title: Does levodopa accelerate the pathologic process in Parkinson disease brain?
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, UK.
authors.forename: L
authors.initials: L
authors.lastname: Parkkinen
authors.forename: S S
authors.initials: SS
authors.lastname: O'Sullivan
authors.forename: M
authors.initials: M
authors.lastname: Kuoppamäki
authors.forename: C
authors.initials: C
authors.lastname: Collins
authors.forename: C
authors.initials: C
authors.lastname: Kallis
authors.forename: J L
authors.initials: JL
authors.lastname: Holton
authors.forename: D R
authors.initials: DR
authors.lastname: Williams
authors.forename: T
authors.initials: T
authors.lastname: Revesz
authors.forename: A J
authors.initials: AJ
authors.lastname: Lees
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007980:Levodopa / Q000494:pharmacology* / Q000627:therapeutic use; D016631:Lewy Bodies / Q000187:drug effects / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D010300:Parkinson Disease / Q000188:drug therapy / Q000473:pathology*; D012720:Severity of Illness Index; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa