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

Mov Disord. 2024 Mar 13. doi: 10.1002/mds.29767. Online ahead of print.

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 Ki changes from baseline were evaluated with volumes-of-interest and voxel-based analyses.

Results: Significant 18 F-DOPA Ki 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 Ki 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.

Keywords: Parkinson's disease; REM sleep behavior disorder; neuroimaging; neuroinflammation.