Get access

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

Authors

  • Vikas Kotagal MD,

    Corresponding author
    1. Department of Neurology, University of Michigan, and Clinic Center, Veterans Administration Ann Arbor Health System
    • Department of Neurology, University of Michigan Medical School, 2301 Commonwealth Boulevard, Room 1013, Ann Arbor, MI 48105-2945
    Search for more papers by this author
  • Roger L. Albin MD,

    1. Department of Neurology, University of Michigan, and Clinic Center, Veterans Administration Ann Arbor Health System
    2. Neurology Service and Geriatric Research, Education, and Clinic Center, Veterans Administration Ann Arbor Health System
    Search for more papers by this author
  • Martijn L. T. M. Müller PhD,

    1. Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI
    Search for more papers by this author
  • Robert A. Koeppe PhD,

    1. Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI
    Search for more papers by this author
  • Ronald D. Chervin MD, MS,

    1. Department of Neurology, University of Michigan, and Clinic Center, Veterans Administration Ann Arbor Health System
    Search for more papers by this author
  • Kirk A. Frey MD, PhD,

    1. Department of Neurology, University of Michigan, and Clinic Center, Veterans Administration Ann Arbor Health System
    2. Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI
    Search for more papers by this author
  • Nicolaas I. Bohnen MD, PhD

    1. Department of Neurology, University of Michigan, and Clinic Center, Veterans Administration Ann Arbor Health System
    2. Neurology Service and Geriatric Research, Education, and Clinic Center, Veterans Administration Ann Arbor Health System
    3. Department of Radiology, Division of Nuclear Medicine, University of Michigan, Ann Arbor, MI
    Search for more papers by this author

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 [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;

Ancillary