The Clinical Profile of Tremor in Parkinson's Disease

BACKGROUND: Tremor is one of the most troublesome manifestations of Parkinson's Disease (PD) and its response to dopaminergic medication is variable; an evidence‐based framework of PD tremor is lacking yet needed to inform future investigations. OBJECTIVE: To perform a comprehensive longitudinal analysis on the clinical characteristics, course and response to dopaminergic medication of tremor in de‐novo PD. METHODS: Three hundred ninety‐seven participants were recruited in the Parkinson Progressive Markers Initiative, a prospective observational cohort study in early de‐novo PD. Rest, postural and kinetic tremor scores were extracted from the Movement Disorders Society—Unified Parkinson's Disease Rating Scale. Progression from baseline to 7‐year follow‐up of rest, postural and kinetic tremor scores, and their response to in‐clinic dopaminergic medication were analyzed through linear mixed‐effects models adjusted for age, sex and disease duration at enrollment. A sensitivity analysis was conducted through subgroup and imputation analyses. RESULTS: 382 (96.2%) participants showed tremor and 346 (87.2%) showed rest tremor in at least one assessment over 7 years. Off‐state rest, postural and kinetic tremor scores increased significantly over time, coupled with a significant effect of dopaminergic medication in reducing tremor scores. However, at each assessment, tremor was unresponsive to in‐clinic dopaminergic medication in at least 20% of participants for rest, 30% for postural and 38% for kinetic tremor. CONCLUSIONS: PD tremor is a troublesome manifestation, with increasing severity and variable response to medications. This analysis details the current clinical natural history of tremor in early‐to‐mid stage PD, outlining an evidence‐based framework for future pathophysiological and interventional studies.