Decoding Prodromal Parkinson's Disease: Clinical Differences between Isolated Hyposmia and REM Sleep Behavior Disorder

Abstract Background The prodromal phase of Parkinson’s disease (PD), much like the disease itself, displays marked heterogeneity, with varied rates of progression and symptom severities. A detailed clinical characterization of prodromal subgroups may provide useful insights for both clinical and research settings. Objectives To compare clinical assessments in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) and those with isolated hyposmia. Methods A cross-sectional study was conducted on 191 patients with iRBD, 213 patients with isolated hyposmia and 150 healthy controls recruited in the Parkinson’s Progression Markers Initiative. The earliest available assessment for each participant was selected. Our analysis investigated and compared the Montreal Cognitive Assessment, Scales for Outcomes in Parkinson’s Disease Autonomic Dysfunction (SCOPA-AUT) and Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts I, II and III scores across the three groups. To assess differences, after adjusting for age and sex, we employed permutations testing. We further investigated the specific question items that contributed most significantly to the observed variations between the groups. Results We found significant differences between the healthy control group and a combined prodromal group across all assessment categories, with prodromal participants displaying poorer scores. For between prodromal groups comparison, significant differences emerged in SCOPA-AUT and MDS-UPDRS Part I scores, with the iRBD group presenting with more severe scores. Conclusion Our study highlights that even in the premotor stage of PD, clinical distinctions exist in terms of autonomic burden between individuals with iRBD and those with isolated hyposmia.