Apathy and Anxiety in De Novo Parkinson's Disease Predict the Severity of Motor Complications

Background: Neuropsychiatric and affective symptoms are prevalent in prodromal and clinical Parkinson's disease (PD). Some evidence suggests that they may also signify risk for motor complications (motor fluctuations and dyskinesias) of dopamine replacement therapy (DRT). Objective: To determine whether neuropsychiatric symptoms present in de novo PD (ie, before DRT initiation) predict the severity of eventual motor complications of DRT. Methods: We used clinical, demographic, neurobehavioral, and neuroimaging data from the Parkinson's Progression Markers Initiative (PPMI), a multicenter observational PD study. Participants were unmedicated at enrollment and 361 initiated DRT during PPMI follow-up. We used Cox proportional hazard and multivariate ordinal mixed-effects regression models to evaluate the relationship between baseline neuropsychiatric symptoms and motor complications as measured by the Movement Disorders Society-revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Results: The cumulative incidences of dyskinesias and motor fluctuations during follow-up (6.0 ± 1.5 years) were 34.3% and 59.9%, respectively. Both apathy and high trait-anxiety (top quartile) conveyed over two-fold increases in hazard for dyskinesia onset and for adverse impact on activities of daily living caused by both dyskinesias and motor fluctuations. The longitudinal severity of motor fluctuations and dyskinesias was significantly predicted by baseline trait-anxiety and apathy, but not depression. Models were adjusted for dimensionally related symptoms (eg autonomic dysfunction) and potential confounding variables (eg DRT dose). Conclusions: Apathy and anxiety levels in de novo PD may be neuropsychiatric biomarkers of vulnerability to earlier and more disabling motor complications of DRT.