TY - JOUR
T1 - Impaired metabolic brain networks associated with neurotransmission systems in the α-synuclein spectrum
AU - Carli, Giulia
AU - Caminiti, Silvia Paola
AU - Sala, Arianna
AU - Galbiati, Andrea
AU - Pilotto, Andrea
AU - Ferini-Strambi, Luigi
AU - Padovani, Alessandro
AU - Perani, Daniela
N1 - Funding Information:
This study was supported by CARIPLO Project “Evaluation of autonomic, genetic, imaging and biochemical markers for Parkinson-related dementia: longitudinal assessment of a PD cohort” 2016–2020 (grant agreement no. 2014-0832 )” (D.P.).
Publisher Copyright:
© 2020 Elsevier Ltd
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - Introduction: While the involvement of multiple neurotransmitter systems in α-synucleinopathies is reported, a comprehensive study on their metabolic connectivity reconfiguration in the preclinical and clinical disease-spectrum is lacking. We aimed to investigate shared and disease-specific neural vulnerabilities of the nigro-striato-cortical dopaminergic, noradrenergic and cholinergic networks within the α-synuclein-spectrum, by means of metabolic connectivity approach. Methods: We collected 34 polysomnography-confirmed isolated REM sleep behaviour disorder (iRBD) subjects, 29 idiopathic Parkinson's disease (PD) patients without dementia, 30 patients with probable dementia with Lewy bodies (DLB), and 50 healthy controls for comparisons. Neurotransmission networks' analyses were performed through multivariate partial correlations based on FDG-PET brain metabolic data. Results: We found: a) the nigro-striato-cortical dopaminergic network with a limited reconfiguration in individuals with iRBD, but moderate-to-severe alterations in patients with DLB and PD; b) an extended connectivity alteration of the noradrenergic network in all groups; c) changes within the cholinergic networks connectivity in the whole disease-spectrum, with some differences: PD with only moderate connectivity reconfiguration and DLB with the most severe alterations, some of these shared with iRBD. Conclusions: Synucleinopathies can be considered multisystem disorders, with common and disease-specific neurotransmission networks reconfigurations. The present findings indicate dopaminergic connectivity alterations only when associated with parkinsonism, a very early involvement of noradrenergic networks, occurring in both the iRBD and in symptomatic PD/DLB patients and cholinergic alterations with disease-specific vulnerabilities shared by iRBD and DLB. The latter finding may represent an early biomarker of disease progression to dementia.
AB - Introduction: While the involvement of multiple neurotransmitter systems in α-synucleinopathies is reported, a comprehensive study on their metabolic connectivity reconfiguration in the preclinical and clinical disease-spectrum is lacking. We aimed to investigate shared and disease-specific neural vulnerabilities of the nigro-striato-cortical dopaminergic, noradrenergic and cholinergic networks within the α-synuclein-spectrum, by means of metabolic connectivity approach. Methods: We collected 34 polysomnography-confirmed isolated REM sleep behaviour disorder (iRBD) subjects, 29 idiopathic Parkinson's disease (PD) patients without dementia, 30 patients with probable dementia with Lewy bodies (DLB), and 50 healthy controls for comparisons. Neurotransmission networks' analyses were performed through multivariate partial correlations based on FDG-PET brain metabolic data. Results: We found: a) the nigro-striato-cortical dopaminergic network with a limited reconfiguration in individuals with iRBD, but moderate-to-severe alterations in patients with DLB and PD; b) an extended connectivity alteration of the noradrenergic network in all groups; c) changes within the cholinergic networks connectivity in the whole disease-spectrum, with some differences: PD with only moderate connectivity reconfiguration and DLB with the most severe alterations, some of these shared with iRBD. Conclusions: Synucleinopathies can be considered multisystem disorders, with common and disease-specific neurotransmission networks reconfigurations. The present findings indicate dopaminergic connectivity alterations only when associated with parkinsonism, a very early involvement of noradrenergic networks, occurring in both the iRBD and in symptomatic PD/DLB patients and cholinergic alterations with disease-specific vulnerabilities shared by iRBD and DLB. The latter finding may represent an early biomarker of disease progression to dementia.
KW - Brain metabolic connectivity
KW - Graph theory
KW - Neurotransmission
KW - α-synuclein-spectrum
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U2 - 10.1016/j.parkreldis.2020.10.036
DO - 10.1016/j.parkreldis.2020.10.036
M3 - Article
C2 - 33120072
AN - SCOPUS:85093930026
VL - 81
SP - 113
EP - 122
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
SN - 1353-8020
ER -