Multiple sclerosis (MS) is associated with cognitive and social cognitive deficits. Social cognition impairments may include difficulty with facial expression and emotion recognition. People with MS (PwMS) may also not be aware of their cognitive challenges as demonstrated through discrepant objective and subjective assessments. Research recently conducted in demyelinated mouse models demonstrated that metformin, a drug typically used to treat type II diabetes mellitus (DMII), promotes remyelination and reverses existent social cognition impairment by repressing the monoacylglycerol lipase (MgII) enzyme in the brain. We aim to translate this basic science research and are conducting a pilot study to determine if metformin improves social cognition in PwMS. This project will compare social cognition in those with MS and comorbid DMII who are treated with metformin and those who are not. For the purposes of this interim data analysis, we collapse across both MS groups who are, and who are not, treated with metformin. The current objective is to evaluate the relationship between subjective (i.e., perceived empathy), objective social cognition and information processing speed (IPS) in PwMS and co-morbid diabetes.

Preliminary data on 15 PwMS are included. Participants completed a demographic questionnaire, a cognitive assessment battery, an objective social cognition assessment and self-report questionnaires. These questionnaires assessed subjective social cognition, fatigue, mood, and disability level.

Preliminary results showed that IPS was positively correlated with the affective empathy domain of social cognition, r = .53, p = .04. Additionally, IPS was positively correlated with objective social cognition, r = .71, p = 003. Follow-up regression analyses demonstrated that IPS predicted objective social cognition, R2 = .71, SE = 3.04, F(1,13) = 13.36, p = .003 and subjective social cognition, R2 = .53, SE = 5.39, F(1,13) = 4.97, p = .04. However, subjective and objective measures of social cognition were not correlated, p > .05 and remained uncorrelated when IPS was controlled for, p > .05.

A majority of the variance in social perception is explained by IPS, suggesting that how quickly one can think may be a fundamental cognitive process to allow optimal functioning in social situations. While the reason for the relationship between IPS and subjective social cognition is perhaps less apparent, it may reflect a more global cognitive compromise that impacts both cognitive and social processes. This lends support to the Relative Consequence Model that suggests IPS deficits are a fundamental cognitive deficit underlying other more complex cognitive processes. The lack of correlation between subjective perception of empathy and objective social cognition requires further exploration and could potentially be related to some individuals with MS having a diminished ability to judge their own social proficiency. Further analyses with a larger sample will be conducted to assess group differences in social cognitive outcomes and MgII levels between metformin and non-metformin groups. If PwMS who take metformin have better social cognition compared to PwMS who do not take metformin, Mgll levels can be used as a biomarker to guide metformin treatment with the goal of improving social cognition.