Objective: aim of the study was to evaluate the dopamine binding characterizing subjects both at prodromal and symptomatic stages in α-synucleinopathies, by means of ROI-based and voxel-wise analyses.

Background: idiopathic REM sleep behavior disorder (iRBD) is the most specific feature associated with a high risk of developing α-synucleinopathy [1]. Dopaminergic Insula deficits play an important role in early phases of α-synucleinopathies, whereas no studies evaluated its alterations within the prodromal phases of the disease [2].

Method: in this multicenter study, individuals with polysomnography-confirmed iRBD (n=50), drug-naïve PD (n=100) and age-matched control (n=90) underwent a standardized neurological examination and dopaminergic imaging with ¹²³I-FP-CIT Brain SPECT. The between-groups differences in ¹²³I-FP-CIT insular and nigrostriatal binding were evaluated both with ROI-based and voxel-wise analyses – in age, sex, and center- adjusted models. Partial correlation analyses were performed to test the association between insular and nigrostriatal deficits and the relationship with motor and non-motor symptoms in prodromal and early stages of the disease.

Results: ROI-based and voxel-wise analyses showed an involvement of the insula in iRBD and PD compared to HC. RBD subjects were further classified in RBD-DAT- (n=36), and RBD-DAT+ (n=14) based on nigrostriatal binding. Both ROI and VBM analyses showed an early involvement of insula in RBD-DAT- with an additional impairment in nigrostriatal regions in RBD-DAT+ and PD. Bilateral insular uptake correlated with nigrostriatal uptake. Motor impairment in iRBD and PD was associated with lower nigrostriatal binding (i.e., putamen and pallidum) but not with insular uptake.

Conclusion: together, these results suggest insular dopaminergic deficits as core features of iRBD, even before the nigrostriatal deficits and motor impairment. Further longitudinal studies are warranted to evaluate the progression of insular dysfunction and potential compensation mechanisms in prodromal α-synucleinopathies.

References: [1] Postuma RB, Adler CH, Dugger BN, Hentz JG, Shill HA, Driver-Dunckley E, et al. REM sleep behavior disorder and neuropathology in Parkinson’s disease. Mov Disord 2015a; 30: 1413–7.

[2] Christopher, L., Koshimori, Y., Lang, A. E., Criaud, M., & Strafella, A. P. (2014). Uncovering the role of the insula in non-motor symptoms of Parkinson’s disease. Brain, 137(8), 2143-2154.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/insular-dopamine-deficits-in-prodromal-%ce%b1-synucleinopathies/