DOI 10.1007/s00702-004-0193-0 J Neural Transm (2005) 112: 231–237 Pergolide effect on cognitive functions in early-mild Parkinson’s disease L. Brusa 1;2 , P. Tiraboschi 4 , G. Koch 1;2 , A. Peppe 1 , M. Pierantozzi 2 , S. Ruggieri 3 , and P. Stanzione 1;2 1 IRCCS Fondazione S. Lucia, 2 Clinica Neurologica, Universita’degli Studi di Roma ‘‘Tor Vergata’’, and 3 Istituto di Clinica delle Malattie Nervose e Mentali, Universita’ di Roma ‘‘La Sapienza’’, Roma, and 4 Divisione Neurologia, Ospedale Niguarda Ca’Granda, Milano, Italy Received April, 2003; accepted June 26, 2004 Published online September 10, 2004; # Springer-Verlag 2004 Summary. In the present study, we evaluated the effect of pergolide, a mixed D1=D2 agonist, on cognitive function in mild Parkinson’s disease (PD). After a two-week wash-out phase, twenty patients with a Hoehn and Yahr score 2.5 entered a 16-week, cross-over study in which the order of administration of pergolide or 1-dopa was randomly assigned. Cognitive assessment was per- formed after the wash-out phase and repeated after eight weeks (before patients were switched to the other drug) and at the end of the study. There were no significant differences in test scores among the three experimental modalities (off-treatment vs. l-dopa, off-treatment vs. pergolide, pergolide vs. l-dopa). In another cohort of comparably mild PD patients we had previously demonstrated that pramipexole, a mixed D2=D3 agonist, slightly but signifi- cantly worsened verbal fluency in comparison to l-dopa; moreover, pramipexole impaired short term verbal memory and attentional-executive functions in com- parison to both l-dopa and the off-treatment condition. Taken together, these findings suggest that dopamine agonists may influence cognition in PD accord- ing to their pharmacological characteristics. Unlike the D2=D3 agonist prami- pexole, pergolide and l-dopa, both of which stimulate D1- and D2-receptor subtypes, do not appear to impair cognitive function. Keywords: Parkinson’s disease, cognition, pergolide. Introduction l-dopa is still the golden standard therapy in Parkinson’s disease (PD). However, many dopamine agonists are used in the clinical practice, although their influence on cognitive functions are controversial or not systematically