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

Lookup NU author(s): Professor David BrooksORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


© The AuthorsIntroduction: 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 (BPND) 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 BPND 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.

Publication metadata

Author(s): Staer K, Iranzo A, Stokholm MG, Ostergaard K, Serradell M, Otto M, Svendsen KB, Garrido A, Vilas D, Santamaria J, Moller A, Gaig C, Brooks DJ, Borghammer P, Tolosa E, Pavese N

Publication type: Article

Publication status: Published

Journal: Parkinsonism and Related Disorders

Year: 2020

Volume: 81

Pages: 89-93

Print publication date: 01/12/2020

Online publication date: 08/10/2020

Acceptance date: 06/10/2020

Date deposited: 21/10/2021

ISSN (print): 1353-8020

ISSN (electronic): 1873-5126

Publisher: Elsevier Ltd


DOI: 10.1016/j.parkreldis.2020.10.014


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