title: Autopsy validation of 123I-FP-CIT dopaminergic neuroimaging for the diagnosis of DLB.
abstract: OBJECTIVE
  To conduct a validation study of123I-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane (123I-FP-CIT) SPECT dopaminergic imaging in the clinical diagnosis of dementia with Lewy bodies (DLB) with autopsy as the gold standard.
  
  
  METHODS
  Patients >60 years of age with dementia who had undergone123I-FP-CIT imaging in research studies and who had donated their brain tissue to the Newcastle Brain Tissue Resource were included. All had structured clinical research assessments, and clinical diagnoses were applied by consensus panels using international diagnostic criteria. All underwent123I-FP-CIT imaging at baseline, and scans were rated as normal or abnormal by blinded raters. Patients were reviewed in prospective studies and after death underwent detailed autopsy assessment, and neuropathologic diagnoses were applied with the use of standard international criteria.
  
  
  RESULTS
  Fifty-five patients (33 with DLB and 22 with Alzheimer disease) were included. Against autopsy diagnosis,123I-FP-CIT had a balanced diagnostic accuracy of 86% (sensitivity 80%, specificity 92%) compared with clinical diagnosis, which had an accuracy of 79% (sensitivity 87%, specificity 72%). Among patients with DLB, 10% (3 patients) met pathologic criteria for Lewy body disease but had normal123I-FP-CIT imaging.
  
  
  CONCLUSIONS
  This large autopsy analysis of123I-FP-CIT imaging in dementia demonstrates that it is a valid and accurate biomarker for DLB, and the high specificity compared with clinical diagnosis (20% higher) is clinically important. The results need to be replicated with patients recruited from a wider range of settings, including movement disorder clinics and general practice. While an abnormal123I-FP-CIT scan strongly supports Lewy body disease, a normal scan does not exclude DLB with minimal brainstem involvement.
  
  
  METHODS
  This study provides Class I evidence that123I-FP-CIT dopaminergic neuroimaging accurately identifies patients with DLB.
authors.affiliation: From the Institute of Neuroscience (A.J.T., J.A., S.J.C., I.M., D.B., D.J.L.), Newcastle University, Campus for Ageing and Vitality, Newcastle Upon Tyne; Department of Psychiatry (J.T.O.), University of Cambridge School of Clinical Medicine; Department of Neurology (R.W.), Barts Health NHS Trust, Royal London Hospital; North Essex Partnership University NHS Foundation Trust (L.L., Z.W.), Epping; and Division of Psychiatry (Z.W.), University College London, UK. alan.thomas@ncl.ac.uk.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Thomas
authors.affiliation: From the Institute of Neuroscience (A.J.T., J.A., S.J.C., I.M., D.B., D.J.L.), Newcastle University, Campus for Ageing and Vitality, Newcastle Upon Tyne; Department of Psychiatry (J.T.O.), University of Cambridge School of Clinical Medicine; Department of Neurology (R.W.), Barts Health NHS Trust, Royal London Hospital; North Essex Partnership University NHS Foundation Trust (L.L., Z.W.), Epping; and Division of Psychiatry (Z.W.), University College London, UK.
authors.forename: Johannes
authors.initials: J
authors.lastname: Attems
authors.affiliation: From the Institute of Neuroscience (A.J.T., J.A., S.J.C., I.M., D.B., D.J.L.), Newcastle University, Campus for Ageing and Vitality, Newcastle Upon Tyne; Department of Psychiatry (J.T.O.), University of Cambridge School of Clinical Medicine; Department of Neurology (R.W.), Barts Health NHS Trust, Royal London Hospital; North Essex Partnership University NHS Foundation Trust (L.L., Z.W.), Epping; and Division of Psychiatry (Z.W.), University College London, UK.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Colloby
authors.affiliation: From the Institute of Neuroscience (A.J.T., J.A., S.J.C., I.M., D.B., D.J.L.), Newcastle University, Campus for Ageing and Vitality, Newcastle Upon Tyne; Department of Psychiatry (J.T.O.), University of Cambridge School of Clinical Medicine; Department of Neurology (R.W.), Barts Health NHS Trust, Royal London Hospital; North Essex Partnership University NHS Foundation Trust (L.L., Z.W.), Epping; and Division of Psychiatry (Z.W.), University College London, UK.
authors.forename: John T
authors.initials: JT
authors.lastname: O'Brien
authors.affiliation: From the Institute of Neuroscience (A.J.T., J.A., S.J.C., I.M., D.B., D.J.L.), Newcastle University, Campus for Ageing and Vitality, Newcastle Upon Tyne; Department of Psychiatry (J.T.O.), University of Cambridge School of Clinical Medicine; Department of Neurology (R.W.), Barts Health NHS Trust, Royal London Hospital; North Essex Partnership University NHS Foundation Trust (L.L., Z.W.), Epping; and Division of Psychiatry (Z.W.), University College London, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: McKeith
authors.affiliation: From the Institute of Neuroscience (A.J.T., J.A., S.J.C., I.M., D.B., D.J.L.), Newcastle University, Campus for Ageing and Vitality, Newcastle Upon Tyne; Department of Psychiatry (J.T.O.), University of Cambridge School of Clinical Medicine; Department of Neurology (R.W.), Barts Health NHS Trust, Royal London Hospital; North Essex Partnership University NHS Foundation Trust (L.L., Z.W.), Epping; and Division of Psychiatry (Z.W.), University College London, UK.
authors.forename: Rodney
authors.initials: R
authors.lastname: Walker
authors.affiliation: From the Institute of Neuroscience (A.J.T., J.A., S.J.C., I.M., D.B., D.J.L.), Newcastle University, Campus for Ageing and Vitality, Newcastle Upon Tyne; Department of Psychiatry (J.T.O.), University of Cambridge School of Clinical Medicine; Department of Neurology (R.W.), Barts Health NHS Trust, Royal London Hospital; North Essex Partnership University NHS Foundation Trust (L.L., Z.W.), Epping; and Division of Psychiatry (Z.W.), University College London, UK.
authors.forename: Lean
authors.initials: L
authors.lastname: Lee
authors.affiliation: From the Institute of Neuroscience (A.J.T., J.A., S.J.C., I.M., D.B., D.J.L.), Newcastle University, Campus for Ageing and Vitality, Newcastle Upon Tyne; Department of Psychiatry (J.T.O.), University of Cambridge School of Clinical Medicine; Department of Neurology (R.W.), Barts Health NHS Trust, Royal London Hospital; North Essex Partnership University NHS Foundation Trust (L.L., Z.W.), Epping; and Division of Psychiatry (Z.W.), University College London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Burn
authors.affiliation: From the Institute of Neuroscience (A.J.T., J.A., S.J.C., I.M., D.B., D.J.L.), Newcastle University, Campus for Ageing and Vitality, Newcastle Upon Tyne; Department of Psychiatry (J.T.O.), University of Cambridge School of Clinical Medicine; Department of Neurology (R.W.), Barts Health NHS Trust, Royal London Hospital; North Essex Partnership University NHS Foundation Trust (L.L., Z.W.), Epping; and Division of Psychiatry (Z.W.), University College London, UK.
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Lett
authors.affiliation: From the Institute of Neuroscience (A.J.T., J.A., S.J.C., I.M., D.B., D.J.L.), Newcastle University, Campus for Ageing and Vitality, Newcastle Upon Tyne; Department of Psychiatry (J.T.O.), University of Cambridge School of Clinical Medicine; Department of Neurology (R.W.), Barts Health NHS Trust, Royal London Hospital; North Essex Partnership University NHS Foundation Trust (L.L., Z.W.), Epping; and Division of Psychiatry (Z.W.), University College London, UK.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Walker
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging; D001344:Autopsy; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D011569:Psychiatric Status Rating Scales; D015203:Reproducibility of Results; D015899:Tomography, Emission-Computed, Single-Photon; D014326:Tropanes / Q000493:pharmacokinetics*
chemical_list: D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane