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

Abstract Background Using 11 C‐(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 11 C‐(R)‐PK11195 and 18 F‐DOPA‐PET underwent repeat 18 F‐DOPA‐PET after 3 years. 18 F‐DOPA K i changes from baseline were evaluated with volumes‐of‐interest and voxel‐based analyses. Results Significant 18 F‐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 11 C‐(R)‐PK11195 binding at baseline was a predictor of 18 F‐DOPA K i reduction in left caudate (coef = −0.0426, P = 0.016). Conclusions Subjects with increased baseline 11 C‐(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. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.