The diagnosis of Parkinson’s disease (PD) is based on motor dysfunctions and, at early stages, responsiveness to dopamine replacement treatment. However, PD patients also suffer from many non-motor functions of which cognitive impairments are common, but difficult to treat. Apart from having a large impact on the patients’ quality of life, cognitive symptoms can develop into overt dementia, a debilitating disease state which is the strongest predictor of the need for nursing home placement. Since cognitive symptoms are present even at an early stage of PD when lesions mainly involve the nigrostriatal dopaminergic pathway, these symptoms are likely to be related to subcortical pathology. Changes in interactions between nigrostriatal dopaminergic neurons and other neurotransmitter systems, and subsequent effects both within and outside the basal ganglia, are associated with cognitive symptoms of PD. Using novel transgenic models combined with relevant behavioral and biochemical assessments to study the molecular mechanisms underlying cognitive processing, my project aims at deciphering the pathophysiology underlying cognitive dysfunction in PD and to unravel potential procognitive therapeutic strategies.