Disease progress and response to treatment as predictors of survival, disability, cognitive impairment and depression in Parkinson's disease.
OBJECTIVE
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.
Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Thousand Oaks, CA, USA.
Thuy C
TC
Vu
John G
JG
Nutt
Nicholas H G
NH
Holford
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality / Q000523:psychology; D003863:Depression / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality / Q000523:psychology; D004185:Disability Evaluation; D018450:Disease Progression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology / Q000523:psychology; D010352:Patient Dropouts; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012642:Selegiline / Q000627:therapeutic use; D012720:Severity of Illness Index; D013997:Time Factors; D024505:Tocopherols / Q000627:therapeutic use; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D012642:Selegiline; D024505:Tocopherols