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. 2012 Aug;74(2):284-95.
doi: 10.1111/j.1365-2125.2012.04208.x.

Disease progress and response to treatment as predictors of survival, disability, cognitive impairment and depression in Parkinson's disease

Thuy C Vu  1 , John G Nutt, Nicholas H G Holford
Affiliations

Disease progress and response to treatment as predictors of survival, disability, cognitive impairment and depression in Parkinson's disease

Thuy C Vu et al. Br J Clin Pharmacol. 2012 Aug.

Abstract

Aim: To describe the time to clinical events (death, disability, cognitive impairment and depression) in Parkinson's disease using the time course of disease status and treatment as explanatory variables.

Methods: Disease status based on the Unified Parkinson's Disease Rating Scale (UPDRS) and the time to clinical outcome events were obtained from 800 patients who initially had early Parkinson's disease. Parametric hazard models were used to describe the time to the events of interest.

Results: Time course of disease status (severity) was an important predictor of clinical outcome events. There was an increased hazard ratio for death 1.4 (95% CI 1.31, 149), disability 2.75 (95% CI 2.30, 3.28), cognitive impairment 4.35 (95% CI 1.94, 9.74), and depressive state 1.43 (95% CI 1.26, 1.63) with each 10 unit increase of UPDRS. Age at study entry increased the hazard with hazard ratios of 49.1 (95% CI 8.7, 278) for death, 4.76 (95% CI 1.10, 20.6) for disability and 90.0 (95% CI 63.3-128) for cognitive impairment at age 60 years. Selegiline treatment had independent effects as a predictor of death at 8 year follow-up with a hazard ratio of 2.54 (95% CI 1.51, 4.25) but had beneficial effects on disability with a hazard ratio of 0.363 (95% CI 0.132, 0.533) and depression with a hazard ratio of 0.372 (95% CI 0.12, 0.552).

Conclusions: Our findings show that the time course of disease status based on UPDRS is a much better predictor of future clinical events than any baseline disease characteristic. Continued selegiline treatment appears to increase the hazard of death.

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Figures

Figure 1
Figure 1
Distribution of event times (in density scale) with a kernel density smooth (dashed lines)
Figure 2
Figure 2
Time course of hazard of death (EOT) for placebo (dashed line), levodopa 300 mg day−1 (solid line) and levodopa 300 mg day−1 plus selegiline 10 mg day−1 (dotted line)
Figure 3
Figure 3
Kaplan–Meier estimates of observed time to event data (solid lines) and associated 90% confidence intervals (dotted lines), overlaid with parametric model predictions of the base models (dashed lines) and their 90% confidence intervals (gray bands)
Figure 4
Figure 4
The time course of hazard of dropout for placebo (dashed line), levodopa 300 mg day−1 (solid line) and levodopa 300 mg day−1 plus selegiline 10 mg day−1 (dotted line)
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