ACUTE EFFECTS OF LEVODOPA ON NEUROPSYCHOLOGICAL PERFORMANCE IN STABLEAND FLUCTUATING PARKINSONS-DISEASE PATIENTS AT DIFFERENT LEVODOPA PLASMA-LEVELS

The contribution of dopaminergic systems to cognitive defects in Parki nson's disease and the cognitive effects of levodopa remain controvers ial. The levodopa plasma levels and the neuropsychological performance of 10 parkinsonian patients with a stable motor response to the drug, and IO matched parkinsonian patients with a 'wearing-off' phenomenon were studied 12 h after levodopa was withdrawn (time zero), and at 1 h and 4 h after an oral dose of levodopa (i.e. at '+1H' and '+4H'), to investigate whether discrete cognitive domains are more sensitive to l evodopa in parkinsonian patients with the wearing-off-phenomenon. Cons idering the 20 patients as a whole, levodopa significantly,diminished the response time in verbal and visuospatial memory tests, the extra-d imensional matching test and the Wisconsin card sorting test (WCST), w ithout significantly improving or worsening the patient's accuracy. A significant group-by-time effect was only evident in the WCST while in stable patients levodopa produced no changes, wearing-off patients si gnificantly reduced the number of categories achieved and had more per severative errors at +1H, recovering at +4H. These results confirm pre vious findings of selective adverse effects of levodopa on highly dema nding executive tasks in Parkinson's disease and additionally suggest that some previous discrepancies between studies may be accounted for by lack of differentiation between stable and wearing-off conditions. 'Frontal' disturbances on neuropsychological tests with levodopa may b ecome evident only after massive degeneration of the dopamine systems has occurred.