Abstract

Objectives: The aetiology of the cognitive changes seen in Parkinson’s disease (PD) is multifactorial but it is likely that a significant contribution arises from the disruption of dopaminergic pathways. This study aimed to investigate the contribution of the dopaminergic system to performance on two executive tasks using ¹⁸F-6-fluorodopa positron emission tomography (¹⁸F-dopa PET) in PD subjects with early cognitive changes.

Methods: 16 non-demented, non-depressed PD subjects were evaluated with the Tower of London (TOL) spatial planning task, a verbal working memory task (VWMT) and ¹⁸F-dopa PET, all known to be affected in early PD. Statistical parametric mapping (SPM) localised brain regions in which ¹⁸F-dopa uptake covaried with performance scores. Frontal cortical resting glucose metabolism was assessed with ¹⁸F-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) PET.

Results: SPM localised significant covariation between right caudate ¹⁸F-dopa uptake (Ki) and TOL scores and between left anterior putamen Ki and VWMT performance. No significant covariation was found between task scores and ¹⁸F-dopa Ki values in either limbic or cortical regions. Frontal cortical glucose metabolism was preserved in all cases.

Conclusions: These findings support a causative role of striatal dopaminergic depletion in the early impairment of executive functions seen in PD. They suggest that spatial and verbal executive tasks require integrity of the right and left striatum, respectively, and imply that the pattern of cognitive changes manifest by a patient with PD may reflect differential dopamine loss in the two striatal complexes.