Dopamine and cognitive functioning in de novo subjects with Parkinson's disease: Effects of pramipexole and pergolide on working memory

• Published in: Neuropsychologia Vol. 47; no. 5; pp. 1374 - 1381
• Main Authors: Costa, Alberto, Peppe, Antonella, Dell’Agnello, Grazia, Caltagirone, Carlo, Carlesimo, Giovanni Augusto
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.04.2009; Elsevier
• Subjects: Adult and adolescent clinical studies; Attention - drug effects; Benzothiazoles - pharmacology; Benzothiazoles - therapeutic use; Biological and medical sciences; Cognition - drug effects; Cognitive functions; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopamine; Dopamine Agonists - pharmacology; Dopamine Agonists - therapeutic use; Female; Humans; Male; Medical sciences; Memory - drug effects; Middle Aged; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Neuropsychological Tests; Organic mental disorders. Neuropsychology; Parkinson Disease - drug therapy; Parkinson Disease - psychology; Parkinson's disease; Pergolide - pharmacology; Pergolide - therapeutic use; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Reaction Time - drug effects; Severity of Illness Index; Task Performance and Analysis; Working memory; Parkinson's disease; Dopamine; Working memory; Cognitive functions; Human; Agonist; Nervous system diseases; Parkinson disease; Ergot derivatives; Cognition; Neuroprotective agent; Catecholamine; Antiparkinson agent; Pramipexole; Cerebral disorder; Pergolide; D2 Dopamine receptor; Central nervous system disease; Dopamine agonist; Neurotransmitter; Degenerative disease; Extrapyramidal syndrome
• ISSN: 0028-3932; 1873-3514
• DOI: 10.1016/j.neuropsychologia.2009.01.039

Very few studies have investigated the relationship between dopaminergic therapy and working memory (WM) functioning in Parkinson's disease (PD) patients. The aim of the present study was to explore the effects of pharmacological treatment with pergolide (a D 1 + D 2 receptor agonist) and pramipexole (a D 2 + D 3 receptor agonist) on performance in visual–spatial, visual-object, and verbal WM tasks in PD patients. Participants included 19 “de novo” PD patients and 13 healthy controls (HC). The experimental task consisted of an n-back paradigm with verbal, visual-object, or visual–spatial stimuli. PD patients performed the task twice: after 18–24 h of therapy wash-out and after administration of pergolide (nine patients) or pramipexole (ten patients). HCs performed the task only once, without drug administration. Depending on how they performed in the “Off” and “On” therapy conditions, the nine PD patients each were classified into groups of low performers (i.e., performance on the n-back paradigm was below the median value of the experimental sample) and high performers (i.e., performance was above the median value). One PD patient was excluded from the analysis because his performance pattern clearly revealed that he was an outlier. In the low performer PD patients, administration of both pergolide and pramipexole improved accuracy on all WM tasks. No effect of the drugs was found in the high performer patients. The results of the present study show that stimulation of dopaminergic receptors improves high-level WM processes in PD patients, possibly by modulating activity in frontal–striatal circuits.