Cortical cholinergic dysfunction correlates with microglial activation in the substantia innominata in REM sleep behavior disorder

Abstract

Introduction: In vivo PET studies in patients with isolated REM sleep behavior disorder (iRBD) have shown presence of neuroinflammation (microglial activation) in the substantia nigra, and reduced cortical acetylcholinesterase activity, suggestive of cholinergic dysfunction, that was more widespread in patients with poorer cognitive performances. This study aimed to explore whether reduced cortical acetylcholinesterase activity in iRBD is linked to microglial activation in the substantia innominata (SI), the major source of cholinergic input to the cortex.

Methods: We used ¹¹C(R)-PK11195 and ¹¹C-Donepezil PET to assess levels of activated microglia and cholinergic function, respectively, in 19 iRBD patients. ¹¹C(R)-PK11195 binding potential (BP_ND) and ¹¹C-Donepezil distribution volume ratio (DVR) values were correlated using the Pearson statistic.

Results: We found that a lower cortical ¹¹C-Donepezil DVR correlated with a higher ¹¹C(R)-PK11195 BP_ND in the SI (r = -0.48, p = 0.04). At a voxel level, the strongest negative correlations were found in the frontal and temporal lobes.

Conclusion: Our results suggest that reduced cortical acetylcholinesterase activity observed in our iRBD patients could be linked to the occurrence of neuroinflammation in the SI. Early modulation of microglial activation might therefore preserve cortical cholinergic functions in these patients.

Keywords: Cognition; Early markers; Neuroimaging; Parkinson's disease; REM sleep Behavior disorder.