Changes in Action Tremor in Parkinson's Disease over Time: Clinical and Neuroimaging Correlates

Background: The various symptoms of Parkinson's disease (PD) may change differently over time as the disease progresses. Tremor usually manifests early in the disease, but unlike other motor symptoms, its severity may diminish over time. The cerebral mechanisms underlying these symptom-specific longitudinal trajectories are unclear. Previous magnetic resonance imaging (MRI) studies have shown structural changes in brain regions associated with PD tremor, suggesting that structural changes over time may define clinical trajectories.

Objectives: The aims were to investigate the longitudinal trajectory of PD tremor in relation to bradykinesia and rigidity, and assess whether tremor progression is related to structural changes in tremor-related areas.

Methods: We used data from the Personalized Parkinson Project: a two-year longitudinal study involving 520 PD patients and 60 healthy controls, who were measured twice clinically and with MRI. Mixed-effects models were used to compare tremor, bradykinesia, and rigidity progression; investigate gray matter changes in tremor-related regions (cerebello-thalamo-cortical circuit and pallidum); and calculate associations between symptom severity and brain structure. Associations across the whole brain were included to assess anatomical specificity.

Results: Bradykinesia and rigidity worsened over 2 years, whereas tremor behaved differently: resting tremor severity remained stable, whereas postural and kinetic tremor severity decreased. Attenuation of postural and kinetic tremor was associated with, but not restricted to, atrophy in tremor-related areas. Opposite relationships were observed for bradykinesia and rigidity.

Conclusions: Action tremor (postural and kinetic) is an early symptom of PD, which reduces with disease progression. Longitudinal brain atrophy correlates with tremor and other motor symptoms in opposite ways. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.