Activity enhances dopaminergic long-duration response in Parkinson disease.

Abstract

OBJECTIVE
We tested the hypothesis that dopamine-dependent motor learning mechanism underlies the long-duration response to levodopa in Parkinson disease (PD) based on our studies in a mouse model. By data-mining the motor task performance in dominant and nondominant hands of the subjects in a double-blind randomized trial of levodopa therapy, the effects of activity and dopamine therapy were examined.
METHODS
We data-mined the Earlier versus Later Levodopa Therapy in Parkinson's Disease (ELLDOPA) study published in 2005 and performed statistical analysis comparing the effects of levodopa and dominance of handedness over 42 weeks.
RESULTS
The mean change in finger-tapping counts from baseline before the initiation of therapy to predose at 9 weeks and 40 weeks increased more in the dominant compared to nondominant hand in levodopa-treated subjects in a dose-dependent fashion. There was no significant difference in dominant vs nondominant hands in the placebo group. The short-duration response assessed by the difference of postdose performance compared to predose performance at the same visit did not show any significant difference between dominant vs nondominant hands.
CONCLUSIONS
Active use of the dominant hand and dopamine replacement therapy produces synergistic effect on long-lasting motor task performance during "off" medication state. Such effect was confined to dopamine-responsive symptoms and not seen in dopamine-resistant symptoms such as gait and balance. We propose that long-lasting motor learning facilitated by activity and dopamine is a form of disease modification that is often seen in trials of medications that have symptomatic effects.

Links

Publisher Full Text

Authors

Jung Kang U, Auinger P, Parkinson Study Group ELLDOPA Investigators, Mendis T

Institution

Department of Neurology, The University of Chicago, Chicago, IL, USA. unkang@uchicago.edu

Source

Neurology 78:15 2012 Apr 10 pg 1146-9

MeSH

Activities of Daily Living
Adult
Aged
Antiparkinson Agents
Dopamine Agents
Double-Blind Method
Drug Administration Schedule
Female
Functional Laterality
Humans
Levodopa
Male
Middle Aged
Parkinson Disease
Task Performance and Analysis

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22459675