Links Identified Between Depression and Postural Instability in Early-Stage Parkinson Disease

Data from a cohort of nearly 100 patients with Parkinson disease suggest there are shared nondopaminergic pathogenic mechanisms between depression and postural instability symptoms of the disease.

Sun Ju Chung, MD, PhD, Department of Neurology, Asan Medical Center, University of Ulsan College, Seoul

Sun Ju Chung, MD, PhD

Recently published findings from a study of patients with early-stage Parkinson disease (PD) unexposed to antiparkinsonian drugs showed an association between depression and early occurrence of postural instability.1

Led by Sun Ju Chung, MD, PhD, Department of Neurology, Asan Medical Center, University of Ulsan College, Seoul, the investigators concluded that the data suggests that “shared nondopaminergic pathogenic mechanisms and potentially enables the prediction of early development of postural instability.” Additionally, they noted that depression should not be overlooked in this patient population, as it might suggest a more rapid development of these instabilities.

The trial featured 95 total patients with PD, 25 of which who were considered depressed and 70 nondepressed at baseline using the Geriatric Depression Scale (GDS). Participants had a mean age of 66.62 (±8.65) years at the onset of their symptoms, and were followed-up for a period of 53.40 (±16.79) months. To evaluate the effect of depression, investigators used 4 outcome variables: progression to Hoehn and Yahr (H-Y) stage 3, the occurrence of freezing of gat (FOG), levodopa-induced dyskinesia, and wearing-off.

At baseline, the initial motor scores showed a slightly different trend between the 2 groups (depressed: 14.16 [±4.88]; nondepressed: 11.81 [±5.22]; P = .052), with higher motor subscores for bradykinesia in the depressed PD group than in the nondepressed PD group (7.28 [±2.68] vs 5.61 [±2.69]; P = .0009). Overall, the GDS score was 22.48 (±2.86) points in the depressed group and 9.16 (±4.74) points in the nondepressed group (P <.001).

During the follow-up period, 51.6% (n = 49) of patients showed progression to H-Y stage 3, with higher proportions in the depressed group (68%) than those nondepressed (45.7%). After adjusting for associated variables, multivariate Cox proportional hazard analysis revealed that depression (hazard ratio [HR], 2.55; 95% CI, 1.32-4.93; P = .005), higher age at onset (HR, 1.05; 95% CI, 1.01-1.10; P = .0007), and frontal and executive dysfunction (HR, 2.09; 95% CI, 1.02-4.31; P = .045) were associated with progression to H-Y stage 3. Notably, a negative association was found between initial chief complex for tremor and progression to H-Y stage 3 (HR, 0.43; 95% CI, 0.22-0.82; P = .010).

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FOG developed in 5.3% (n = 5) of patients in the study, with more prominent occurrences in the depressed group (16.0%) than nondepressed (1.4%). On univariate analyses, patients wit depression (HR, 12.70; 95% CI, 1.42-113.89; P = .023) and higher levodopa equivalent daily dose (LEDD: HR, 1.003; 95% CI, 1.000-1.006; P = .024) might have associations with the occurrence of FOG; however, multivariate analyses found no significant associated factors.

The occurrence of levodopa-induced dyskinesia was similar between the groups, with 16.0% and 15.7% of depressed and nondepressed patients reporting the condition, respectively. Factors such as female sex (HR, 10.40; 95% CI, 1.25-86.77; P = .030), higher initial motor scores (HR, 1.17; 95% CI, 1.01-1.36; P = .043), and visuospatial dysfunction (HR, 3.86; 95% CI, 1.09-13.65; P = .036) were associated with the occurrence of levodopa-induced dyskinesia.

Wearing-off, which occurred in 28.0% of the depressed group and 18.6% of the nondepressed group, was not significantly different on Kaplan-Meier curve estimates (P = .351). Only higher age at onset was negatively associated with the occurrence of wearing-off after adjusting for associated variables (HR, 0.95; 95% CI, 0.90-1.00; P = .040). When using initial motor subscores, motor subscores for bradykinesia (HR, 1.38; 95% CI, 1.11-1.71; P = .004) and rigidity (HR, 0.60; 95% CI, 0.45-0.81; P = .001) were associated with the occurrence of wearing-off.

REFERENCE
1. Hwang YS, Jo Sungyang, Park KW, Lee SH, Lee S, Chung SJ. Association of depression with early occurrence of postural instability in Parkinson disease. J Mov Disord. Published online December 21, 2022. doi:10.14802/jmd.22091.
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