title: Prefrontal dopaminergic receptor abnormalities and executive functions in Parkinson's disease.
abstract: The main pattern of cognitive impairments seen in early to moderate stages of Parkinson's disease (PD) includes deficits of executive functions. These nonmotor complications have a significant impact on the quality of life and day-to-day activities of PD patients and are not effectively managed by current therapies, a problem which is almost certainly due to the fact that the disease extends beyond the nigrostriatal system. To investigate the role of extrastriatal dopamine in executive function in PD, PD patients and a control group were studied with positron-emission-tomography using a high-affinity dopamine D2/D3 receptor tracer, [(11) C]FLB-457. All participants were scanned twice while performing an executive task and a control task. Patients were off medication for at least 12 h. The imaging analysis revealed that parkinsonian patients had lower [(11) C]FLB-457 binding than control group independently of task conditions across different brain regions. Cognitive assessment measures were positively correlated with [(11) C]FLB-457 binding in the bilateral dorsolateral prefrontal cortex and anterior cingulate cortex only in control group, but not in PD patients. Within the control group, during the executive task (as compared to control task), there was evidence of reduced [(11) C]FLB-457 binding (indicative of increased dopamine release) in the right orbitofrontal cortex. In contrast, PD patients did not show any reduction in binding during the executive task (as compared with control task). These findings suggest that PD patients present significant abnormalities in extrastriatal dopamine associated with executive processing. These observations provide important insights on the pathophysiology of cognitive dysfunction in PD.
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Ko
authors.forename: Francesca
authors.initials: F
authors.lastname: Antonelli
authors.forename: Oury
authors.initials: O
authors.lastname: Monchi
authors.forename: Nicola
authors.initials: N
authors.lastname: Ray
authors.forename: Pablo
authors.initials: P
authors.lastname: Rusjan
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
authors.forename: Leigh
authors.initials: L
authors.lastname: Christopher
authors.forename: Antonio P
authors.initials: AP
authors.lastname: Strafella
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D003072:Cognition Disorders / Q000209:etiology*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology*; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D011569:Psychiatric Status Rating Scales; D011759:Pyrrolidines / Q000493:pharmacokinetics; D011954:Receptors, Dopamine / Q000378:metabolism*; D012457:Salicylamides / Q000493:pharmacokinetics; D013223:Statistics as Topic; D018709:Statistics, Nonparametric
chemical_list: D002247:Carbon Isotopes; D018492:Dopamine Antagonists; D011759:Pyrrolidines; D011954:Receptors, Dopamine; D012457:Salicylamides; C065065:FLB 457