Tract-Based Spatial Statistics Reveal Lower White Matter Integrity Specific to Idiopathic Rapid Eye Movement Sleep Behavior Disorder as a Proxy for Prodromal Parkinson’s Disease

Abstract

BACKGROUND: Parkinson's disease (PD) is characterized by distinct motor symptoms which do not manifest until significant neurodegeneration has already occurred. Therefore, preventative treatments depend on PD being detected in a prodromal phase. To date, prodromal PD (pPD) has been conceptualized based on conditions such as REM Sleep Behavior Disorder (RBD), which has a high conversion rate to clinical PD (cPD). However, few studies have examined microstructural differences between healthy controls (HC), pPD, and cPD. OBJECTIVE: The current study examined white matter microstructure in different phases of PD progression. METHODS: Participants included 21 HC, 20 pPD (14 with RBD and 6 with hyposmia), and 17 cPD from the Parkinson's Progression Markers Initiative database. Tract-based spatial statistics were used to determine between group differences in fractional anisotropy (FA) and mean diffusivity (MD). RESULTS: Mean diffusivity was significantly increased in pPD relative to cPD in widespread, but mostly right lateralized regions. Post-hoc analyses indicated that this pattern was particular to individuals with RBD. There were no microstructural differences between HC and pPD or cPD. The pPD group had significantly higher RBD symptoms and the cPD group had significantly higher motor symptoms. CONCLUSIONS: Observed microstructural deterioration in individuals with RBD relative to cPD may indicate an altered pattern of neurodegeneration associated with RBD as a prodromal symptom of PD. Future studies should aim to further characterize possible differential patterns of progression from various non-motor symptoms (e.g., RBD, hyposmia) to cPD using longitudinal designs.