BACKGROUND: Impaired information processing speed (IPS) is a common and disabling cognitive deficit in multiple sclerosis (MS). OBJECTIVES: To assess whether glial activation measured using translocator protein-positron emission tomography (TSPO-PET) predicts performance and long-term change on the Symbol Digit Modalities Test (SDMT). METHODS: Forty-eight people with MS underwent ¹¹CPK11195 TSPO-PET, magnetic resonance imaging (MRI), diffusion tensor imaging and SDMT at baseline; 34 repeated SDMT a median (first to third quartile) 4.9 (3.7-5.2) years later. Glial activation was quantified using the distribution volume ratio (DVR). Multivariable regression models were used to identify predictors of baseline SDMT and subsequent change. RESULTS: Normal-appearing white matter (NAWM) radial diffusivity (estimate 95% confidence interval (CI) -129 -214, -44), thalamic DVR (-52.5 -94.8, -10.2) and age (-0.57 -1.07, -0.06) explained 41% of baseline SDMT variance. NAWM DVR was the strongest predictor of SDMT change, explaining 53% of variance when adjusted for baseline SDMT (-6.23 -8.55, -3.91). A model including lesion rim DVR (odds ratio 1.36 1.06, 1.73) and baseline SDMT (1.18 1.01, 1.37) predicted SDMT decline with 73% sensitivity and 83% specificity (area under the curve AUC = 0.85). CONCLUSION: Diffuse neuroinflammation in the NAWM is associated with future SDMT change, suggesting a potential role for chronic glial activation in IPS deterioration in MS.
Saraste et al. (2026) studied this question.