title: Reduced alpha4beta2*-nicotinic acetylcholine receptor binding and its relationship to mild cognitive and depressive symptoms in Parkinson disease.
abstract: BACKGROUND
  Cognitive or depressive disorders are frequently noted in patients with Parkinson disease (PD) and may be related to altered signaling through alpha4beta2*-nicotinic acetylcholine receptors (alpha4beta2*-nAChRs).
  
  
  OBJECTIVE
  To assess the availability of alpha4beta2*-nAChRs and their relationship to mild cognitive and mild depressive symptoms in vivo in patients with PD.
  
  
  METHODS
  Crossover comparison between patients with PD and healthy volunteers (control group) using the alpha4beta2*-nAChR-specific radioligand 2-[(18)F]fluoro-3-(2[S]-2-azetidinylmethoxy)-pyridine (2-[(18)F]FA-85380) and positron emission tomography.
  
  
  METHODS
  Departments of Neurology and Nuclear Medicine, University of Leipzig, Leipzig, Germany.
  
  
  METHODS
  Twenty-two nonsmoking patients with PD and 9 nonsmoking healthy volunteers.
  
  
  METHODS
  Level of 2-[(18)F]FA-85380 binding potential (2-FA BP), a measure of alpha4beta2*-nAChR availability. The relationship between severity of cognitive symptoms as rated using the Mini-Mental State Examination and DemTect scale and the level of depressive symptoms as indicated using the Beck Depression Inventory, and 2-FA BP were assessed.
  
  
  RESULTS
  In patients with PD compared with healthy volunteers, there was widespread reduced 2-FA BP, especially in the midbrain, pons, anterior cingulate cortex, frontoparietal cortex, and cerebellum. In subgroups of patients with PD with possible depression, reduced 2-FA BP was most pronounced in the cingulate cortex and frontoparieto-occipital cortex, whereas in patients with PD with mild cognitive impairment, 2-FA BP was reduced in the midbrain, pons, and cerebellum. In patients with PD, the strongest associations between depressive symptoms and reduced 2-FA BP were noted in the anterior cingulate cortex, putamen, midbrain, and occipital cortex. In contrast, cognitive symptoms correlated only weakly with reduced 2-FA BP in the thalamus, midbrain, temporal cortex, hippocampus, and cerebellum.
  
  
  CONCLUSIONS
  There is a broad reduction of alpha4beta2*-nAChR availability in patients with PD without clinically manifest dementia or depression compared with healthy volunteers. Reduced alpha4beta2*-nAChR binding in patients with PD within the subcortical and cortical regions is associated with the severity of mild cognitive or depressive symptoms. These results provide novel in vivo evidence for a role of the cholinergic neurotransmission in psychiatric comorbidity of PD.
authors: Department of Nuclear Medicine, University of Leipzig, Liebigstr 18, 04103 Leipzig, Germany. philipp.meyer@medizin.uni-leipzig.de
authors: Philipp M
authors: PM
authors: Meyer
authors: Karl
authors: K
authors: Strecker
authors: Kai
authors: K
authors: Kendziorra
authors: Georg
authors: G
authors: Becker
authors: Swen
authors: S
authors: Hesse
authors: Dominique
authors: D
authors: Woelpl
authors: Anke
authors: A
authors: Hensel
authors: Marianne
authors: M
authors: Patt
authors: Dietlind
authors: D
authors: Sorger
authors: Florian
authors: F
authors: Wegner
authors: Donald
authors: D
authors: Lobsien
authors: Henryk
authors: H
authors: Barthel
authors: Peter
authors: P
authors: Brust
authors: Hermann J
authors: HJ
authors: Gertz
authors: Osama
authors: O
authors: Sabri
authors: Johannes
authors: J
authors: Schwarz
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003072:Cognition Disorders / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D003863:Depression / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism*; D010555:Personality Inventory; D049268:Positron-Emission Tomography; D011869:Radioligand Assay / Q000706:statistics & numerical data; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012720:Severity of Illness Index; D014018:Tissue Distribution
chemical_list: D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2