Parkinson's Disease Non-Motor Subtypes Classification in a Group of Slovenian Patients: Actuarial vs. Data-Driven Approach

Background and purpose: The aim of this study was to examine the risk factors, prodromal symptoms, non-motor symptoms (NMS), and motor symptoms (MS) in different Parkinson's disease (PD) non-motor subtypes, classified using newly established criteria and a data-driven approach. Methods: A total of 168 patients with idiopathic PD underwent comprehensive NMS and MS examinations. NMS were assessed by the Non-Motor Symptom Scale (NMSS), Montreal Cognitive Assessment (MoCA), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ), Epworth Sleepiness Scale (ESS), Starkstein Apathy Scale (SAS) and Fatigue Severity Scale (FSS). Motor subtypes were classified based on Stebbins' method. Patients were classified into groups of three NMS subtypes (cortical, limbic, and brainstem) based on the newly designed inclusion criteria. Further, data-driven clustering was performed as an alternative, statistical learning-based classification approach. The two classification approaches were compared for consistency. Results: We identified 38 (22.6%) patients with the cortical subtype, 48 (28.6%) with the limbic, and 82 (48.8%) patients with the brainstem NMS PD subtype. Using a data-driven approach, we identified five different clusters. Three corresponded to the cortical, limbic, and brainstem subtypes, while the two additional clusters may have represented patients with early and advanced PD. Pearson chi-square test of independence revealed that a priori classification and cluster membership were significantly related to one another with a large effect size (chi(2)(8) = 175.001, p < 0.001, Cramer's V = 0.722). The demographic and clinical profiles differed between NMS subtypes and clusters. Conclusion: Using the actuarial and clustering approach, marked differences between individual NMS subtypes were found. The newly established criteria have potential as a simplified tool for future clinical research of NMS subtypes of Parkinson's disease.