examinations at baseline and again 5 years later.

In total, 63 patients were enrolled, and follow-up data were available for 49 (77.8%) patients. The mean (SD) age of the cohort was 47.3 (11.1) years, and 37 (75.5%) patients were women. Among the 49 patients with available follow-up data, 63.3% had positive OCBs and elevated IgG indices in their cerebrospinal fluid, which did not differ between sexes, by age, or by disease duration (P > .05 for all). Additionally, no relationship was detected between positive OCBs and elevated IgG indices (P > .05).

The mean RNFL thickness, observed using optical coherence tomography, in the temporal, nasal, inferotemporal, and inferonasal segments and the overall global average thickness were significantly lower in both eyes at the end of the follow-up period (P < .05). The average thickness of papillomacular bundle and superotemporal segment was smaller in the right eye and left eye, respectively, after the follow-up assessment.

The investigators used a general linear model to assess the relationship between the changes in RNFL thickness, brain atrophy markers, disability scored, OCBs, IgG index, and disease characteristics and the changes in cognitive impairments over 5 years, finding that declines in information processing speed could be explained by RNFL thickness in the temporal segment or PMB in both eyes and OCBs in cerebrospinal fluid.

The 2 limitations associated with the study included the relatively small sample size and lack of a control group.


Giedraitiene N, Drukteiniene E, Kizlaitiene R, Cimbalas A, Asoklis R, 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. 2021;12:678735. doi:10.3389/fneur.2021.678735

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