Relationship of Dopamine to Cognitive Function in Parkinson's Disease

Parkinson's disease (PD) is a common neurodegenerative disorder, particularly in the elderly population. PD is characterized primarily by motor impairment, but cognitive impairment is common and dementia may occur in about 30% of patients. The pathological hallmark of PD is the selective degeneration of nigrostriatal dopamine neurons and the appearance of intracytoplasmic inclusions known as Lewy Bodies. Dopaminergic dysfunction has been widely demonstrated in PD patients. Reductions in \[18F\]FDOPA uptake has been consistently observed in PD, although it remains to be established whether there are relative differences between PD with and without dementia, and its association with cognitive function. Furthermore, data relating to dopamine D1 receptors in PD are limited to post mortem studies and imaging with the D1 tracer \[11C\]SCH 23390, and little is known about the role of D1 receptors in vivo and how it relates to clinical phenomena. The aim of the current study is to assess the feasibility and usefulness of imaging of the dopamine D1 receptor and dopamine terminal function in vivo, using PET (positron emission tomography) in patients with PD, with and without dementia, and to assess changes in presynaptic and postsynaptic dopaminergic markers in PD. The long-term goal of the present study is to further our understanding of the role of the dopaminergic system in the pathogenesis of PD and its relationship with cognitive and motor deficits of PD. Knowledge gained from the present study may assist in the development of novel therapeutic targets for PD.