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Cited by 117Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsParkinson's Disease Mechanisms and Treatments

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In vivo retention of 18 F-AV-1451 in corticobasal syndrome

Open access
Smith, Ruben, Schöll, Michael, Widner, Håkan, van Westen, Danielle, Svenningsson, Per, Hägerström, Douglas, Ohlsson, Tomas, Jögi, Jonas, Nilsson, Christer, Hansson, Oskar·2017·Neurology
DOI 10.1212/wnl.0000000000004264PMC PMC5580862
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Abstract

Objective: To study the usefulness of 18F-AV-1451 PET in patients with corticobasal syndrome (CBS). Methods: We recruited 8 patients with CBS, 17 controls, 31 patients with Alzheimer disease (AD), and 11 patients with progressive supranuclear palsy (PSP) from the Swedish BioFINDER study. All patients underwent clinical assessment, 18F-AV-1451 PET, MRI, and quantification of β-amyloid pathology. A subset of participants also underwent 18F-FDG-PET. Results: In the 8 patients with CBS, 6 had imaging findings compatible with the corticobasal degeneration pathology and 2 with typical AD pathology. In the 6 patients with CBS without typical AD pathology, there were substantial retentions of 18F-AV-1451 in the motor cortex, corticospinal tract, and basal ganglia contralateral to the most affected body side. These patients could be clearly distinguished from patients with AD dementia or PSP using 18F-AV-1451. However, cortical atrophy was more widespread than the cortical retention of 18F-AV1451 in these CBS cases, and cortical AV-1451 uptake did not correlate with cortical thickness or glucose hypometabolism. These results are in sharp contrast to AD dementia, where 18F-AV-1451 retention was more widespread than cortical atrophy, and correlated well with cortical thickness and hypometabolism. Conclusions: Patients with CBS without typical AD pathology exhibited AV-1451 retention in the motor cortex, corticospinal tract, and basal ganglia contralateral to the affected body side, clearly different from controls and patients with AD dementia or PSP. However, cortical atrophy measured with MRI and decreased 18F-fluorodeoxyglucose uptake were more widespread than 18F-AV-1451 uptake and probably represent earlier, yet less specific, markers of CBS. Classification of evidence: This study provides Class III evidence that 18F-AV-1451 PET distinguishes between CBS and AD or PSP.

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Figure 1 18F-AV-1451 retention in different brain regions Standardized uptake value ratios (SUVRs) in the basal ganglia (A) and the cerebral cortex (B). Results are shown for corticobasal syndrome (CBS), most affected side (CBSA); CBS, less affected side (CBSLA); and controls. (C) SUVRs in the most atrophic cortical region. GP = globus pallidus; n.s = not significant. ap < 0.05, bp < 0.01, cp < 0.001.
Figure 1 18F-AV-1451 retention in different brain regions Standardized uptake value ratios (SUVRs) in the basal ganglia (A) and the cerebral cortex (B). Results are shown for corticobasal syndrome (CBS), most affected side (CBSA); CBS, less affected side (CBSLA); and controls. (C) SUVRs in the most atrophic cortical region. GP = globus pallidus; n.s = not significant. ap < 0.05, bp < 0.01, cp < 0.001.CC BY · PubMed Central
Figure 2 18F-AV-1451 PET, AV-1451 cortical z scores, and MRI cortical atrophy z scores (A–H) Cases 1 to 8, where A–E represent patients with corticobasal syndrome (CBS), F represents the patient with CBS with a progressive nonfluent aphasia phenotype, and G and H represent CBS cases with Alzheimer disease (AD) pathology. (I) Mean z score maps of the AD dementia control group (n = 31). The transversal images shown in the first column are in neurologic orientation, where left in the image corresponds to the patient’s left side. *The most affected side of the brain in each patient. z Scores are presented for values >1.5. SUVR = standardized uptake value ratio; VBM = voxel-based morphometry.
Figure 2 18F-AV-1451 PET, AV-1451 cortical z scores, and MRI cortical atrophy z scores (A–H) Cases 1 to 8, where A–E represent patients with corticobasal syndrome (CBS), F represents the patient with CBS with a progressive nonfluent aphasia phenotype, and G and H represent CBS cases with Alzheimer disease (AD) pathology. (I) Mean z score maps of the AD dementia control group (n = 31). The transversal images shown in the first column are in neurologic orientation, where left in the image corresponds to the patient’s left side. *The most affected side of the brain in each patient. z Scores are presented for values >1.5. SUVR = standardized uptake value ratio; VBM = voxel-based morphometry.CC BY · PubMed Central
Figure 3 AV-1451 retention in the corticospinal tract (A) z Score maps of AV-1451 uptake in coronal slices transecting the brain. Numbers below the images indicate the Unified Parkinson’s Disease Rating Scale (UPDRS) part III (motor) score. *The most affected side of the brain in each patient. z Scores are presented for values 1.5–7. (B) Standardized uptake value ratios (SUVRs) in the corticospinal tract using the JHU white matter tract atlas. (C) SUVRs in the subcortical white matter underlying the precentral gyrus. (D) SUVRs in the posterior limb of the internal capsule, containing the corticospinal tract. (E) Spearman correlation between SUVRs in the internal capsule and the UPDRS part III. CBSA = corticobasal syndrome most affected side; CBSLA = corticobasal syndrome less affected side; n.s = not significant. ap < 0.05, bp < 0.01, cp < 0.001, dp < 0.0001.
Figure 3 AV-1451 retention in the corticospinal tract (A) z Score maps of AV-1451 uptake in coronal slices transecting the brain. Numbers below the images indicate the Unified Parkinson’s Disease Rating Scale (UPDRS) part III (motor) score. *The most affected side of the brain in each patient. z Scores are presented for values 1.5–7. (B) Standardized uptake value ratios (SUVRs) in the corticospinal tract using the JHU white matter tract atlas. (C) SUVRs in the subcortical white matter underlying the precentral gyrus. (D) SUVRs in the posterior limb of the internal capsule, containing the corticospinal tract. (E) Spearman correlation between SUVRs in the internal capsule and the UPDRS part III. CBSA = corticobasal syndrome most affected side; CBSLA = corticobasal syndrome less affected side; n.s = not significant. ap < 0.05, bp < 0.01, cp < 0.001, dp < 0.0001.CC BY · PubMed Central
Figure 4 Voxel-based analysis of 18F-AV-1451 retention (A–C) Coronal, sagittal, and transversal sections show where the uptake is higher in corticobasal syndrome (CBS) compared to (A) controls, (B) patients with progressive supranuclear palsy (PSP), and (C) patients with Alzheimer disease (AD) (p < 0.001, uncorrected for multiple comparisons). (D) Lateral and inferior views of areas where the signal is higher in AD than in CBS (p < 0.05, corrected for family-wise error). Scales indicate t scores.
Figure 4 Voxel-based analysis of 18F-AV-1451 retention (A–C) Coronal, sagittal, and transversal sections show where the uptake is higher in corticobasal syndrome (CBS) compared to (A) controls, (B) patients with progressive supranuclear palsy (PSP), and (C) patients with Alzheimer disease (AD) (p < 0.001, uncorrected for multiple comparisons). (D) Lateral and inferior views of areas where the signal is higher in AD than in CBS (p < 0.05, corrected for family-wise error). Scales indicate t scores.CC BY · PubMed Central

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Metadata

Authors
Smith, R., Schöll, M., Widner, H., van Westen, D., Svenningsson, P., Hägerström, D., Ohlsson, T., Jögi, J., Nilsson, C., & Hansson, O.
Affiliations
Lund University (SE)
Corresponding author
  • Smith, Ruben
  • Hansson, Oskar
ORCID
Venue
Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2017-08-22
Volume
89
Issue
8
Pages
845-853
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
DOI
10.1212/wnl.0000000000004264
PMC
PMC5580862
OpenAlex
W2739600095
Cited by
117
References
34
Citations by year
2026: 3 · 2025: 8 · 2024: 4 · 2023: 6 · 2022: 17 · 2021: 21 · 2020: 16 · 2019: 18 · 2018: 19 · 2017: 4
FWCI
12.81
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Neurology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • Australian Government
  • Vetenskapsrådet
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords
corticobasal syndrome, 18F-AV-1451, corticobasal degeneration, amyloid PET, Alzheimer's disease, progressive supranuclear palsy, differential diagnosis, cortical atrophy, corticospinal tract, basal ganglia, motor cortex, cortical thickness
MeSH terms
Aged, Alzheimer Disease, Basal Ganglia Diseases, Brain, Brain Mapping, Carbolines, Diagnosis, Differential, Humans, Magnetic Resonance Imaging, Middle Aged, Pyramidal Tracts, Supranuclear Palsy, Progressive, Sweden, Radiopharmaceuticals, Positron-Emission Tomography

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