Cognitive impairment in relapsing remitting multiple sclerosis patients: the role of white matter.
Mahmoud Elkhooly1, Fen Bao1, Adam Lazar1, Zena Azo1, Amanda Reyes1, Samiksha Srivastava1, Emily Pelc1, Chiara Casiglia1, Jacob Rube1, Muhammed Raghib1, Carla Santiago-Martinez1, Shireen Khan1, Evanthia Bernitsas1
1Neurology, Wayne State University
Objective:
To investigate the relationship between cognition and white matter (WM) in relapsing remitting (RRMS) patients.
Background:
Cognition is thought to be mainly associated with gray matter injury in MS. The role of WM tracts in MS-cognitive impairment is still uncertain.
Design/Methods:

Thirty RRMS patients were recruited and underwent the 3-seconds-interstimulus interval paced auditory serial addition test (PASAT-3), symbol digit modalities test (SDMT), and whole brain MRI scan on a SIEMENS 3 Tesla Verio scanner. Diffusion tensor imaging (DTI) metrics including fractional anisotropy (FA) and mean diffusivity (MD) were measured in 37 WM regions selected from association, projection, and commissural pathways, by applying Human Connectome Project (HCP)842 tractography atlas after DTI data reconstruction and registration to HCP1065 diffusion template were performed in DSI Studio (version March 2021). Spearman’s rank correlation analysis was performed to investigate the relationship between DTI WM tracts and cognitive scores in SPSS v26. False discovery rate (FDR) calculation was done to decrease the false positives and increase the power of the study.

Results:

Mean PASAT-3 and SDMT scores were 31.5 ±12.8 and 46.9 ±16.7 respectively. Higher FA values were associated with better cognitive function, while higher MD values were associated with worse cognitive function. FA values in right medial lemniscus and superior cerebellar peduncle were positively correlated with SDMT scores (p<0.05), while a strong trend for significance was found for the left corticothalamic tract (p=0.05). MD values of the superior cerebellar peduncle, left arcuate fasciculus and left extreme capsule were negatively correlated with SDMT scores (p<0.05), while MD value of the right cerebellum was negatively correlated with PASAT-3 score.  No significant correlation was found between FA values and PASAT-3 scores.

Conclusions:
Our data support the contribution of certain WM tracts to the cognitive impairment in RRMS. Longitudinal studies with larger samples are warranted.
10.1212/WNL.0000000000202781