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Abstract
Background: Several in vitro studies have suggested levodopa (l-dopa) to be toxic to dopaminergic neurons and that it can modulate the aggregation process of α-synuclein. We investigated the relationship between cumulative lifetime dose of l-dopa and nigral neuronal count and Lewy body (LB) pathology in Parkinson disease (PD).
Methods: Density of pigmented neurons was measured unilaterally in a single section of substantia nigra (SN) with delineation of the dorsal and ventral tiers in 96 cases of PD with well-documented clinical records relating to antiparkinsonian drug treatment. Cortical and nigral LB densities were determined using a morphometric approach.
Results: Mean lifetime dose of l-dopa correlated significantly (p < 0.001) with duration of PD in the entire study population (n = 96) and it was not possible to disentangle their individual effect. This was not the case in a subgroup analysis of younger onset patients with a longer duration of PD (n = 40) who showed no significant correlation between l-dopa and total SN neuronal density (p = 0.07), after adjustment for duration of illness. There was, however, a lower neuronal density in the ventral (p = 0.02) but not in the dorsal (p = 0.27) tier detected with the cumulative dose of l-dopa. We found no difference in l-dopa dose between Braak PD stages (p = 0.58). Furthermore, the subgroup analysis showed no relationship of l-dopa dose to either cortical (p = 0.47) or nigral (p = 0.48) LB density.
Conclusion: Chronic use of l-dopa in PD does not enhance progression of PD pathology as far as can be determined by our observations with SN neuronal counts and LB densities.
GLOSSARY
- CI=
- confidence interval;
- DAQ=
- dopamine-quinones;
- ERR=
- estimated relative rate;
- ICC=
- intraclass correlation coefficient;
- LB=
- Lewy body;
- PD=
- Parkinson disease;
- QSBB=
- Queen Square Brain Bank;
- SN=
- substantia nigra.
Footnotes
Study funding: This work was undertaken at UCLH/UCL, which received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme. The Queen Square Brain Bank for Neurological Disorders is supported by the Reta Lila Weston Trust, the Progressive Supranuclear Palsy (Europe) Association, the Multiple System Atrophy, and the Alzheimer's Research Trust.
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Supplemental data at www.neurology.org
- Received October 27, 2010.
- Accepted March 10, 2011.
- Copyright © 2011 by AAN Enterprises, Inc.
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Letters: Rapid online correspondence
- How to study Levodopa Toxicity
- Levodopa probably does not accelerate parkinsonian pathology in substantia nigra neurons since it does not involve the basic pathophysiological process which causes the disease, which is most likely neuorinflammation in microglia
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