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

Authors

  • Thuy C. Vu,

    1. Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Thousand Oaks, CA
    Search for more papers by this author
  • John G. Nutt,

    1. Department of Neurology, Oregon Health and Science University, Portland, OR, USA
    Search for more papers by this author
  • Nicholas H. G. Holford

    Corresponding author
    1. Department of Pharmacology and Clinical Pharmacology, University of Auckland, New Zealand
      Professor Nick Holford MBChB FRACP, Department Pharmacology & Clinical Pharmacology, University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand. Tel.: +64 (9) 923 6730. Fax: +64 (9) 373 7090. E-mail: n.holford@auckland.ac.nz
    Search for more papers by this author

Professor Nick Holford MBChB FRACP, Department Pharmacology & Clinical Pharmacology, University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand. Tel.: +64 (9) 923 6730. Fax: +64 (9) 373 7090. E-mail: n.holford@auckland.ac.nz

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The marked between variability in the rate of progression of Parkinson's disease severity assessed with a global functional score (Unified Parkinson' Disease Rating Scale, UPDRS) is recognized but its origin is uncertain and variously attributed to different subtypes of Parkinson's disease, life style, genetic variability and treatment. An increased risk of death in patients treated with selegiline has been reported but this is controversial.

WHAT THIS STUDY ADDS

• We used a hazard model approach to describe the time to clinical events (death, disability, depression and dementia). The time course of disease status changes was shown to be a key predictor of the risk of these events. Baseline motor subtype was not a predictor of outcome events. Selegiline was associated with an increased risk of death that was independent of its effect on disease status.

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.

Ancillary