Association of Baseline Depression and Anxiety with Longitudinal Health Outcomes in Parkinson's Disease

Abstract

Background: Anxiety and depression are common non-motor symptoms in Parkinson's disease (PD) but remain under-recognized and under-treated.

Objectives: To evaluate functional outcomes associated with baseline anxiety or depression and effects related to the initiation of new psychiatric treatment.

Methods: We analyzed 7 years of data from patients with de novo PD enrolled in the Parkinson's Progression Markers Initiative. Longitudinal regression models evaluated the association between baseline anxiety and depression with Schwab and England (SE) and MDS-UPDRS total scores over time. Cox proportional hazard models assessed effects of baseline anxiety and depression on time to initiation of dopaminergic therapy. Piecewise linear regression models examined the association of treatment initiation for anxiety and depression with SE and MDS-UPDRS.

Results: 490 participants with baseline depression and anxiety data were included. Anxiety and depression were associated with lower SE (anxiety: β = -1.31, P = 0.038, depression: β = -1.96, P = 0.012, co-morbid: β = -2.70, P = 0.003) and higher MDS-UPDRS scores (anxiety: β = 5.37, P < 0.001, depression: β = 9.17, P < 0.001, co-morbid: β = 10.50, P < 0.001) longitudinally. Anxiety was associated with faster time to dopamine replacement therapy initiation (HR 1.30, 95% CI 1.03-1.66, P = 0.03). 16 participants with anxiety initiated treatment for anxiety, which was associated with subsequent lower levodopa daily dose (slope change = -218.49, P = 0.018). 10 participants with depression initiated treatment of depression, which was associated with reduced MDS-UPDRS total scores (slope change = -8.3, P < 0.001) and higher SE scores (slope change = 5.99, P = 0.004).

Conclusions: Anxiety and depression at PD onset are associated with multiple negative longitudinal trajectories. However, preliminary findings suggest that anxiety and depression treatment may be linked with improved motor and non-motor outcomes.

Keywords: PPMI; Parkinson's disease; anxiety and depression; neuropsychiatric symptoms.

Figure 1

Schwab and England and total unified Parkinson's disease ration scale (UPDRS) scores over time for participants as a function of baseline neuropsychiatric symptom status.

Figure 2

Cox proportional hazards models of time to start of dopamine replacement therapy (DRT) for anxiety and depression.

Figure 3

Trajectory of total unified Parkinson disease ration scale (UPDRS) scores and levodopa equivalent dose (LEDD) for individual participants with initially untreated depression and anxiety who were later treated. A vertical line marks the inflection point at time 0 indicating the start of treatment for individuals in each cohort.