title: Mapping of brain acetylcholinesterase alterations in Lewy body disease by PET.
abstract: OBJECTIVE
  To characterize brain cholinergic deficits in Parkinson disease (PD), PD with dementia (PDD), and dementia with Lewy bodies (DLB).
  
  
  METHODS
  Participants included 18 patients with PD, 21 patients with PDD/DLB, and 26 healthy controls. The PD group consisted of nine patients with early PD, each with a disease duration of less than 3 years, five of whom were de novo PD patients, and nine patients with advanced PD, each with a disease duration greater than or equal to 3 years. The PDD/DLB group consisted of 10 patients with PDD and 11 patients with DLB. All subjects underwent PET scans with N-[11C]-methyl-4-piperidyl acetate to measure brain acetylcholinesterase (AChE) activity. Brain AChE activity levels were estimated voxel-by-voxel in a three-compartment analysis using the arterial input function, and compared among our subject groups through both voxel-based analysis using the statistical parametric mapping software SPM5 and volume-of-interest analysis.
  
  
  RESULTS
  Among patients with PD, AChE activity was significantly decreased in the cerebral cortex and especially in the medial occipital cortex (% reduction compared with the normal mean = -12%) (false discovery rate-corrected p value <0.01). Patients with PDD/DLB, however, had even lower AChE activity in the cerebral cortex (% reduction = -27%) (p < 0.01). There was no significant difference between early PD and advanced PD groups or between DLB and PDD groups in the amount by which regional AChE activity in the brain was reduced.
  
  
  CONCLUSIONS
  Brain cholinergic dysfunction occurs in the cerebral cortex, especially in the medial occipital cortex. It begins in early Parkinson disease, and is more widespread and profound in both Parkinson disease with dementia and dementia with Lewy bodies.
authors.affiliation: Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-shi, Chiba 260-8555, Japan. BQV10131@nifty.ne.jp
authors.forename: H
authors.initials: H
authors.lastname: Shimada
authors.forename: S
authors.initials: S
authors.lastname: Hirano
authors.forename: H
authors.initials: H
authors.lastname: Shinotoh
authors.forename: A
authors.initials: A
authors.lastname: Aotsuka
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: N
authors.initials: N
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Ota
authors.forename: M
authors.initials: M
authors.lastname: Asahina
authors.forename: K
authors.initials: K
authors.lastname: Fukushi
authors.forename: S
authors.initials: S
authors.lastname: Kuwabara
authors.forename: T
authors.initials: T
authors.lastname: Hattori
authors.forename: T
authors.initials: T
authors.lastname: Suhara
authors.forename: T
authors.initials: T
authors.lastname: Irie
mesh_terms: D000109:Acetylcholine / Q000172:deficiency*; D000110:Acetylcholinesterase / Q000032:analysis / Q000378:metabolism*; D000368:Aged; D020532:Basal Nucleus of Meynert / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002799:Cholinergic Fibers / Q000201:enzymology* / Q000473:pathology; D015331:Cohort Studies; D003937:Diagnosis, Differential; D018450:Disease Progression; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D020961:Lewy Body Disease / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009778:Occipital Lobe / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology; D011877:Radionuclide Imaging
chemical_list: D015415:Biomarkers; D000110:Acetylcholinesterase; D000109:Acetylcholine