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While iRBD shows emerging brain changes, their impact on structural connectivity and network efficiency, and their predictive value, remain poorly characterized.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>In this international prospective study, 198 polysomnography\u2010confirmed iRBD patients and 174 controls underwent diffusion magnetic resonance imaging and were analyzed. Cutting\u2010edge diffusion tractography and network\u2010based statistics were applied to reconstruct individual connectomes and assess network properties predicting DLB or PD.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Structural architecture was already disrupted in iRBD, with both reduced and compensatory increased connections. Global efficiency was decreased. Local efficiency in motor regions was altered and associated with early clinical symptoms. Altered local efficiency in the supramarginal gyrus predicted DLB only.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Early disruption of brain architecture in iRBD predicts progression to synucleinopathy\u2010related dementia, offering a novel potential prognostic biomarker.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Isolated rapid eye movement sleep behavior disorder (iRBD) patients show significant alterations in inter\u2010regional structural connectivity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Global efficiency is reduced in iRBD compared to controls.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Areas with increased local efficiency contribute to decreased global efficiency.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Altered network efficiency is associated with emerging Parkinsonian 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