Symptoms of rapid eye movement sleep behavior disorder are associated with cholinergic denervation in Parkinson disease

• Published in: Annals of neurology Vol. 71; no. 4; pp. 560 - 568
• Main Authors: Kotagal, Vikas, Albin, Roger L., Müller, Martijn L. T. M., Koeppe, Robert A., Chervin, Ronald D., Frey, Kirk A., Bohnen, Nicolaas I.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.04.2012; Wiley-Liss; Wiley Subscription Services, Inc
• Subjects: Acetylcholine - analysis; Acetylcholine - metabolism; Aged; Biological and medical sciences; Cholinergic Agents; Cholinergic Neurons - diagnostic imaging; Cholinergic Neurons - metabolism; Cross-Sectional Studies; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Humans; Male; Medical sciences; Middle Aged; Neurology; Neuropsychological Tests; Parkinson Disease - complications; Parkinson Disease - diagnostic imaging; Parkinson Disease - metabolism; Positron-Emission Tomography; Radiopharmaceuticals; REM Sleep Behavior Disorder - diagnostic imaging; REM Sleep Behavior Disorder - etiology; REM Sleep Behavior Disorder - metabolism; Serotonin Plasma Membrane Transport Proteins - analysis; Serotonin Plasma Membrane Transport Proteins - metabolism; Vesicular Monoamine Transport Proteins - analysis; Vesicular Monoamine Transport Proteins - metabolism; Nervous system diseases; Central nervous system disease; Parkinson disease; Degenerative disease; Sleep wake cycle; Behavior; Rapid eye movement sleep; Cerebral disorder; Extrapyramidal syndrome; Denervation
• ISSN: 0364-5134; 1531-8249; 1531-8249
• DOI: 10.1002/ana.22691

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 [11C]methylpiperidyl propionate acetylcholinesterase and [11C]dihydrotetrabenazine (DTBZ) vesicular monoamine transporter type 2 positron emission tomography (PET) imaging. 11C3‐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. Interpretation: 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. ANN NEUROL 2012;