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Cited by 167Dementia and Cognitive Impairment ResearchParkinson's Disease Mechanisms and TreatmentsMedical Imaging Techniques and Applications

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Autopsy validation of 123 I-FP-CIT dopaminergic neuroimaging for the diagnosis of DLB

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Thomas, Alan J., Attems, Johannes, Colloby, Sean J., O'Brien, John T., McKeith, Ian, Walker, Rodney, Lee, Lean, Burn, David, Lett, Debra J., Walker, Zuzana·2017·Neurology
DOI 10.1212/wnl.0000000000003512PMC PMC5272795
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Abstract

Objective: To conduct a validation study of 123I-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 undergone 123I-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 underwent 123I-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 normal 123I-FP-CIT imaging. Conclusions: This large autopsy analysis of 123I-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 abnormal 123I-FP-CIT scan strongly supports Lewy body disease, a normal scan does not exclude DLB with minimal brainstem involvement. Classification of evidence: This study provides Class I evidence that 123I-FP-CIT dopaminergic neuroimaging accurately identifies patients with DLB.

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Figure 1 Flowchart showing relationship of clinical diagnosis to autopsy and 123I-FP-CIT imaging findings 123I-FP-CIT = 123I-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane.
Figure 1 Flowchart showing relationship of clinical diagnosis to autopsy and 123I-FP-CIT imaging findings 123I-FP-CIT = 123I-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane.CC BY-NC-ND · PubMed Central
Figure 2 Photomicrographs of typical 123I-FP-CIT–positive, false-negative, and false-positive cases Photomicrographs illustrating a case with clinical dementia with Lewy bodies (DLB) and abnormal (positive) 123I-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane (123I-FP-CIT) scan with marked neuronal dopaminergic cell loss in the substantia nigra (SN) (A) and Lewy bodies in the SN (D) and temporal cortex (G). A false-negative 123I-FP-CIT scan in an individual with clinical and pathologic dementia with Lewy bodies but only mild cell loss (B) and α-synuclein pathology of low severity in the SN (E) and moderate severity in the temporal cortex (H). A false-positive 123I-FP-CIT scan in an individual with clinical and pathologic Alzheimer disease virtually without dopaminergic cell loss in the SN (C) and no α-synuclein pathology in the SN (F) or temporal cortex (I). Scale bar in panel A represents 200 μm and is valid for panels A–F; scale bar in panel G represents 50 μm and is valid for panels G–I. For the dopaminergic neurons, cresyl fast violet was used. For the α-synuclein immunohistochemistry, Novocastra antibody (1:200 dilution) was used with hematoxylin as counterstain.
Figure 2 Photomicrographs of typical 123I-FP-CIT–positive, false-negative, and false-positive cases Photomicrographs illustrating a case with clinical dementia with Lewy bodies (DLB) and abnormal (positive) 123I-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane (123I-FP-CIT) scan with marked neuronal dopaminergic cell loss in the substantia nigra (SN) (A) and Lewy bodies in the SN (D) and temporal cortex (G). A false-negative 123I-FP-CIT scan in an individual with clinical and pathologic dementia with Lewy bodies but only mild cell loss (B) and α-synuclein pathology of low severity in the SN (E) and moderate severity in the temporal cortex (H). A false-positive 123I-FP-CIT scan in an individual with clinical and pathologic Alzheimer disease virtually without dopaminergic cell loss in the SN (C) and no α-synuclein pathology in the SN (F) or temporal cortex (I). Scale bar in panel A represents 200 μm and is valid for panels A–F; scale bar in panel G represents 50 μm and is valid for panels G–I. For the dopaminergic neurons, cresyl fast violet was used. For the α-synuclein immunohistochemistry, Novocastra antibody (1:200 dilution) was used with hematoxylin as counterstain.CC BY-NC-ND · PubMed Central

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  1. Kane J, Barker S, Surendranathan A, et al. Clinical diagnosis of dementia with Lewy bodies in routine secondary care clinical services: results from the DIAMOND-Lewy study. Am J Neurodegenerative Dis 2015;4(suppl 1):178.

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Metadata

Authors
Thomas, A. J., Attems, J., Colloby, S. J., O'Brien, J. T., McKeith, I., Walker, R., Lee, L., Burn, D., Lett, D. J., & Walker, Z.
Affiliations
Barts Health NHS Trust (GB)
Corresponding author
Thomas, Alan J.
ORCID
Venue
Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2017-01-17
Volume
88
Issue
3
Pages
276-283
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
DOI
10.1212/wnl.0000000000003512
PMC
PMC5272795
OpenAlex
W2559951892
Cited by
165
References
33
Citations by year
2026: 6 · 2025: 23 · 2024: 21 · 2023: 15 · 2022: 9 · 2021: 12 · 2020: 22 · 2019: 25 · 2018: 21 · 2017: 11
FWCI
16.88
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Neurology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
  • Apollo
  • Newcastle University ePrints (Newcastle Univesity) (cc-by-nc-nd)
Funders
  • Alzheimer's Society
  • National Institute for Health and Care Research (NF-SI-0611-10048)
  • Newcastle University (G0400074)
  • Cambridge University Hospitals
  • Newcastle upon Tyne Hospitals NHS Foundation Trust
  • Medical Research Council (G0400074)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
Keywords
dementia with Lewy bodies, 123I-FP-CIT, diagnostic accuracy, Lewy body disease, Alzheimer's disease, biomarkers, brainstem involvement
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Autopsy, Female, Humans, Male, Middle Aged, Neurologic Examination, Psychiatric Status Rating Scales, Tropanes, Reproducibility of Results, Tomography, Emission-Computed, Single-Photon, Chi-Square Distribution, Lewy Body Disease

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