title: Symptoms of rapid eye movement sleep behavior disorder are associated with cholinergic denervation in Parkinson disease.
abstract: OBJECTIVE
  Rapid eye movement sleep behavior disorder (RBD) is common in Parkinson disease (PD), but its relationship to the varied neurotransmitter deficits of PD and prognostic significance remain incompletely understood. RBD and cholinergic system degeneration are identified independently as risk factors for cognitive impairment in PD. We aimed to assess the association between cholinergic denervation and symptoms of RBD in PD patients without dementia.
  
  
  METHODS
  Eighty subjects with PD without dementia (age, 64.6 ± 7.0 years; range, 50-82 years; 60 males, 20 females; mean Montreal Cognitive Assessment Test [MoCA] score, 26.2 ± 2.1; range 21-30) underwent clinical assessment, neuropsychological testing, and [(11)C]methylpiperidyl propionate acetylcholinesterase and [(11)C]dihydrotetrabenazine (DTBZ) vesicular monoamine transporter type 2 positron emission tomography (PET) imaging. (11)C3-Amino-4-(2-dimethylaminomethyl-phenylsulfaryl)-benzonitrile (DASB) serotonin transporter PET imaging was performed in a subset of 35 subjects. The presence of RBD symptoms was determined using the Mayo Sleep Questionnaire.
  
  
  RESULTS
  Twenty-seven of 80 subjects (33.8%) indicated a history of RBD symptoms. Subjects with and without RBD symptoms showed no significant differences in age, motor disease duration, MoCA, Unified Parkinson Disease Rating Scale motor scores, or striatal DTBZ binding. Subjects with RBD symptoms, in comparison to those without, exhibited decreased neocortical, limbic cortical, and thalamic cholinergic innervation (0.0213 ± 0.0018 vs 0.0236 ± 0.0022, t = 4.55, p < 0.0001; 0.0388 ± 0.0029 vs 0.0423 ± 0.0058, t = 2.85, p = 0.0056; 0.0388 ± 0.0025 vs 0.0427 ± 0.0042, t = 4.49, p < 0.0001, respectively). Brainstem and striatal DASB binding showed no significant differences between groups.
  
  
  CONCLUSIONS
  The presence of RBD symptoms in PD is associated with relative neocortical, limbic cortical, and thalamic cholinergic denervation although not with differential serotoninergic or nigrostriatal dopaminergic denervation. The presence of RBD symptoms may signal cholinergic system degeneration.
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, USA. vikaskot@med.umich.edu
authors.forename: Vikas
authors.initials: V
authors.lastname: Kotagal
authors.forename: Roger L
authors.initials: RL
authors.lastname: Albin
authors.forename: Martijn L T M
authors.initials: ML
authors.lastname: Müller
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koeppe
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Chervin
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Frey
authors.forename: Nicolaas I
authors.initials: NI
authors.lastname: Bohnen
mesh_terms: D000109:Acetylcholine / Q000032:analysis / Q000378:metabolism; D000368:Aged; D018678:Cholinergic Agents; D059329:Cholinergic Neurons / Q000000981:diagnostic imaging* / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography; D020187:REM Sleep Behavior Disorder / Q000000981:diagnostic imaging* / Q000209:etiology / Q000378:metabolism; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins / Q000032:analysis / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000032:analysis / Q000378:metabolism
chemical_list: D018678:Cholinergic Agents; D019275:Radiopharmaceuticals; C493452:SLC18A2 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D000109:Acetylcholine