Basal ganglia dysfunction in idiopathic REM sleep behaviour disorder parallels that in early Parkinson’s disease
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Published version
Accepted version
Author(s)
Type
Journal Article
Abstract
Resting-state fMRI (rs-fMRI) dysfunction within the basal ganglia network (BGN) is a feature of early Parkinson’s disease (Szewczyk-Krolikowski et al., 2014, Rolinski et al., 2015), and may be a diagnostic biomarker of basal ganglia dysfunction. Currently, it is unclear whether these changes are present in so-called idiopathic rapid eye movement sleep behaviour disorder (RBD), a condition associated with a high rate of future conversion to Parkinson’s. In this study, we explore the utility of rs-fMRI to detect BGN dysfunction in RBD. We compare these data to a set of healthy controls, and to a set of patients with established early Parkinson’s. Furthermore, we explore the relationship between rs-fMRI BGN dysfunction and loss of dopaminergic neurons assessed with dopamine transporter single photon emission computerised tomography (SPECT), and perform morphometric analyses to assess grey matter loss.
26 patients with polysomnographically established RBD, 48 Parkinson’s patients and 23 healthy controls were included in this study. Resting-state networks were isolated from task-free fMRI data using dual regression with a template was derived from a separate cohort of 80 elderly HC participants. Rs-fMRI parameter estimates were extracted from the study subjects in the BGN. In addition, 8 RBD, 10 Parkinson’s and 10 control subjects received 123I-ioflupane SPECT. We tested for reduction of BGN connectivity, and for loss of tracer uptake in RBD and Parkinson’s relative to each other and to controls.
Connectivity measures of BGN network dysfunction differentiated both RBD and Parkinson’s from controls with high sensitivity (96%) and specificity (74% for RBD, 78% for PD), indicating its potential as an indicator of early basal ganglia dysfunction. RBD was indistinguishable from Parkinson’s on rs-fMRI despite obvious differences on dopamine transported SPECT.
Basal ganglia connectivity is a promising biomarker for the detection of early BGN dysfunction, and may help to identify patients at risk of developing Parkinson’s in the future. Future risk stratification using a polymodal approach could combine BGN connectivity with clinical and other imaging measures, with important implications for future neuroprotective trials in RBD.
26 patients with polysomnographically established RBD, 48 Parkinson’s patients and 23 healthy controls were included in this study. Resting-state networks were isolated from task-free fMRI data using dual regression with a template was derived from a separate cohort of 80 elderly HC participants. Rs-fMRI parameter estimates were extracted from the study subjects in the BGN. In addition, 8 RBD, 10 Parkinson’s and 10 control subjects received 123I-ioflupane SPECT. We tested for reduction of BGN connectivity, and for loss of tracer uptake in RBD and Parkinson’s relative to each other and to controls.
Connectivity measures of BGN network dysfunction differentiated both RBD and Parkinson’s from controls with high sensitivity (96%) and specificity (74% for RBD, 78% for PD), indicating its potential as an indicator of early basal ganglia dysfunction. RBD was indistinguishable from Parkinson’s on rs-fMRI despite obvious differences on dopamine transported SPECT.
Basal ganglia connectivity is a promising biomarker for the detection of early BGN dysfunction, and may help to identify patients at risk of developing Parkinson’s in the future. Future risk stratification using a polymodal approach could combine BGN connectivity with clinical and other imaging measures, with important implications for future neuroprotective trials in RBD.
Date Issued
2016-08-01
Date Acceptance
2016-04-05
Citation
Brain, 2016, 139 (8), pp.2224-2234
ISSN
0006-8950
Publisher
Oxford University Press (OUP)
Start Page
2224
End Page
2234
Journal / Book Title
Brain
Volume
139
Issue
8
Copyright Statement
© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Sponsor
Michael J Fox Foundation
Grant Number
N/A
Subjects
Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences
Neurosciences & Neurology
Parkinson's disease
imaging
rapid eye movement sleep behaviour disorder
INDEPENDENT COMPONENT ANALYSIS
FUNCTIONAL CONNECTIVITY
EXECUTIVE DYSFUNCTION
NONMOTOR FEATURES
DELAYED EMERGENCE
EARLY MARKER
BRAIN
RISK
IMPAIRMENT
SYSTEM
Parkinson’s disease
imaging
rapid eye movement sleep behaviour disorder
Aged
Basal Ganglia Diseases
Female
Functional Neuroimaging
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Parkinson Disease
REM Sleep Behavior Disorder
Tomography, Emission-Computed, Single-Photon
Humans
Basal Ganglia Diseases
Parkinson Disease
REM Sleep Behavior Disorder
Tomography, Emission-Computed, Single-Photon
Magnetic Resonance Imaging
Aged
Middle Aged
Female
Male
Functional Neuroimaging
Neurology & Neurosurgery
11 Medical and Health Sciences
17 Psychology and Cognitive Sciences
Publication Status
Published
Date Publish Online
2016-06-12