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

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 t...

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Bibliographic Details
Published in:British journal of clinical pharmacology 2012-08, Vol.74 (2), p.284-295
Main Authors: Vu, Thuy C., Nutt, John G., Holford, Nicholas H. G.
Format: Article
Language:English
Subjects:
Adult
Adult and adolescent clinical studies
Aged
Analysis of Variance
Antiparkinson Agents - therapeutic use
Biological and medical sciences
Chi-Square Distribution
Cognition - drug effects
Cognition Disorders - diagnosis
Cognition Disorders - drug therapy
Cognition Disorders - etiology
Cognition Disorders - mortality
Cognition Disorders - psychology
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Depression
Depression - diagnosis
Depression - drug therapy
Depression - etiology
Depression - mortality
Depression - psychology
Disability Evaluation
disease progress
Disease Progression
Humans
Intellectual deficiency
Kaplan-Meier Estimate
levodopa
Medical sciences
Middle Aged
Mood disorders
Neurology
Parkinson Disease - complications
Parkinson Disease - diagnosis
Parkinson Disease - drug therapy
Parkinson Disease - mortality
Parkinson Disease - physiopathology
Parkinson Disease - psychology
Parkinson's disease
Patient Dropouts
Pharmacology. Drug treatments
Predictive Value of Tests
Psychiatric Status Rating Scales
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Randomized Controlled Trials as Topic
Retrospective Studies
Risk Assessment
Risk Factors
selegiline
Selegiline - therapeutic use
Severity of Illness Index
Time Factors
time to event
time‐dependent covariate
Tocopherols - therapeutic use
Treatment of Parkinson's disease
Treatment Outcome
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Summary: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.
ISSN:0306-5251
1365-2125
DOI:10.1111/j.1365-2125.2012.04208.x