title: PET Radioligands Reveal the Basis of Dementia in Parkinson's Disease and Dementia with Lewy Bodies.
abstract: BACKGROUND
  Effective therapies for dementia with Lewy bodies (DLB) and Parkinson's disease (PD) dementia will require accurate diagnosis and an understanding of the contribution of distinct molecular pathologies to these diseases. We seek to use imaging biomarkers to improve diagnostic accuracy and to clarify the contribution of molecular species to cognitive impairment in DLB and PD.
  
  
  CONCLUSIONS
  We have performed cross-sectional and prospective cohort studies in subjects with DLB, PD with normal cognition, PD with mild cognitive impairment and PD with dementia, contrasted with Alzheimer's disease (AD) and healthy control subjects (HCS). Subjects underwent formal neurological examination, detailed neuropsychological assessments, MRI and PET scans with the radioligands altropane (a dopamine transporter, DAT) and Pittsburgh compound B (PiB; β-amyloid). Putamen DAT concentrations were similar in DLB and PD and differentiated them from HCS and AD. Decreased caudate DAT concentration related to functional impairment in DLB but not PD. PiB uptake was greatest in DLB. However, cortical PiB retention was common in PD and predicted cognitive decline. PET imaging of tau aggregates holds promise both to clarify the contribution of tau to cognitive decline in these diseases and to differentiate DLB and PD from the parkinsonian tauopathies.
  
  
  CONCLUSIONS
  Together, DAT and amyloid PET imaging discriminate DLB from PD and from other disease groups and identify pathological processes that contribute to their course. Multimodal PET imaging has the potential to increase the diagnostic accuracy of DLB and PD in the clinic, improve cohort uniformity for clinical trials, and serve as biomarkers for targeted molecular therapies.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Gomperts
authors.forename: Marta
authors.initials: M
authors.lastname: Marquie
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Locascio
authors.forename: Stephen
authors.initials: S
authors.lastname: Bayer
authors.forename: Keith A
authors.initials: KA
authors.lastname: Johnson
authors.forename: John H
authors.initials: JH
authors.lastname: Growdon
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D000814:Aniline Compounds; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D002243:Carbolines; D003042:Cocaine / Q000031:analogs & derivatives; D060825:Cognitive Dysfunction / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology; D003430:Cross-Sectional Studies; D003937:Diagnosis, Differential; D020961:Lewy Body Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology; D011446:Prospective Studies; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D016019:Survival Analysis; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D002243:Carbolines; C102282:N-iodoallyl-2-carbomethoxy-3-(4-fluorophenyl)tropane; D019275:Radiopharmaceuticals; D013844:Thiazoles; D003042:Cocaine; C000591008:7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole