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

Parkinsonism Relat Disord. 2020 Dec:81:89-93. doi: 10.1016/j.parkreldis.2020.10.014. Epub 2020 Oct 8.


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 (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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Aged
  • Carbon Radioisotopes
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / metabolism*
  • Cholinesterase Inhibitors
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / metabolism
  • Donepezil
  • Female
  • Humans
  • Inflammation / metabolism*
  • Isoquinolines
  • Male
  • Mental Status and Dementia Tests
  • Microglia / metabolism*
  • Middle Aged
  • Positron-Emission Tomography
  • REM Sleep Behavior Disorder / diagnostic imaging
  • REM Sleep Behavior Disorder / metabolism*
  • Substantia Innominata / diagnostic imaging
  • Substantia Innominata / metabolism*


  • Carbon Radioisotopes
  • Carbon-11
  • Cholinesterase Inhibitors
  • Isoquinolines
  • Donepezil
  • Acetylcholinesterase
  • PK 11195