Increased frontal [123I]FP-CIT binding in Parkinson’s disease patients with self-reported REM sleep behavior disorder

Abstract Rapid eye movement (REM) sleep behavior disorder (RBD) is a frequent non-motor symptom of Parkinson’s disease (PD) and a potential early marker of synucleinopathy-related neurodegeneration. While striatal dopaminergic dysfunction in PD-RBD has been extensively studied, the role of extrastri...

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Main Authors: Elina Jaakkola, Jani Ijas, Juho Joutsa, Tero Vahlberg, Elina Myller, Mikael Eklund, Simo Nuuttila, Kirsi Murtomäki, Tuomas Mertsalmi, Reeta Levo, Tommi Noponen, Toni Ihalainen, Filip Scheperjans, Valtteri Kaasinen
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:npj Parkinson's Disease
Online Access:https://doi.org/10.1038/s41531-025-01116-7
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author Elina Jaakkola
Jani Ijas
Juho Joutsa
Tero Vahlberg
Elina Myller
Mikael Eklund
Simo Nuuttila
Kirsi Murtomäki
Tuomas Mertsalmi
Reeta Levo
Tommi Noponen
Toni Ihalainen
Filip Scheperjans
Valtteri Kaasinen
author_facet Elina Jaakkola
Jani Ijas
Juho Joutsa
Tero Vahlberg
Elina Myller
Mikael Eklund
Simo Nuuttila
Kirsi Murtomäki
Tuomas Mertsalmi
Reeta Levo
Tommi Noponen
Toni Ihalainen
Filip Scheperjans
Valtteri Kaasinen
author_sort Elina Jaakkola
collection DOAJ
description Abstract Rapid eye movement (REM) sleep behavior disorder (RBD) is a frequent non-motor symptom of Parkinson’s disease (PD) and a potential early marker of synucleinopathy-related neurodegeneration. While striatal dopaminergic dysfunction in PD-RBD has been extensively studied, the role of extrastriatal monoaminergic alterations -particularly those involving serotonin - remains poorly understood. In this study, 155 PD patients underwent [123I]FP-CIT SPECT imaging to assess striatal and extrastriatal tracer binding, reflecting dopaminergic and broader monoaminergic function, respectively. Probable RBD was identified using a validated single-question screening tool with high sensitivity and specificity. Patients with probable RBD (RBD + , n = 44) were compared to those without (RBD − , n = 111) using voxel-wise and region-of-interest analyses, controlling for age, sex, disease duration, motor and non-motor symptom severity, and cognitive function. No significant differences were observed in striatal dopamine transporter binding. However, RBD+ patients showed significantly higher extrastriatal binding in the prefrontal cortex (pFWE < 0.05), suggesting a potential role for altered extrastriatal monoaminergic neurotransmission, possibly involving serotonergic pathways, in PD-RBD pathophysiology. These findings should be interpreted with caution due to the non-selective binding profile of the radiotracer.
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spelling doaj-art-0b4e52c13adb4173aa6445d704dbc8262025-08-20T03:42:23ZengNature Portfolionpj Parkinson's Disease2373-80572025-08-011111710.1038/s41531-025-01116-7Increased frontal [123I]FP-CIT binding in Parkinson’s disease patients with self-reported REM sleep behavior disorderElina Jaakkola0Jani Ijas1Juho Joutsa2Tero Vahlberg3Elina Myller4Mikael Eklund5Simo Nuuttila6Kirsi Murtomäki7Tuomas Mertsalmi8Reeta Levo9Tommi Noponen10Toni Ihalainen11Filip Scheperjans12Valtteri Kaasinen13Clinical Neurosciences, University of TurkuClinical Neurosciences, University of TurkuClinical Neurosciences, University of TurkuDepartment of Biostatistics, University of Turku and Turku University HospitalClinical Neurosciences, University of TurkuClinical Neurosciences, University of TurkuClinical Neurosciences, University of TurkuDepartment of Neurology, Helsinki University Hospital and Department of Clinical Neurosciences (Neurology), University of HelsinkiDepartment of Neurology, Helsinki University Hospital and Department of Clinical Neurosciences (Neurology), University of HelsinkiDepartment of Neurology, Helsinki University Hospital and Department of Clinical Neurosciences (Neurology), University of HelsinkiDepartment of Clinical Physiology, Nuclear Medicine, Turku PET Centre and Medical Physics, Turku University Hospital and Wellbeing services county of Southwest FinlandDepartment of Clinical Physiology and Nuclear Medicine, Helsinki University Hospital and University of HelsinkiDepartment of Neurology, Helsinki University Hospital and Department of Clinical Neurosciences (Neurology), University of HelsinkiClinical Neurosciences, University of TurkuAbstract Rapid eye movement (REM) sleep behavior disorder (RBD) is a frequent non-motor symptom of Parkinson’s disease (PD) and a potential early marker of synucleinopathy-related neurodegeneration. While striatal dopaminergic dysfunction in PD-RBD has been extensively studied, the role of extrastriatal monoaminergic alterations -particularly those involving serotonin - remains poorly understood. In this study, 155 PD patients underwent [123I]FP-CIT SPECT imaging to assess striatal and extrastriatal tracer binding, reflecting dopaminergic and broader monoaminergic function, respectively. Probable RBD was identified using a validated single-question screening tool with high sensitivity and specificity. Patients with probable RBD (RBD + , n = 44) were compared to those without (RBD − , n = 111) using voxel-wise and region-of-interest analyses, controlling for age, sex, disease duration, motor and non-motor symptom severity, and cognitive function. No significant differences were observed in striatal dopamine transporter binding. However, RBD+ patients showed significantly higher extrastriatal binding in the prefrontal cortex (pFWE < 0.05), suggesting a potential role for altered extrastriatal monoaminergic neurotransmission, possibly involving serotonergic pathways, in PD-RBD pathophysiology. These findings should be interpreted with caution due to the non-selective binding profile of the radiotracer.https://doi.org/10.1038/s41531-025-01116-7
spellingShingle Elina Jaakkola
Jani Ijas
Juho Joutsa
Tero Vahlberg
Elina Myller
Mikael Eklund
Simo Nuuttila
Kirsi Murtomäki
Tuomas Mertsalmi
Reeta Levo
Tommi Noponen
Toni Ihalainen
Filip Scheperjans
Valtteri Kaasinen
Increased frontal [123I]FP-CIT binding in Parkinson’s disease patients with self-reported REM sleep behavior disorder
npj Parkinson's Disease
title Increased frontal [123I]FP-CIT binding in Parkinson’s disease patients with self-reported REM sleep behavior disorder
title_full Increased frontal [123I]FP-CIT binding in Parkinson’s disease patients with self-reported REM sleep behavior disorder
title_fullStr Increased frontal [123I]FP-CIT binding in Parkinson’s disease patients with self-reported REM sleep behavior disorder
title_full_unstemmed Increased frontal [123I]FP-CIT binding in Parkinson’s disease patients with self-reported REM sleep behavior disorder
title_short Increased frontal [123I]FP-CIT binding in Parkinson’s disease patients with self-reported REM sleep behavior disorder
title_sort increased frontal 123i fp cit binding in parkinson s disease patients with self reported rem sleep behavior disorder
url https://doi.org/10.1038/s41531-025-01116-7
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