Abstract

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are thought to be part of a spectrum: both have a clinical profile including symptoms associated with dopaminergic and serotonergic loss, yet few imaging studies have focused on serotonergic neurodegeneration in both disorders. We aimed to study degeneration of terminals with dopamine and serotonin transporter (DAT and SERT, respectively) in patients with early-stage PD and DLB relative to healthy controls, using 123 I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ( 123 I-FP-CIT) single photon emission computed tomography (SPECT). We conducted region of interest (ROI) and voxel-based analyses on 123 I-FP-CIT SPECT scans. Using the cerebellum as a reference region, we determined binding ratios (BRs) for bilateral ROIs in the DAT-rich striatum (head of the caudate nucleus and posterior putamen) and SERT-rich extrastriatal brain regions (thalamus, hypothalamus and hippocampus). We compared BRs in PD and DLB patients with BRs in healthy controls (all groups: n = 16). Both PD and DLB patients had lower striatal 123 I-FP-CIT BRs than healthy controls for the bilateral caudate head (PD—left: F(1,29) = 28.778, P <.001, ω 2 = 0.35; right: F(1,29) = 35.338, P <.001, ω 2 = 0.42; DLB—left: F(1,29) = 28.241, P <.001, ω 2 = 0.31; right: F(1,29) = 18.811, P <.001, ω 2 = 0.26) and bilateral posterior putamen (PD—left: F(1,29) = 107.531, P <.001, ω 2 = 0.77; right: F(1,29) = 87.525, P <.001, ω 2 = 0.72; DLB—left: F(1,29) = 39.910, P <.001, ω 2 = 0.48; right: F(1,29) = 26.882, P <.001, ω 2 = 0.38). DLB patients had lower hypothalamic 123 I-FP-CIT BRs than healthy controls (F(1,29) = 6.059, P =.020, ω 2 = 0.12). In the voxel-based analysis, PD and DLB patients had significantly lower striatal binding than healthy controls. Both PD patients in the early disease stages and DLB patients have reduced availability of striatal DAT, and DLB patients lower hypothalamic SERT compared with healthy controls. These observations add to the growing body of evidence that PD and DLB are not merely dopaminergic diseases, thereby providing additional clinicopathological insights.
Original languageEnglish
Article number101755
JournalNeuroImage: Clinical
Volume22
Early online date12 Mar 2019
DOIs
Publication statusPublished - 2019

Cite this

@article{4714fea1304c408483d391cac36c52e6,
title = "Striatal DAT and extrastriatal SERT binding in early-stage Parkinson's disease and dementia with Lewy bodies, compared with healthy controls: An 123I-FP-CIT SPECT study",
abstract = "Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are thought to be part of a spectrum: both have a clinical profile including symptoms associated with dopaminergic and serotonergic loss, yet few imaging studies have focused on serotonergic neurodegeneration in both disorders. We aimed to study degeneration of terminals with dopamine and serotonin transporter (DAT and SERT, respectively) in patients with early-stage PD and DLB relative to healthy controls, using 123 I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ( 123 I-FP-CIT) single photon emission computed tomography (SPECT). We conducted region of interest (ROI) and voxel-based analyses on 123 I-FP-CIT SPECT scans. Using the cerebellum as a reference region, we determined binding ratios (BRs) for bilateral ROIs in the DAT-rich striatum (head of the caudate nucleus and posterior putamen) and SERT-rich extrastriatal brain regions (thalamus, hypothalamus and hippocampus). We compared BRs in PD and DLB patients with BRs in healthy controls (all groups: n = 16). Both PD and DLB patients had lower striatal 123 I-FP-CIT BRs than healthy controls for the bilateral caudate head (PD—left: F(1,29) = 28.778, P <.001, ω 2 = 0.35; right: F(1,29) = 35.338, P <.001, ω 2 = 0.42; DLB—left: F(1,29) = 28.241, P <.001, ω 2 = 0.31; right: F(1,29) = 18.811, P <.001, ω 2 = 0.26) and bilateral posterior putamen (PD—left: F(1,29) = 107.531, P <.001, ω 2 = 0.77; right: F(1,29) = 87.525, P <.001, ω 2 = 0.72; DLB—left: F(1,29) = 39.910, P <.001, ω 2 = 0.48; right: F(1,29) = 26.882, P <.001, ω 2 = 0.38). DLB patients had lower hypothalamic 123 I-FP-CIT BRs than healthy controls (F(1,29) = 6.059, P =.020, ω 2 = 0.12). In the voxel-based analysis, PD and DLB patients had significantly lower striatal binding than healthy controls. Both PD patients in the early disease stages and DLB patients have reduced availability of striatal DAT, and DLB patients lower hypothalamic SERT compared with healthy controls. These observations add to the growing body of evidence that PD and DLB are not merely dopaminergic diseases, thereby providing additional clinicopathological insights.",
keywords = "Parkinson Disease, Lewy body dementia, SPECT, Dopamine transporter, imaging, Serotonin, brain, serotonin transporter, control group, STRIATUM, hypothalamus",
author = "Merijn Joling and Chris Vriend and Raijmakers, {Pieter G. H. M.} and {van der Zande}, {Jessica J.} and Lemstra, {Afina W.} and Berendse, {Henk W.} and Jan Booij and {van den Heuvel}, {Odile A.}",
note = "Copyright {\circledC} 2019 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2019",
doi = "10.1016/j.nicl.2019.101755",
language = "English",
volume = "22",
journal = "NeuroImage: Clinical",
issn = "2213-1582",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Striatal DAT and extrastriatal SERT binding in early-stage Parkinson's disease and dementia with Lewy bodies, compared with healthy controls

T2 - An 123I-FP-CIT SPECT study

AU - Joling, Merijn

AU - Vriend, Chris

AU - Raijmakers, Pieter G. H. M.

AU - van der Zande, Jessica J.

AU - Lemstra, Afina W.

AU - Berendse, Henk W.

AU - Booij, Jan

AU - van den Heuvel, Odile A.

N1 - Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2019

Y1 - 2019

N2 - Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are thought to be part of a spectrum: both have a clinical profile including symptoms associated with dopaminergic and serotonergic loss, yet few imaging studies have focused on serotonergic neurodegeneration in both disorders. We aimed to study degeneration of terminals with dopamine and serotonin transporter (DAT and SERT, respectively) in patients with early-stage PD and DLB relative to healthy controls, using 123 I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ( 123 I-FP-CIT) single photon emission computed tomography (SPECT). We conducted region of interest (ROI) and voxel-based analyses on 123 I-FP-CIT SPECT scans. Using the cerebellum as a reference region, we determined binding ratios (BRs) for bilateral ROIs in the DAT-rich striatum (head of the caudate nucleus and posterior putamen) and SERT-rich extrastriatal brain regions (thalamus, hypothalamus and hippocampus). We compared BRs in PD and DLB patients with BRs in healthy controls (all groups: n = 16). Both PD and DLB patients had lower striatal 123 I-FP-CIT BRs than healthy controls for the bilateral caudate head (PD—left: F(1,29) = 28.778, P <.001, ω 2 = 0.35; right: F(1,29) = 35.338, P <.001, ω 2 = 0.42; DLB—left: F(1,29) = 28.241, P <.001, ω 2 = 0.31; right: F(1,29) = 18.811, P <.001, ω 2 = 0.26) and bilateral posterior putamen (PD—left: F(1,29) = 107.531, P <.001, ω 2 = 0.77; right: F(1,29) = 87.525, P <.001, ω 2 = 0.72; DLB—left: F(1,29) = 39.910, P <.001, ω 2 = 0.48; right: F(1,29) = 26.882, P <.001, ω 2 = 0.38). DLB patients had lower hypothalamic 123 I-FP-CIT BRs than healthy controls (F(1,29) = 6.059, P =.020, ω 2 = 0.12). In the voxel-based analysis, PD and DLB patients had significantly lower striatal binding than healthy controls. Both PD patients in the early disease stages and DLB patients have reduced availability of striatal DAT, and DLB patients lower hypothalamic SERT compared with healthy controls. These observations add to the growing body of evidence that PD and DLB are not merely dopaminergic diseases, thereby providing additional clinicopathological insights.

AB - Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are thought to be part of a spectrum: both have a clinical profile including symptoms associated with dopaminergic and serotonergic loss, yet few imaging studies have focused on serotonergic neurodegeneration in both disorders. We aimed to study degeneration of terminals with dopamine and serotonin transporter (DAT and SERT, respectively) in patients with early-stage PD and DLB relative to healthy controls, using 123 I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ( 123 I-FP-CIT) single photon emission computed tomography (SPECT). We conducted region of interest (ROI) and voxel-based analyses on 123 I-FP-CIT SPECT scans. Using the cerebellum as a reference region, we determined binding ratios (BRs) for bilateral ROIs in the DAT-rich striatum (head of the caudate nucleus and posterior putamen) and SERT-rich extrastriatal brain regions (thalamus, hypothalamus and hippocampus). We compared BRs in PD and DLB patients with BRs in healthy controls (all groups: n = 16). Both PD and DLB patients had lower striatal 123 I-FP-CIT BRs than healthy controls for the bilateral caudate head (PD—left: F(1,29) = 28.778, P <.001, ω 2 = 0.35; right: F(1,29) = 35.338, P <.001, ω 2 = 0.42; DLB—left: F(1,29) = 28.241, P <.001, ω 2 = 0.31; right: F(1,29) = 18.811, P <.001, ω 2 = 0.26) and bilateral posterior putamen (PD—left: F(1,29) = 107.531, P <.001, ω 2 = 0.77; right: F(1,29) = 87.525, P <.001, ω 2 = 0.72; DLB—left: F(1,29) = 39.910, P <.001, ω 2 = 0.48; right: F(1,29) = 26.882, P <.001, ω 2 = 0.38). DLB patients had lower hypothalamic 123 I-FP-CIT BRs than healthy controls (F(1,29) = 6.059, P =.020, ω 2 = 0.12). In the voxel-based analysis, PD and DLB patients had significantly lower striatal binding than healthy controls. Both PD patients in the early disease stages and DLB patients have reduced availability of striatal DAT, and DLB patients lower hypothalamic SERT compared with healthy controls. These observations add to the growing body of evidence that PD and DLB are not merely dopaminergic diseases, thereby providing additional clinicopathological insights.

KW - Parkinson Disease

KW - Lewy body dementia

KW - SPECT

KW - Dopamine transporter

KW - imaging

KW - Serotonin

KW - brain

KW - serotonin transporter

KW - control group

KW - STRIATUM

KW - hypothalamus

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85062858119&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/30884365

U2 - 10.1016/j.nicl.2019.101755

DO - 10.1016/j.nicl.2019.101755

M3 - Article

VL - 22

JO - NeuroImage: Clinical

JF - NeuroImage: Clinical

SN - 2213-1582

M1 - 101755

ER -