TSPO-PET-measurable neuroinflammation associates with information processing speed decline in multiple sclerosis

Area of Science:

• Neuroimaging
• Neuroinflammation
• Cognitive Neuroscience

Background:

• Impaired information processing speed (IPS) is a common and disabling cognitive deficit in multiple sclerosis (MS).
• Identifying biomarkers for IPS decline is crucial for managing MS.
• Glial activation is implicated in MS pathogenesis.

Purpose of the Study:

• To assess if glial activation, measured using translocator protein-positron emission tomography (TSPO-PET), predicts current performance and long-term changes in the Symbol Digit Modalities Test (SDMT).
• To investigate the relationship between neuroinflammation and cognitive function in MS patients.

Main Methods:

• Forty-eight people with MS underwent TSPO-PET, MRI, diffusion tensor imaging, and SDMT at baseline.
• Thirty-four participants repeated the SDMT after a median of 4.9 years.
• Glial activation was quantified using distribution volume ratio (DVR); multivariable regression models identified predictors of SDMT performance and change.

Main Results:

• Normal-appearing white matter (NAWM) radial diffusivity, thalamic TSPO-PET DVR, and age explained 41% of baseline SDMT variance.
• NAWM DVR was the strongest predictor of SDMT change, explaining 53% of variance.
• A model including lesion rim DVR and baseline SDMT predicted SDMT decline with 73% sensitivity and 83% specificity (AUC=0.85).

Conclusions:

• Diffuse neuroinflammation in NAWM is associated with future SDMT decline in MS.
• Chronic glial activation in the brain may contribute to the deterioration of information processing speed in MS.
• TSPO-PET imaging shows potential as a biomarker for predicting cognitive decline in MS.