AbstractThe aim of this study is to determine whether structural MRI measures are associated with clinical impairment and progression to a Lewy body disease in patients with idiopathic REM sleep behavior disorder (iRBD). Twenty-seven patients with iRBD in addition to patients with de novo PD and healthy controls were included from the Parkinson’s Progression Markers Initiative. Patients with iRBD were followed for up to 3 years. Clinical and MRI measures were compared across groups and the association between clinical features and structural MRI was assessed in iRBD patients. Cox regression analyses were applied to identify risk factors for progressing to a Lewy body disease in iRBD. Our results showed that, at baseline, iRBD patients showed parietal and occipital cortical thinning, compared to controls. They also showed worse motor and non-motor abilities, some of which correlated with motor, frontal or temporal cortical thinning. At follow-up, six (22%) iRBD patients were diagnosed with a Lewy body disorder. These patients showed cortical thinning in frontal, occipital and parietal areas compared to iRBD non-converters. Cortical thinning was a significant predictor for future development of a Lewy body disorder (HR: 0.784; 95% CI: 0.640–0.960; p = 0.02). We conclude that cortical thinning is associated with worse motor and non-motor abilities, and predicts conversion to a Lewy body disorder in iRBD, suggesting it could be used to select candidates for clinical trials to delay the onset of neurodegenerative disease.