Objective: To explore possible correlations between levels of microglial activation (neuroinflammation) in the Substantia Innominata (SI), the major source of cholinergic input to the cortex, and cortical acethylcholinesterase activity in patients with REM sleep behavior disorder (RBD).

Background: We have previously reported the presence of reduced cortical acethylcholinesterase activity, as measured by 11C-Donepezil PET, in patients with RBD, suggesting dysfunction of the cholinergic projections from the SI to the cortex. In the same patients we have also detected increased levels of microglial activation in the substantia nigra, the occipital cortex, and, at a lesser extent, in the striatum. The cholinergic dysfunction observed in these patients could be related to an increased load of microglial activation in the SI but this has not yet been investigated.

Method: We studied 17 patients with polysomnography-confirmed RBD with 11C-PK11195 PET, a marker of microglial activation, and 11C-Donepezil PET, a marker of cholinergic function. The PNEURO module of PMOD software v 3.6 (PMOD technologies Ltd. Switzerland) was used to create a Region of interest (ROI) template encompassing the SI in Hammers atlas space, while the cortical regions were defined using the Hammers-1mm probabilistic atlas implemented in PMOD. The 11C-PK11195 binding potentials (BPND) and 11C-Donepezil distribution volume ratio (DVR) values were correlated using Pearson test.

Results: We found a significant negative correlation between 11C-PK11195 BPND values in the SI and cortical 11C-Donepezil DVR values (r = -0.4606, p = 0.03). Higher 11C-PK11195 BPND values in the SI were correlated with lower 11C-Donepezil DVR in the cortex.

Conclusion: Our results suggest that increased microglial activation in the SI of RBD patients could be associated with reduced acetylcholinesterase activity in the cortical areas receiving cholinergic projections from the SI. Longitudinal studies will help clarify if these changes could contribute to the development of cognitive impairment in these patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cortical-cholinergic-dysfunction-correlates-with-microglial-activation-in-the-substantia-innominata-in-patients-with-rem-sleep-behavior-disorder/