The evolution of tremor in Parkinson's Disease: insights from a 4-year longitudinal assessment

Introduction: While tremor is considered a cardinal motor sign in patients with Parkinson’s disease (PD), little is known about the evolution of the different types of PD tremor over time. Aims: Our objectives were to assess the rate of progression of the various types of PD tremor over the disease course and to verify if the presence of different tremors is consistently associated with specific motor and non-motor burdens over time. Finally, we investigated whether the presence of different tremors can predict specific trajectories of disease progression. Methods: One hundred PD patients were enrolled and 73 completed a 4-year follow up. Clinical evaluations included the administration of standardized PD scales to assess the severity of motor and non-motor manifestations. The occurrence and severity of rest, re-emergent, and action tremors were accurately evaluated at baseline and 4 years later. Adjusted linear regression models were used to assess tremor type’s influence on disease progression. Results: Tremor occurrence and severity decreased during PD progression, with a more significant reduction in action tremor compared to rest and re-emergent tremor. Patients with rest and re-emergent tremor had milder motor symptoms at baseline and milder motor and non-motor manifestations at follow-up. The presence of rest and re-emergent tremor predicted a lower progression of non-motor symptoms. Conclusions: This longitudinal study revealed that the various types of PD tremor have different evolutions over disease course, can predict distinct trajectories of disease progression and are underpinned by distinct pathophysiological mechanisms.