Unique regional patterns of amyloid burden predict progression to prodromal and clinical stages of Alzheimer's disease

doi:10.1016/j.neurobiolaging.2021.06.014

Published October 1, 2021 | Version v1

Journal article Open

Unique regional patterns of amyloid burden predict progression to prodromal and clinical stages of Alzheimer's disease

1. Department of Nuclear Medicine, Multimodal Neuroimaging Group, University of Cologne, University Hospital of Cologne, Cologne, Germany
2. Department of Nuclear Medicine, Multimodal Neuroimaging Group, University of Cologne, University Hospital of Cologne, Cologne, Germany & Research Center Juelich, Institute for Neuroscience and Medicine II, Molecular Organization of the Brain, Juelich, Germany
3. Department of Nuclear Medicine, Multimodal Neuroimaging Group, University of Cologne, University Hospital of Cologne, Cologne, Germany & German Center for Neurodegenerative Diseases, Bonn/Cologne, Germany
4. Department of Nuclear Medicine, Multimodal Neuroimaging Group, University of Cologne, University Hospital of Cologne, Cologne, Germany & German Center for Neurodegenerative Diseases, Bonn/Cologne, Germany & University of Cologne, University Hospital of Cologne, Department of Neurology, Cologne, Germany
5. Department of Nuclear Medicine, Multimodal Neuroimaging Group, University of Cologne, University Hospital of Cologne, Cologne, Germany & Research Center Juelich, Institute for Neuroscience and Medicine II, Molecular Organization of the Brain, Juelich, Germany & German Center for Neurodegenerative Diseases, Bonn/Cologne, Germany

Abstract:

Although beta-amyloid (Aβ) positivity has shown to be associated with higher risk of progression to Alzheimer's disease (AD) in mild cognitive impairment (MCI), information on the time to conversion to manifest dementia cannot be readily deduced from this binary classification. Here, we assessed if regional patterns of Aβ deposition measured with 18F-florbetapir may serve as biomarker for progression risk in Aβ-positive cognitively normal (CN) and MCI patients, including clinical follow-up data and cerebrospinal fluid (CSF) biomarkers. Voxel-wise group comparisons between age and sex-matched Aβ-positive groups (i.e., CN-stables [n = 38] vs. CN-to-MCI/AD progressors [n = 38], MCI-stables [n = 104] versus MCI-to-AD progressors [n = 104]) revealed higher Aβ burden in precuneus, subcortical, and parietal regions in CN-to-MCI/AD progressors and cingulate, temporal, and frontal regions in MCI-to-AD progressors. Importantly, these regional patterns predicted progression to advanced stages on the AD spectrum in the short and the long-term beyond global Aβ burden and CSF biomarkers. These results suggest that distinct regional patterns of Aβ burden are a valuable biomarker for risk of disease progression in CN and MCI.

Notes

This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 115952. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and EFPIA. This communication reflects the views of the authors and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein.

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