title: Salience network and parahippocampal dopamine dysfunction in memory-impaired Parkinson disease.
abstract: OBJECTIVE
  Patients with Parkinson disease (PD) and mild cognitive impairment (MCI) are vulnerable to dementia and frequently experience memory deficits. This could be the result of dopamine dysfunction in corticostriatal networks (salience, central executive networks, and striatum) and/or the medial temporal lobe. Our aim was to investigate whether dopamine dysfunction in these regions contributes to memory impairment in PD.
  
  
  METHODS
  We used positron emission tomography imaging to compare D2 receptor availability in the cortex and striatal (limbic and associative) dopamine neuron integrity in 4 groups: memory-impaired PD (amnestic MCI; n = 9), PD with nonamnestic MCI (n = 10), PD without MCI (n = 11), and healthy controls (n = 14). Subjects were administered a full neuropsychological test battery for cognitive performance.
  
  
  RESULTS
  Memory-impaired patients demonstrated more significant reductions in D2 receptor binding in the salience network (insular cortex and anterior cingulate cortex [ACC] and the right parahippocampal gyrus [PHG]) compared to healthy controls and patients with no MCI. They also presented reductions in the right insula and right ACC compared to nonamnestic MCI patients. D2 levels were correlated with memory performance in the right PHG and left insula of amnestic patients and with executive performance in the bilateral insula and left ACC of all MCI patients. Associative striatal dopamine denervation was significant in all PD patients.
  
  
  CONCLUSIONS
  Dopaminergic differences in the salience network and the medial temporal lobe contribute to memory impairment in PD. Furthermore, these findings indicate the vulnerability of the salience network in PD and its potential role in memory and executive dysfunction.
authors.affiliation: Morton and Gloria Shulman Movement Disorder Unit and Edmond J. Safra Program in Parkinson Disease, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada; Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada; Division of Brain, Imaging, and Behaviour-Systems Neuroscience, Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Leigh
authors.initials: L
authors.lastname: Christopher
authors.forename: Sarah
authors.initials: S
authors.lastname: Duff-Canning
authors.forename: Yuko
authors.initials: Y
authors.lastname: Koshimori
authors.forename: Barbara
authors.initials: B
authors.lastname: Segura
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boileau
authors.forename: Robert
authors.initials: R
authors.lastname: Chen
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.forename: Pablo
authors.initials: P
authors.lastname: Rusjan
authors.forename: Antonio P
authors.initials: AP
authors.lastname: Strafella
mesh_terms: D000368:Aged; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000000981:diagnostic imaging / Q000378:metabolism*; D008875:Middle Aged; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000378:metabolism*; D020534:Parahippocampal Gyrus / Q000000981:diagnostic imaging / Q000378:metabolism*; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000378:metabolism
chemical_list: D017448:Receptors, Dopamine D2; D004298:Dopamine