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Progression of motor and nonmotor features of Parkinson's disease and their response to treatment.
Br J Clin Pharmacol. 2012 Aug; 74(2):267-83.BJ

Abstract

AIMS

(i) To describe the progression of the cardinal features of Parkinson's disease (PD); (ii) to investigate whether baseline PD subtypes explain disease progression; and (iii) to quantify the symptomatic and disease-modifying effects of anti-parkinsonian treatments.

METHODS

Data were available for 795 PD subjects, initially untreated, followed for up to 8 years. Cardinal features [tremor, rigidity, bradykinesia, and postural instability and gait disorder (PIGD)] were derived from the total unified Parkinson's disease rating scale (total UPDRS), cognitive status from the mini-mental status exam score (MMSE) and depression status from the Hamilton depression scale (HAM-D). Analysis was performed using a nonlinear mixed effects approach with an asymptotic model for natural disease progression. Treatment effects (i.e. symptomatic and disease modifying) were evaluated by describing changes in the natural history model parameters.

RESULTS

Tremor progressed more slowly (half-time of 3.9 years) than all other motor features (half-time 2-3 years). The MMSE progression was negligible, while HAM-D progressed with a half-time of 5 years. Levodopa had marked symptomatic effects on all features, but low potency for effect on PIGD (ED₅₀ of 1237 mg day⁻¹ compared with 7-24 mg day⁻¹ for other motor and nonmotor features). Other anti-parkinsonian treatments had much smaller symptomatic effects. All treatments had disease-modifying effects on the cardinal features of PD. Baseline PD subtypes only explained small differences in disease progression.

CONCLUSIONS

This analysis indicates that tremor progresses more slowly than other cardinal features and that PIGD is less treatment responsive in early PD patients. There was no evidence of baseline PD subtypes as a clinically useful predictor of disease progression rate. Anti-parkinsonian treatments have symptomatic and disease-modifying effects on all major features of PD.

Authors+Show Affiliations

Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Thousand Oaks, CA, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22283961

Citation

Vu, Thuy C., et al. "Progression of Motor and Nonmotor Features of Parkinson's Disease and Their Response to Treatment." British Journal of Clinical Pharmacology, vol. 74, no. 2, 2012, pp. 267-83.
Vu TC, Nutt JG, Holford NH. Progression of motor and nonmotor features of Parkinson's disease and their response to treatment. Br J Clin Pharmacol. 2012;74(2):267-83.
Vu, T. C., Nutt, J. G., & Holford, N. H. (2012). Progression of motor and nonmotor features of Parkinson's disease and their response to treatment. British Journal of Clinical Pharmacology, 74(2), 267-83. https://doi.org/10.1111/j.1365-2125.2012.04192.x
Vu TC, Nutt JG, Holford NH. Progression of Motor and Nonmotor Features of Parkinson's Disease and Their Response to Treatment. Br J Clin Pharmacol. 2012;74(2):267-83. PubMed PMID: 22283961.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Progression of motor and nonmotor features of Parkinson's disease and their response to treatment. AU - Vu,Thuy C, AU - Nutt,John G, AU - Holford,Nicholas H G, PY - 2012/1/31/entrez PY - 2012/1/31/pubmed PY - 2012/11/14/medline SP - 267 EP - 83 JF - British journal of clinical pharmacology JO - Br J Clin Pharmacol VL - 74 IS - 2 N2 - AIMS: (i) To describe the progression of the cardinal features of Parkinson's disease (PD); (ii) to investigate whether baseline PD subtypes explain disease progression; and (iii) to quantify the symptomatic and disease-modifying effects of anti-parkinsonian treatments. METHODS: Data were available for 795 PD subjects, initially untreated, followed for up to 8 years. Cardinal features [tremor, rigidity, bradykinesia, and postural instability and gait disorder (PIGD)] were derived from the total unified Parkinson's disease rating scale (total UPDRS), cognitive status from the mini-mental status exam score (MMSE) and depression status from the Hamilton depression scale (HAM-D). Analysis was performed using a nonlinear mixed effects approach with an asymptotic model for natural disease progression. Treatment effects (i.e. symptomatic and disease modifying) were evaluated by describing changes in the natural history model parameters. RESULTS: Tremor progressed more slowly (half-time of 3.9 years) than all other motor features (half-time 2-3 years). The MMSE progression was negligible, while HAM-D progressed with a half-time of 5 years. Levodopa had marked symptomatic effects on all features, but low potency for effect on PIGD (ED₅₀ of 1237 mg day⁻¹ compared with 7-24 mg day⁻¹ for other motor and nonmotor features). Other anti-parkinsonian treatments had much smaller symptomatic effects. All treatments had disease-modifying effects on the cardinal features of PD. Baseline PD subtypes only explained small differences in disease progression. CONCLUSIONS: This analysis indicates that tremor progresses more slowly than other cardinal features and that PIGD is less treatment responsive in early PD patients. There was no evidence of baseline PD subtypes as a clinically useful predictor of disease progression rate. Anti-parkinsonian treatments have symptomatic and disease-modifying effects on all major features of PD. SN - 1365-2125 UR - https://www.unboundmedicine.com/medline/citation/22283961/Progression_of_motor_and_nonmotor_features_of_Parkinson's_disease_and_their_response_to_treatment_ L2 - https://doi.org/10.1111/j.1365-2125.2012.04192.x DB - PRIME DP - Unbound Medicine ER -