Objective: To assess the role of early microglial activation on the progression of nigrostriatal dysfunction, measured with ¹⁸F-DOPA PET, in isolated REM sleep behavior disorder (iRBD) patients.

Background: IRBD is widely considered a synucleinopathy and a prodromal phenotype of parkinsonism. Using ¹¹C-PK11195 PET, a marker of brain microglial activation, we have previously reported the presence of neuroinflammation in the substantia nigra (SN) of iRBD patients with no clinical evidence of parkinsonism. Some of these patients also had increased ¹¹C-PK11195 binding in their striatal regions.  While the occurrence of activated microglia in these areas is indicative of ongoing pathology, it remains to be established whether it has a protective effect or contributes to the neurodegenerative process.

Method: Fifteen polysomnography-confirmed iRBD patients with no clinical evidence of parkinsonism, who received a ¹¹C-PK11195 and a ¹⁸F-DOPA PET as part of our baseline study, underwent follow-up ¹⁸F-DOPA PET after a 3-year period. Six of these patients had abnormal ¹¹C-PK11195 binding (2 SD above the control group mean) in the SN and striatum.
Parametric images of ¹⁸F-DOPA influx constants (Ki) were generated with the Patlak graphical approach using occipital lobe grey matter as nonspecific reference tissue. The follow-up and baseline images were compared at a voxel level using Statistical Parametric Mapping (SPM12) (FIL Methods Group).

Results: SPM localized significant reduction (p < 0.01, FWE corrected) in ¹⁸F-DOPA uptake from baseline to follow-up across the iRBD patients in the caudate nuclei and in the anterior portion of the putamen bilaterally. When the groups with and without abnormal ¹¹C-PK11195 binding were assessed separately, SPM (p < 0.01, FWE corrected) showed more widespread and severe changes across the striatal areas in the former group, whereas the latter only showed minimal changes in the left caudate.

Conclusion: Our results indicate that the severity and the extent of nigrostriatal dysfunction, as measured by decline in striatal ¹⁸F-DOPA uptake, increased significantly in our iRBD patients over a 3-year period.  It was more severe in the subjects who showed increased baseline microglial activation in the nigrostriatal pathway. This would suggest a detrimental rather than a neuroprotective effect of neuroinflammation even in the early stages of parkinsonism.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/microglial-activation-associated-with-a-faster-progression-of-nigrostriatal-dysfunction-in-patients-with-isolated-rem-sleep-behavior-disorder/