title: Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study.
abstract: BACKGROUND
  Dementia with Lewy bodies (DLB) needs to be distinguished from other types of dementia because of important differences in patient management and outcome. Current clinically based diagnostic criteria for DLB have limited accuracy. Severe nigrostriatal dopaminergic degeneration occurs in DLB, but not in Alzheimer's disease or most other dementia subtypes, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the sensitivity and specificity, in the ante-mortem differentiation of probable DLB from other causes of dementia, of single photon emission computed tomography (SPECT) brain imaging with the ligand (123)I-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT), which binds to the dopamine transporter (DAT) reuptake site. Diagnostic accuracy, positive and negative predictive values, and inter-reader agreement were the secondary endpoints and a subgroup of possible DLB patients was also included.
  
  
  METHODS
  We did a phase III study in which we used a (123)I-FP-CIT SPECT scan to assess 326 patients with clinical diagnoses of probable (n=94) or possible (n=57) DLB or non-DLB dementia (n=147) established by a consensus panel (in 28 patients no diagnosis could be made). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The study had 90% power to detect the differences between our anticipated sensitivity (0.80) and specificity (0.85) targets and prespecified lower thresholds (sensitivity 0.65, specificity 0.73) using one-sided binomial tests with a significance level of alpha=0.025.
  
  
  RESULTS
  Abnormal scans had a mean sensitivity of 77.7% for detecting clinical probable DLB, with specificity of 90.4% for excluding non-DLB dementia, which was predominantly due to Alzheimer's disease. A mean value of 85.7% was achieved for overall diagnostic accuracy, 82.4% for positive predictive value, and 87.5% for negative predictive value. Inter-reader agreement for rating scans as normal or abnormal was high (Cohen's kappa=0.87). The procedure was well tolerated with few adverse events.
  
  
  CONCLUSIONS
  A revision of the International Consensus Criteria for DLB has recommended that low DAT uptake in the basal ganglia, as shown by SPECT or PET imaging, be a suggestive feature for diagnosis. Our findings confirm the high correlation between abnormal (low binding) DAT activity measured with (123)I-FP-CIT SPECT and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from Alzheimer's disease.
authors.affiliation: Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK. i.g.mckeith@ncl.ac.uk
authors.forename: Ian
authors.initials: I
authors.lastname: McKeith
authors.forename: John
authors.initials: J
authors.lastname: O'Brien
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Walker
authors.forename: Klaus
authors.initials: K
authors.lastname: Tatsch
authors.forename: Jan
authors.initials: J
authors.lastname: Booij
authors.forename: Jacques
authors.initials: J
authors.lastname: Darcourt
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.forename: Raffaele
authors.initials: R
authors.lastname: Giubbini
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Bonuccelli
authors.forename: Duccio
authors.initials: D
authors.lastname: Volterrani
authors.forename: Clive
authors.initials: C
authors.lastname: Holmes
authors.forename: Paul
authors.initials: P
authors.lastname: Kemp
authors.forename: Naji
authors.initials: N
authors.lastname: Tabet
authors.forename: Ines
authors.initials: I
authors.lastname: Meyer
authors.forename: Cornelia
authors.initials: C
authors.lastname: Reininger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D001667:Binding, Competitive / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000502:physiology; D003937:Diagnosis, Differential; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000032:analysis* / Q000378:metabolism; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014326:Tropanes
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; D004298:Dopamine