Wider and Faster Degeneration of White Matter in Parkinson’s Disease with Possible REM Sleep Behaviour Disorder

Background In Parkinson's disease (PD), rapid eye movement (REM) sleep behaviour disorder (RBD) signifies a poorer prognosis, yet its impact on white matter (WM) degeneration remains unclear. The study examined the effect of RBD on WM alterations in PD progression. Methods The study included 45 PD patients with possible RBD (PD-pRBD), 38 PD patients without possible RBD (PD-npRBD), and 79 healthy controls (HC). All patients underwent clinical assessments and diffusion MRI scans at least once a year for up to 4 visits. 79 HC underwent the same protocol at baseline. WM metrics, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), were calculated using tract-based spatial statistics. Linear mixed-effects models were conducted to examine the changes in clinical features and WM fibers. Results At baseline, PD-npRBD showed increased RD in several regions, predominantly in bilateral uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF), compared to HC (PFDR<0.05). During follow-up, PD-npRBD had further FA decrease in left UF and ILF (PFDR<0.05). PD-pRBD showed reduced FA in several regions relative to HC at baseline (PFDR<0.05), and faster FA decline in left UF and ILF than PD-npRBD during follow-up, with more extensive FA decrease in other regions such as anterior thalamic radiation and inferior fronto-occipital fasciculus (PFDR<0.05). Moreover, increased RD in the left corticospinal tract correlated with motor symptoms (p=0.045) in PD-pRBD. Conclusions PD patients with pRBD demonstrated more extensive WM degeneration and accelerated degeneration in the left ILF and UF during the disease course. However, due to the lack of PSG verification, these results should be interpreted cautiously while directly relating to RBD. These findings provide new insights into the neural structural basis associated with the potential impact of RBD on PD progression.