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.