Abstract
OBJECTIVE: To evaluate the course and predictors of neuropsychiatric symptoms (NPS) and cognition in patients with de novo Parkinson disease (PD). METHODS: Cross-sectional study of the cohort of de novo, untreated (at enrollment) patients with PD and healthy controls (HCs) from the Parkinson's Progression Markers Initiative. Participants have serial assessments of global cognition and symptoms of depression, anxiety, psychosis, impulse control disorders (ICDs), sleep and wakefulness, apathy, and fatigue. Available data up to 24 months of follow-up were included. RESULTS: The available sample size was as follows: baseline (PD = 423, HCs = 196), 12 months (PD = 261, HCs = 145), and 24 months (PD = 96, HCs = 83). Patients with PD experienced more depression, fatigue, apathy, and anxiety than HCs at all time points, and apathy (p = 0.001) and psychosis (p = 0.003) increased over time in patients with PD. Approximately two-thirds of patients with PD who screened positive for depression at any given visit were not taking an antidepressant. The Montreal Cognitive Assessment score decreased significantly over time in patients with PD (p < 0.001), but the change was comparable to that in HCs. At the 24-month visit, 44% of patients had been on dopamine replacement therapy (DRT) for at least 1 year, and this group reported more incident ICDs (p = 0.009) and excessive daytime sleepiness (p = 0.03). CONCLUSION: Multiple NPS are more common in de novo, untreated patients with PD compared with the general population, but they also remain relatively stable in early disease, while global cognition slightly deteriorates. In contrast, initiation of DRT is associated with increasing frequency of several other NPS.