Microglial Activation and Progression of Nigrostriatal Dysfunction in Isolated REM Sleep Behavior Disorder

Background: Using C-11-(R)-PK11195-PET, we found increased microglia activation in isolated REM sleep behavior disorder (iRBD) patients. Their role remains to be clarified. Objectives The objective is to assess relationships between activated microglia and progression of nigrostriatal dysfunction in iRBD. Methods: Fifteen iRBD patients previously scanned with C-11-(R)-PK11195 and F-18-DOPA-PET underwent repeat F-18-DOPA-PET after 3 years. F-18-DOPA K-i changes from baseline were evaluated with volumes-of-interest and voxel-based analyses. Results: Significant F-18-DOPA K-i reductions were found in putamen and caudate. Reductions were larger and more widespread in patients with increased nigral microglia activation at baseline. Left nigral C-11-(R)-PK11195 binding at baseline was a predictor of F-18-DOPA K-i reduction in left caudate (coef = -0.0426, P = 0.016). Conclusions: Subjects with increased baseline C-11-(R)-PK11195 binding have greater changes in nigrostriatal function, suggesting a detrimental rather than protective effect of microglial activation. Alternatively, both phenomena occur in patients with prominent nigrostriatal dysfunction without a causative link. The clinical and therapeutic implications of these findings need further elucidation. (c) 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.