Dopaminergic modulation of cognitive function-implications for L-DOPA treatment in Parkinson's disease.
It is well recognised that patients with Parkinson's disease exhibit cognitive deficits, even in the earliest disease stages. Whereas, L-DOPA therapy in early Parkinson's disease is accepted to improve the motor symptoms, the effects on cognitive performance are more complex: both positive and negative effects have been observed. The purpose of the present article is to review the effects of L-DOPA medication in Parkinson's disease on cognitive functions in the broad domains of cognitive flexibility and working memory. The review places the effects in Parkinson's disease within a framework of evidence from studies with healthy human volunteers, rodents and non-human primates as well as computational modeling work. It is suggested that beneficial or detrimental effects of L-DOPA are observed depending on task demands and basal dopamine levels in distinct parts of the striatum. The study of the beneficial and detrimental cognitive effects of L-DOPA in Parkinson's disease has substantial implications for the understanding and treatment development of cognitive abnormalities in Parkinson's disease as well as normal health.
Cools
Roshan
R
Helen Wills Neuroscience Institute, University of California, 132 Barker Hall, Berkeley, USA. roshanco@berkeley.edu
D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000627:therapeutic use*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology
D000978:Antiparkinson Agents; D007980:Levodopa; D004298:Dopamine