title: 123I-Iodobenzovesamicol SPECT Imaging of Cholinergic Systems in Dementia with Lewy Bodies.
abstract: Cholinergic alterations in dementia with Lewy bodies (DLB) have been widely documented in postmortem studies, whereas in vivo studies are sparse, particularly at the subcortical level. We used123I-iodobenzovesamicol, a SPECT radiotracer of the vesicular acetylcholine transporter, to evaluate in vivo in DLB the integrity of the 3 main cholinergic pathways-the Ch1 (septohippocampal), the Ch4 (innominatocortical), and the Ch5 (pontothalamic) cholinergic pathways-as well as the striatal cholinergic interneurons. In addition, we assessed the involvement of the cholinergic system in cognitive and neuropsychiatric disorders in DLB patients.
  
  
  METHODS
  Twelve healthy volunteers (median age, 72 y; interquartile range, 6.25 y) and 11 DLB patients (median age, 76 y; interquartile range, 10.50 y) underwent a dynamic123I-iodobenzovesamicol SPECT scan and an MRI scan. MR images were automatically segmented, providing the volumes of several regions of interest, including the striatum and cholinergic terminals in Ch1 (hippocampus), Ch4 (cortical lobes), and Ch5 (thalamus). For each region of interest and each subject, pharmacokinetic modeling allowed calculation of the nondisplaceable binding potential (BPND) values for the binding of123I-iodobenzovesamicol to the vesicular acetylcholine transporter. A neuropsychological evaluation of participants was performed with the Mini-Mental State Examination and the Grober-Buschke, Set, visual discrimination, Benton, and Wechsler tests, and cognitive fluctuations and apathy were also assessed.
  
  
  RESULTS
  Compared with BPNDvalues for healthy subjects, BPNDvalues for DLB patients were significantly lower in the Ch4 terminal regions of the anterior cingulate cortex and the superior and inferior parietal cortices (P = 0.0006, 0.0015, and 0.0023, respectively), in the Ch5 terminal region of the thalamus (P = 0.0003), and in the striatum (P = 0.0042). All of the neuropsychological test scores were significantly lower in DLB patients than in healthy subjects. Four DLB patients with apathy and 4 DLB patients without apathy were identified. For the anterior cingulate cortex, compared with BPNDvalues in healthy subjects, BPNDvalues were significantly lower in patients with apathy (P = 0.004) and were unchanged in patients without apathy.
  
  
  CONCLUSIONS
  Our results confirm the existence in DLB of cholinergic alterations, reaching both cortical and subcortical levels, including the Ch5 pathway and the striatum. Alterations in cholinergic transmission in the anterior cingulate cortex could be closely associated with the development of apathy.
authors.affiliation: Université de Bordeaux, INCIA, UMR 5287, Bordeaux, France joachim.mazere@chu-bordeaux.fr.|CNRS, INCIA, UMR 5287, Bordeaux, France.|Service de Médecine Nucléaire, CHU de Bordeaux, Bordeaux, France; and.
authors.forename: Joachim
authors.initials: J
authors.lastname: Mazère
authors.affiliation: Université de Bordeaux, INCIA, UMR 5287, Bordeaux, France.|CNRS, INCIA, UMR 5287, Bordeaux, France.|Service de Médecine Nucléaire, CHU de Bordeaux, Bordeaux, France; and.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lamare
authors.affiliation: Université de Bordeaux, INCIA, UMR 5287, Bordeaux, France.|CNRS, INCIA, UMR 5287, Bordeaux, France.|Service de Médecine Nucléaire, CHU de Bordeaux, Bordeaux, France; and.|EPHE, Paris, France.
authors.forename: Michele
authors.initials: M
authors.lastname: Allard
authors.affiliation: Université de Bordeaux, INCIA, UMR 5287, Bordeaux, France.|CNRS, INCIA, UMR 5287, Bordeaux, France.|Service de Médecine Nucléaire, CHU de Bordeaux, Bordeaux, France; and.
authors.forename: Philippe
authors.initials: P
authors.lastname: Fernandez
authors.affiliation: Université de Bordeaux, INCIA, UMR 5287, Bordeaux, France.|CNRS, INCIA, UMR 5287, Bordeaux, France.
authors.forename: Willy
authors.initials: W
authors.lastname: Mayo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D059329:Cholinergic Neurons / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000378:metabolism; D010880:Piperidines / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013764:Tetrahydronaphthalenes / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism
chemical_list: D010880:Piperidines; D019275:Radiopharmaceuticals; D013764:Tetrahydronaphthalenes; D050494:Vesicular Acetylcholine Transport Proteins; C065043:5-iodobenzovesamicol
keywords: 123I-iodobenzovesamicol; SPECT; apathy; cholinergic pathways; dementia with Lewy Bodies