Objective: The aim of this study was to test if markers of the brain-first Parkinson’s disease (PD) subtype are associated with a greater or more asymmetric reduction of gray matter volume (GMV) in comparison to the body-first subtype.

Background: A new hypothesis of alpha-synuclein spread in PD distinguishes between two subtypes based on the initial site of the pathology: brain-first and body-first. In comparison to body-first, brain-first PD is conceptually associated with an earlier and more asymmetric involvement of the central nervous system (e.g., more asymmetric loss of dopamine transporters) and the relative absence of REM-sleep-behavioral-disorder (RBD).

Method: Data of 255 PD patients were retrieved from a database (ppmi-info.org). Dopamine transporter asymmetry index (AI) of the putamen and RBD status of the RBDSQ were used as markers. GMVs and their asymmetry were obtained of each Braak stage.

Results: PD patients generally showed Braak-stage-dependent reduction of GMVs. However, putaminal AI was not significantly correlated with the GMV asymmetry in any Braak stage. Additionally, putaminal AI was also not significantly correlated with the GMV volume of the more affected side in any Braak stage. In comparison to RBD+, RBD- patients did not show a significantly smaller GMV volume of the more affected side in any Braak stage and the GMV asymmetry did also not significantly differ between groups.

Conclusion: Our findings indicate that greater asymmetry in dopaminergic denervation or lack of RBD is not associated with earlier or more asymmetric degeneration of cerebral Braak stages. Therefore, this study fails to provide evidence in support of the brain-first/body-first spreading hypothesis.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/gray-matter-volume-of-proposed-brain-first-and-body-first-parkinsons-disease-subtypes/