Morten Gersel Stokholm1, Alex Iranzo2, Karen Østergaard3, Mónica Serradell4, Marit Otto5, Kristina Bacher Svendsen3, Alicia Garrido6, Dolores Vilas6, Peter Parbo1, Per Borghammer1, Joan Santamaria2, Arne Møller1, Carles Gaig2, David J Brooks7, Eduardo Tolosa6, Nicola Pavese8. 1. Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Denmark. 2. Department of Neurology, Hospital Clínic de Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Hospital Clínic, IDIBAPS, Universitat de Barcelona, Catalonia, Spain; Multidisciplinary Sleep Unit, Hospital Clinic, Barcelona, Spain. 3. Department of Neurology, Aarhus University Hospital, Denmark. 4. Department of Neurology, Hospital Clínic de Barcelona, Spain; Multidisciplinary Sleep Unit, Hospital Clinic, Barcelona, Spain. 5. Department of Clinical Neurophysiology, Aarhus University Hospital, Denmark. 6. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Hospital Clínic, IDIBAPS, Universitat de Barcelona, Catalonia, Spain; Parkinson disease and Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Catalonia, Spain. 7. Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Denmark; Division of Neuroscience, Newcastle University, England, United Kingdom. 8. Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Denmark; Division of Neuroscience, Newcastle University, England, United Kingdom. Electronic address: npavese@cfin.au.dk.
Abstract
BACKGROUND: The majority of patients diagnosed with idiopathic rapid eye movement sleep behaviour disorder (iRBD) progress over time to a Lewy-type α-synucleinopathy such as Parkinson's disease or dementia with Lewy bodies. This in vivo molecular imaging study aimed to investigate if extrastriatal monoaminergic systems are affected in iRBD patients and if this coincides with neuroinflammation. METHODS: We studied twenty-one polysomnography-confirmed iRBD patients with 18F-DOPA and 11C-PK11195 positron emission tomography (PET) to investigate extrastriatal monoaminergic function and microglial activation. Twenty-nine healthy controls (n = 9 18F-DOPA and n = 20 11C-PK11195) were also investigated. Analyses were performed within predefined regions of interest and at voxel-level with Statistical Parametric Mapping. RESULTS: Regions of interest analysis detected monoaminergic dysfunction in iRBD thalamus with a 15% mean reduction of 18F-DOPA Ki values compared to controls (mean difference = -0.00026, 95% confidence interval [-0.00050 to -0.00002], p-value = 0.03). No associated thalamic changes in 11C-PK11195 binding were observed. Other regions sampled showed no 18F-DOPA or 11C-PK11195 PET differences between groups. Voxel-level interrogation of 11C-PK11195 binding identified areas with significantly increased binding within the occipital lobe of iRBD patients. CONCLUSION: Thalamic monoaminergic dysfunction in iRBD patients may reflect terminal dysfunction of projecting neurons from the locus coeruleus and dorsal raphe nucleus, two structures that regulate REM sleep and are known to be involved in the early phase of PD. The observation of significantly raised microglial activation in the occipital lobe of these patients might suggest early local Lewy-type α-synuclein pathology and possibly an increased risk for later cognitive dysfunction.
BACKGROUND: The majority of patients diagnosed with idiopathic rapid eye movement sleep behaviour disorder (iRBD) progress over time to a Lewy-type α-synucleinopathy such as Parkinson's disease or dementia with Lewy bodies. This in vivo molecular imaging study aimed to investigate if extrastriatal monoaminergic systems are affected in iRBD patients and if this coincides with neuroinflammation. METHODS: We studied twenty-one polysomnography-confirmed iRBD patients with 18F-DOPA and 11C-PK11195 positron emission tomography (PET) to investigate extrastriatal monoaminergic function and microglial activation. Twenty-nine healthy controls (n = 9 18F-DOPA and n = 20 11C-PK11195) were also investigated. Analyses were performed within predefined regions of interest and at voxel-level with Statistical Parametric Mapping. RESULTS: Regions of interest analysis detected monoaminergic dysfunction in iRBD thalamus with a 15% mean reduction of 18F-DOPA Ki values compared to controls (mean difference = -0.00026, 95% confidence interval [-0.00050 to -0.00002], p-value = 0.03). No associated thalamic changes in 11C-PK11195 binding were observed. Other regions sampled showed no 18F-DOPA or 11C-PK11195 PET differences between groups. Voxel-level interrogation of 11C-PK11195 binding identified areas with significantly increased binding within the occipital lobe of iRBD patients. CONCLUSION: Thalamic monoaminergic dysfunction in iRBD patients may reflect terminal dysfunction of projecting neurons from the locus coeruleus and dorsal raphe nucleus, two structures that regulate REM sleep and are known to be involved in the early phase of PD. The observation of significantly raised microglial activation in the occipital lobe of these patients might suggest early local Lewy-type α-synuclein pathology and possibly an increased risk for later cognitive dysfunction.
Authors: Elijah Mak; Ajenthan Surendranathan; Nicolas Nicastro; Franklin Aigbirhio; James Rowe; John O'Brien Journal: Mov Disord Clin Pract Date: 2018-11-08
Authors: Antonio P Strafella; Nico I Bohnen; Nicola Pavese; David E Vaillancourt; Thilo van Eimeren; Marios Politis; Alessandro Tessitore; Christine Ghadery; Simon Lewis Journal: Mov Disord Clin Pract Date: 2018-10-09
Authors: Ajenthan Surendranathan; Li Su; Elijah Mak; Luca Passamonti; Young T Hong; Robert Arnold; Patricia Vázquez Rodríguez; William R Bevan-Jones; Susannah A E Brain; Tim D Fryer; Franklin I Aigbirhio; James B Rowe; John T O'Brien Journal: Brain Date: 2018-12-01 Impact factor: 13.501