Objective: We hypothesised that changes in the brain structure and connectivity would be present at this stage.

Background: There is wide consensus that prolonged prodromal phase precedes the onset of motor symptoms in Parkinson’s disease (PD).

Method: We included T1- and DTI-MRI data of 21 prodromal subjects, with anosmia or idiopathic Rapid Eye Movement Sleep Behaviour Disorder (RBD), to assess structural changes in grey (GM) and white matter (WM) in comparison with 60 age- and gender- matched healthy controls. Voxel-based morphometry (VBM) was used to quantify GM changes and tract-based spatial statistics to quantify WM fractional anisotropy (FA) and mean diffusivity (MD).

Results: Prodromal PD subjects had greater RBD symptoms and olfactory dysfunction, and greater global non-motor burden (MDS-UPDRS I) and autonomic dysfunction (SCOPA-AUT) compared to healthy controls (P<0.05). Prodromal subjects showed structural and microstructural changes in the hypothalamus, with decreased VBM-GM (P<0.05) and WM-FA (P<0.001), and increased WM-MD values (P<0.001). Lower VBM-GM in the hypothalamus correlated with greater non-motor burden (r=-0.664, P=0.004) and autonomic dysfunction (r=-0.740, P=0.001). Prodromal PD patients also showed increased WM-MD in the substantia nigra (P<0.001), globus pallidus (P<0.05) and ventral striatum (P<0.05) and increased WM-FA in the substantia nigra (P<0.001), thalamus (P<0.001), and putamen (P<0.001) compared to healthy controls.

Conclusion: Prodromal PD patients possess a unique set of structural and microstructural volumetric alterations that distinguish them from healthy subjects. Our findings demonstrate that MRI changes are present in the premotor stages of PD. This abstract was also submitted for presentation at the 2019 European Academy of Neurology conference.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/structural-connectivity-changes-in-prodromal-parkinsons-disease-patients-a-multimodal-mri-study/