Two distinct trajectories of clinical and neurodegeneration events identified in Parkinson's disease

Abstract

Background Increasing evidence suggests that Parkinson's disease (PD) may have distinct spatial and temporal progression patterns. We aimed to disentangle the distinct trajectories of clinical and neurodegeneration events of PD by using a novel data-driven Subtype and Stage Inference (SuStaIn) model.Methods We enrolled 201 PD patients and 118 healthy controls with comprehensive olfactory, autonomic function, cognitive, sleep, emotional tests, and multimodality MRI scanning (T1-weighted imaging, diffusion tensor imaging, and neuromelanin-sensitive imaging). The volume and mean diffusivity of cortical/subcortical regions, the signal of substantia nigra (SN) and locus coeruleus (LC) were then obtained. Above features were input into SuStaIn model to identify PD subtypes with distinct progress trajectories. An independent dataset with 151 PD patients and 57 healthy controls was used to validate our findings. Finally, the differences in clinical, imaging, biochemical profiles, levodopa treatment response, and longitudinal prognosis between PD subtypes were assessed. Results We identified two distinct PD subtypes: subtype 1 with rapid eye movement sleep behavior disorder (RBD), autonomic dysfunction, SN and LC degeneration as early manifestations and cognitive impairment, limbic degeneration as advanced manifestation; while subtype 2 with cognitive impairment, SN and limbic degeneration as early manifestation, and RBD, LC degeneration as advanced manifestations. The two subtypes were successfully validated in the independent dataset. In addition, we found that subtype 1 showed poorer levodopa response and longitudinal prognosis when compared with subtype 2.Conclusion We demonstrated two PD subtypes with distinct clinical and neurodegeneration trajectories, which are consistent with the recently proposed “body-first” and “brain-first” hypothesis. Meanwhile, the distinct treatment response and prognosis between two subtypes provided new insights into the underlying disease biology and may be useful for personalized treatment for individuals with different subtypes of PD.

Assessing the Role of Locus Coeruleus Degeneration in Essential Tremor and Parkinson’s Disease with Sleep Disorders

“…1). The methods for outlining the SN were described in our study [25]. The mean and standard deviation (SD) of the SI were calculated for LC, SN, PT, and cerebral peduncle (CP).…”