title: Cognitive executive impairment and dopaminergic deficits in de novo Parkinson's disease.
abstract: Cognitive impairment in Parkinson's disease (PD) is common and does directly impact patients' everyday functioning. However, the underlying mechanisms of early cognitive decline are not known. This study explored the association between striatal dopaminergic deficits and cognitive impairment within a large cohort of early, drug-naïve PD patients and tested the hypothesis that executive dysfunction in PD is associated with striatal dopaminergic depletion. A cross-sectional multicenter cohort of 339 PD patients and 158 healthy controls from the Parkinson's Progression Markers Initiative study was analyzed. Each individual underwent cerebral single-photon emission CT (SPECT) and a standardized neuropsychological assessment with tests of memory as well as visuospatial and executive function. SPECT imaging was performed with [(123) I]FP-CIT, and specific binding ratios in left and right putamen and caudate nucleus were calculated. The association between specific binding ratios, cognitive domain scores, and age was analyzed using Pearson's correlations, partial correlation, and conditional process analysis. A small, but significant, positive association between total striatal dopamine transporter binding and the attention/executive domain was found (r = 0.141; P = 0.009) in PD, but this was not significant after adjusting for age. However, in a moderated mediation model, we found that cognitive executive differences between controls and patients with PD were mediated by an age-moderated striatal dopaminergic deficit. Our findings support the hypothesis that nigrostriatal dopaminergic deficit is associated with executive impairment, but not to memory or visuospatial impairment, in early PD.
authors.affiliation: Center for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Françoise J
authors.initials: FJ
authors.lastname: Siepel
authors.forename: Kolbjørn S
authors.initials: KS
authors.lastname: Brønnick
authors.forename: Jan
authors.initials: J
authors.lastname: Booij
authors.forename: Bernard M
authors.initials: BM
authors.lastname: Ravina
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Lebedev
authors.forename: Joana B
authors.initials: JB
authors.lastname: Pereira
authors.forename: Renate
authors.initials: R
authors.lastname: Grüner
authors.forename: Dag
authors.initials: D
authors.lastname: Aarsland
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003072:Cognition Disorders / Q000175:diagnosis* / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D003430:Cross-Sectional Studies; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis / Q000503:physiopathology*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014326:Tropanes
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; D004298:Dopamine
keywords: Parkinson's disease; SPECT; [123I]FP-CIT; cognitive impairment; dopamine transporter