Non-motor subtypes in candidates for subthalamic deep brain stimulation for Parkinson's disease

Abstract

Introduction: Patients with Parkinson's Disease (PD) vary markedly in terms of non-motor symptoms (NMS) as the disease progresses. To improve PD management and clinical-trial assessment, we aimed to determine NMS endotypes in a cohort of patients with advanced PD.

Methods: We conducted an ancillary cluster analysis of the 2013-2018 cohort (n = 722) of PREDISTIM. In this French multicenter interventional cohort, consecutive candidates for subthalamic deep brain stimulation undergo thorough assessment of motor symptoms (MS) and NMS at the inclusion visit. The NMS data are based on the MDS-UPDRS, Montreal Cognitive Assessment (MoCA), and several psychiatric scales: Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D), and Lille Apathy Rating Scale (LARS). Cluster analysis with 17 NMS was conducted to identify groups with homogenous NMS profiles.

Results: Three distinct NMS clusters were identified. The largest had mild MS. The smallest had moderate MS and the most severe NMS, including cognitive and psychiatric dysfunction. The middle-large group had moderate MS and NMS but was distinguished by having the worst sleeping problems. The clusters did not differ in onset age or patient age and may be underpinned by disparate patterns of anatomical brain damage.

Conclusion: The mainly-motor (Cluster 1), mainly non-motor (Cluster 3), and intermediate (Cluster 2) NMS endophenotypes must be replicated in an independent cohort but may help stratify patients for management (pharmacological, deep-brain stimulation, and non-pharmacological treatments) and inclusion and assessment in clinical trials.

Keywords: MDS-UPDRS; Non-motor symptoms; PREDISTIM; Parkinson's disease endophenotypes; Prognosis.