Pathophysiological understanding of the pre-clinical or early prodromal stages of PD are essential for the development of new therapeutic strategies. Parkinson’s disease (PD) commences several years before the onset of motor features. The latter finding may represent an early biomarker of disease progression to dementia. 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 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.Ĭonclusions: Synucleinopathies can be considered multisystem disorders, with common and disease-specific neurotransmission networks reconfigurations. 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 Through multivariate partial correlations based on FDG-PET brain metabolic data. Neurotransmission networks’ analyses were performed 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. We aimed to investigate shared and disease-specific neural vulnerabilities of the nigrostriato-cortical dopaminergic, noradrenergic and cholinergic networks within the α-synuclein-spectrum, by means of metabolic connectivity approach. 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.
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