Using florbetapir positron emission tomography to explore cerebrospinal fluid cut points and gray zones in small sample sizes

Philip S J Weston; Ross W Paterson; Marc Modat; Ninon Burgos; Manuel J Cardoso; Nadia Magdalinou; Manja Lehmann; John C Dickson; Anna Barnes; Jamshed B Bomanji; Irfan Kayani; David M Cash; Sebastien Ourselin; Jamie Toombs; Michael P Lunn; Catherine J Mummery; Jason D Warren; Martin N Rossor; Nick C Fox; Henrik Zetterberg; Jonathan M Schott

doi:10.1016/j.dadm.2015.10.001

Using florbetapir positron emission tomography to explore cerebrospinal fluid cut points and gray zones in small sample sizes

Alzheimers Dement (Amst). 2015 Nov 2;1(4):440-446. doi: 10.1016/j.dadm.2015.10.001. eCollection 2015 Dec.

Authors

Philip S J Weston¹, Ross W Paterson¹, Marc Modat², Ninon Burgos³, Manuel J Cardoso², Nadia Magdalinou⁴, Manja Lehmann¹, John C Dickson⁵, Anna Barnes⁵, Jamshed B Bomanji⁵, Irfan Kayani⁵, David M Cash¹, Sebastien Ourselin³, Jamie Toombs⁶, Michael P Lunn⁶, Catherine J Mummery¹, Jason D Warren¹, Martin N Rossor¹, Nick C Fox¹, Henrik Zetterberg⁷, Jonathan M Schott¹

Affiliations

¹ Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
² Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK; Transitional Imaging Group, Centre for Medical Image Computing, University College London, London, UK.
³ Transitional Imaging Group, Centre for Medical Image Computing, University College London, London, UK.
⁴ Reta Lila Weston Institute of Neurological Studies, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
⁵ Institute of Nuclear Medicine, University College London Hospitals, London, UK.
⁶ MRC Centre for Neuromuscular Disease, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK.
⁷ MRC Centre for Neuromuscular Disease, Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK; Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Abstract

Introduction: We aimed to assess the feasibility of determining Alzheimer's disease cerebrospinal fluid (CSF) cut points in small samples through comparison with amyloid positron emission tomography (PET).

Methods: Twenty-three individuals (19 patients, four controls) had CSF measures of amyloid beta (Aβ)_1-42 and total tau/Aβ_1-42 ratio, and florbetapir PET. We compared CSF measures with visual and quantitative (standardized uptake value ratio [SUVR]) PET measures of amyloid.

Results: Seventeen of 23 were amyloid-positive on visual reads, and 14 of 23 at an SUVR of ≥1.1. There was concordance (positive/negative on both measures) in 20 of 23, of whom 19 of 20 were correctly classified at an Aβ_1-42 of 630 ng/L, and 20 of 20 on tau/Aβ_1-42 ratio (positive ≥0.88; negative ≤0.34). Three discordant cases had Aβ_1-42 levels between 403 and 729 ng/L and tau/Aβ_1-42 ratios of 0.54-0.58.

Discussion: Comparing amyloid PET and CSF biomarkers provides a means of assessing CSF cut points in vivo, and can be applied to small sample sizes. CSF tau/Aβ_1-42 ratio appears robust at predicting amyloid status, although there are gray zones where there remains diagnostic uncertainty.

Keywords: Amyloid PET; Aβ; Cerebrospinal fluid; Cut points; Diagnosis; Phosphorylated tau; Tau.

Abstract

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