Development of anxiety in early Parkinson's disease: A clinical and biomarker study

Abstract

Background: Anxiety affects approximately 40% of Parkinson's disease (PD) patients. However, little is known about its predictors and development over time. Objective: To identify the clinical factors and biomarkers associated with development of anxiety in patients with newly diagnosed PD, and to test which risk factors predict increases in anxiety over time. Methods: Data from the Parkinson's Progression Markers Initiative (PPMI) were utilized. The primary outcome was the State–Trait Anxiety Inventory (STAI). Covariates were demographics, motor and non-motor symptoms, cognitive functions, dopamine transporter imaging data, and cerebrospinal fluid (CSF) biomarkers. We examined the association of risk factors at baseline and over 4 years with changes in anxiety scores over time. Results: A total of 252 patients met the inclusion criteria (mean age: 61.36 years, SD 9.53). At year 4, 42 patients had developed anxiety. Baseline predictors of increase in anxiety scores were greater autonomic dysfunction, dysexecutive function, CSF t-tau levels, excessive daytime sleepiness, and lower olfactory function scores but not motor scores. Over 4 years, change in anxiety scores correlated with deterioration in overall cognitive function, excessive daytime sleepiness, as well as depression and disability, and to a lesser degree worsening of Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor scores and caudate dopaminergic uptake changes. Conclusions: These findings suggest that development of anxiety in PD is not primarily based on a dopaminergic deficit in the basal ganglia but related to non-dopaminergic or extrastriatal pathology. Early dysexecutive function predicts development of anxiety but increase in anxiety levels correlates most strongly with more global cognitive decline.