Intrathecal B cell activation and memory impairment in multiple sclerosis

Area of Science:

• Neuroimmunology
• Cognitive Neuroscience

Background:

• Cognitive impairment (CI) is a significant disability in people with multiple sclerosis (pwMS).
• The precise mechanisms driving CI in pwMS are not fully understood, with a potential role for immune cells in the central nervous system.
• This study investigated the link between intrathecal B cells and cognitive function in pwMS.

Purpose of the Study:

• To explore the hypothesis that intrathecal B cells influence cognitive performance in pwMS.
• To assess the relationship between B cell activation markers in cerebrospinal fluid (CSF) and cognitive test results.
• To determine if intrathecal B cell activity is associated with cognitive impairment independently of MRI-visible brain damage.

Main Methods:

• Retrospective analysis of 39 newly diagnosed pwMS with available CSF.
• Measurement of the kappa (κ)-index as a biomarker for intrathecal B cell activation.
• Cognitive assessment using the Brief Repeatable Battery of Neuropsychological Tests (BRBN).
• Quantification of MRI-derived metrics including T2 lesion load and brain volumes.

Main Results:

• A significantly higher κ-index was observed in pwMS with verbal memory impairment.
• The κ-index showed a negative association with BRBN tests measuring verbal memory and information processing speed.
• Multivariate analyses confirmed that a higher κ-index was independently associated with poorer verbal memory performance and increased likelihood of verbal memory impairment.

Conclusions:

• Intrathecal B cell activation may be a key driver of verbal memory impairment in pwMS.
• This association appears to be independent of the extent of MRI-detectable brain damage.
• Targeting intrathecal B cells could be a potential therapeutic strategy for cognitive dysfunction in multiple sclerosis.