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

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 [¹¹C]PK11195 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.