AbstractBackgroundEvidence regarding cortical atrophy patterns in Parkinson's disease (PD) with probable rapid eye movement sleep behavior disorder (RBD) (PD‐pRBD) remains scarce. Cortical mean diffusivity (cMD), as a novel imaging biomarker highly sensitive to detecting cortical microstructural changes in different neurodegenerative diseases, has not been investigated in PD‐pRBD yet.ObjectivesThe aim was to investigate cMD as a sensitive measure to identify subtle cortical microstructural changes in PD‐pRBD and its relationship with cortical thickness (CTh).MethodsTwenty‐two PD‐pRBD, 31 PD without probable RBD (PD‐nonpRBD), and 28 healthy controls (HC) were assessed using 3D T1‐weighted and diffusion‐weighted magnetic resonance imaging on a 3‐T scanner and neuropsychological testing. Measures of cortical brain changes were obtained through cMD and CTh. Two‐class group comparisons of a general linear model were performed (P < 0.05). Cohen's d effect size for both approaches was computed.ResultsPD‐pRBD patients showed higher cMD than PD‐nonpRBD patients in the left superior temporal, superior frontal, and precentral gyri, precuneus cortex, as well as in the right middle frontal and postcentral gyri and paracentral lobule (d > 0.8), whereas CTh did not detect significant differences. PD‐pRBD patients also showed increased bilateral posterior cMD in comparison with HCs (d > 0.8). These results partially overlapped with CTh results (0.5 < d < 0.8). PD‐nonpRBD patients showed no differences in cMD when compared with HCs but showed cortical thinning in the left fusiform gyrus and lateral occipital cortex bilaterally (d > 0.5).ConclusionscMD may be more sensitive than CTh displaying significant cortico‐structural differences between PD subgroups, indicating this imaging biomarker's utility in studying early cortical changes in PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.