Altered Network Efficiency in Isolated REM Sleep Behaviour Disorder: A Multicentric Study

Isolated REM sleep behavior disorder (iRBD), a prodromal synucleinopathy, generally precedes Parkinson’s disease (PD) or dementia with Lewy bodies (DLB). While disruptions in structural brain connectivity have been reported in these diseases, their presence in prodromal phases such as iRBD remains unclear. In this cross-sectional study, we analysed diffusion MRI in a large multicentric dataset (198 iRBD, 174 controls), mapping white matter pathways between 462 regions. Comparing groups, we found disrupted structural connectivity in iRBD. This included reduced density in multiple cortical areas alongside focal increases suggesting compensation in parietal, orbitofrontal and visual cortices. Global and local efficiency were altered in iRBD, notably in motor-related regions (putamen, thalamus, sensorimotor and parietal cortices), and was associated with emerging motor features. Importantly, increased local efficiency in the supramarginal gyrus predicted phenoconversion to DLB, but not PD. These findings highlight early structural connectivity disruptions in iRBD, offering a potential marker for progression to DLB.