REM behavior disorder predicts motor progression and cognitive decline in Parkinson disease

Neurology. 2018 Sep 4;91(10):e894-e905. doi: 10.1212/WNL.0000000000006134. Epub 2018 Aug 8.

Abstract

Objective: To investigate whether REM sleep behavior disorder (RBD) is associated with worse motor and cognitive decline in Parkinson disease (PD) METHODS: Four-hundred twenty-one drug-naive patients with early-stage PD and 196 controls without PD were included in this study. All participants underwent a [123I]FP-CIT SPECT scan, CSF assessment, 3-tesla MRI, and thorough clinical assessments.

Results: At cross-sectional analyses, patients with PD and probable RBD (PD-RBD) had lower CSF β-amyloid 1-42 (Aβ42) levels and higher total tau to Aβ42 CSF ratio, higher nonmotor symptoms burden, and worse scores on neuropsychological tests of processing speed, visuospatial functioning, and delayed recognition memory compared to patients with PD without RBD. At longitudinal analyses, the presence of RBD was associated with faster motor progression (hazard ratio [HR] = 1.368, 95% confidence Interval [CI] = 1.036-1.806; p = 0.027) and cognitive decline (HR = 1.794, 95% CI = 1.163-2.768; p = 0.008) over 60-month follow-up. The presence of RBD was a predictor for motor progression only in patients with PD who had both low α-synuclein levels and low [123I]FP-CIT uptake in the striatum (HR = 2.091, 95% CI = 1.116-3.918; p = 0.021) and a predictor for cognitive decline only in patients with PD who had both low Aβ42 and low α-synuclein levels (HR = 2.810, 95% CI = 1.462-5.400; p = 0.002). In the population of controls without PD, the presence of RBD was not associated with cognitive decline or any baseline pathologic changes.

Conclusion: The presence of RBD in PD is associated with faster motor progression in patients with greater synuclein and dopaminergic pathology, and with higher risk of cognitive decline in patients with greater synuclein and amyloid pathology. Our findings provide an important direction toward understanding phenotypes and their prognosis in PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Brain / diagnostic imaging
  • Cognition Disorders / cerebrospinal fluid
  • Cognition Disorders / diagnosis*
  • Cognition Disorders / etiology*
  • Cohort Studies
  • Disease Progression
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Female
  • Humans
  • Imaging, Three-Dimensional
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Parkinson Disease / cerebrospinal fluid
  • Parkinson Disease / complications*
  • Parkinson Disease / diagnostic imaging
  • Parkinson Disease / epidemiology
  • Peptide Fragments / cerebrospinal fluid
  • REM Sleep Behavior Disorder / cerebrospinal fluid
  • REM Sleep Behavior Disorder / complications*
  • REM Sleep Behavior Disorder / diagnostic imaging
  • REM Sleep Behavior Disorder / epidemiology
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Tomography, Emission-Computed, Single-Photon
  • Tropanes / metabolism
  • alpha-Synuclein / cerebrospinal fluid
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Dopamine Plasma Membrane Transport Proteins
  • Peptide Fragments
  • Tropanes
  • alpha-Synuclein
  • amyloid beta-protein (1-42)
  • tau Proteins
  • 2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane