Katarzyna Adamczuk1,2, Jolien Schaeverbeke1,2, Natalie Nelissen1,3, Veerle Neyens1,2, Mathieu Vandenbulcke4, Karolien Goffin5, Johan Lilja6,7, Kelly Hilven8, Patrick Dupont1,2, Koen Van Laere2,5, Rik Vandenberghe9,10,11. 1. Laboratory for Cognitive Neurology, KU Leuven, Herestraat 49, 3000, Leuven, Belgium. 2. Alzheimer Research Centre KU Leuven, Leuven Institute of Neuroscience and Disease, Herestraat 49, 3000, Leuven, Belgium. 3. Department of Psychiatry, Oxford University, OX3 7JX, Oxford, UK. 4. Old Age Psychiatry Department, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. 5. Nuclear Medicine and Molecular Imaging Department, KU Leuven and University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. 6. GE Healthcare, Björkgatan 30, 753 23, Uppsala, Sweden. 7. Uppsala University, Department of Surgical Sciences, Radiology, Uppsala University Hospital, 751 85, Uppsala, Sweden. 8. Laboratory for Neuroimmunology, KU Leuven, Herestraat 49, 3000, Leuven, Belgium. 9. Laboratory for Cognitive Neurology, KU Leuven, Herestraat 49, 3000, Leuven, Belgium. rik.vandenberghe@uz.kuleuven.ac.be. 10. Alzheimer Research Centre KU Leuven, Leuven Institute of Neuroscience and Disease, Herestraat 49, 3000, Leuven, Belgium. rik.vandenberghe@uz.kuleuven.ac.be. 11. Neurology Department, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. rik.vandenberghe@uz.kuleuven.ac.be.
Abstract
PURPOSE: Preclinical, or asymptomatic, Alzheimer's disease (AD) refers to the presence of positive AD biomarkers in the absence of cognitive deficits. This research concept is being applied to define target populations for clinical drug development. In a prospective community-recruited cohort of cognitively intact older adults, we compared two amyloid imaging markers within subjects: (18)F-flutemetamol and (11)C-Pittsburgh compound B (PIB). METHODS: In 32 community-recruited cognitively intact older adults aged between 65 and 80 years, we determined the concordance between binary classification based on (18)F-flutemetamol versus (11)C-PIB according to semiquantitative assessment (standardized uptake value ratio in composite cortical volume, SUVRcomp) and, alternatively, according to visual reads. We also determined the correlation between (18)F-flutemetamol and (11)C-PIB SUVR and evaluated how this was affected by the reference region chosen (cerebellar grey matter versus pons) and the use of partial volume correction (PVC) in this population. RESULTS: Binary classification based on semiquantitative assessment was concordant between (18)F-flutemetamol and (11)C-PIB in 94 % of cases. Concordance of blinded binary visual reads between tracers was 84 %. The Spearman correlation between (18)F-flutemetamol and (11)C-PIB SUVRcomp with cerebellar grey matter as reference region was 0.84, with a slope of 0.98. Correlations in neocortical regions were significantly lower with the pons as reference region. PVC improved the correlation in striatum and medial temporal cortex. CONCLUSION: For the definition of preclinical AD based on (18)F-flutemetamol, concordance with (11)C-PIB was highest using semiquantitative assessment with cerebellar grey matter as reference region.
PURPOSE: Preclinical, or asymptomatic, Alzheimer's disease (AD) refers to the presence of positive AD biomarkers in the absence of cognitive deficits. This research concept is being applied to define target populations for clinical drug development. In a prospective community-recruited cohort of cognitively intact older adults, we compared two amyloid imaging markers within subjects: (18)F-flutemetamol and (11)C-Pittsburgh compound B (PIB). METHODS: In 32 community-recruited cognitively intact older adults aged between 65 and 80 years, we determined the concordance between binary classification based on (18)F-flutemetamol versus (11)C-PIB according to semiquantitative assessment (standardized uptake value ratio in composite cortical volume, SUVRcomp) and, alternatively, according to visual reads. We also determined the correlation between (18)F-flutemetamol and (11)C-PIB SUVR and evaluated how this was affected by the reference region chosen (cerebellar grey matter versus pons) and the use of partial volume correction (PVC) in this population. RESULTS: Binary classification based on semiquantitative assessment was concordant between (18)F-flutemetamol and (11)C-PIB in 94 % of cases. Concordance of blinded binary visual reads between tracers was 84 %. The Spearman correlation between (18)F-flutemetamol and (11)C-PIB SUVRcomp with cerebellar grey matter as reference region was 0.84, with a slope of 0.98. Correlations in neocortical regions were significantly lower with the pons as reference region. PVC improved the correlation in striatum and medial temporal cortex. CONCLUSION: For the definition of preclinical AD based on (18)F-flutemetamol, concordance with (11)C-PIB was highest using semiquantitative assessment with cerebellar grey matter as reference region.
Entities:
Keywords:
Alzheimer’s disease; Amyloid PET; Biomarker; Preclinical AD
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