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Applicability of in vivo staging of regional amyloid burden in a cognitively normal cohort with subjective memory complaints: the INSIGHT-preAD study

2019; BioMed Central; Volume: 11; Issue: 1 Linguagem: Inglês

10.1186/s13195-019-0466-3

1758-9193

Fatemah A. Sakr, Michel J. Grothe, Enrica Cavedo, Irina Jelistratova, Marie‐Odile Habert, Martin Dyrba, Gabriel González‐Escamilla, Hugo Bertin, Maxime Locatelli, Stéphane Lehéricy, Stefan Teipel, Bruno Dubois, Harald Hampel, Hovagim Bakardjian, Habib Benali, Hugo Bertin, Joel Bonheur, Laurie Boukadida, Nadia Boukerrou, Enrica Cavedo, Patrizia Chiesa, Olivier Colliot, Bruno Dubois, Marion Dubois, Stéphane Epelbaum, Geoffroy Gagliardi, Remy Genthon, Marie-Odile Habert, Harald Hampel, Marion Houot, Aurélie Kas, Foudil Lamari, M J Levy, Simone Lista, Christiane Metzinger, Fanny Mochel, Francis Nyasse, Catherine Poisson, Marie‐Claude Potier, Marie Revillon, Antonio Santos, Katia Santos Andrade, Marine Sole, Mohmed Surtee, Michel Thiebaud de Schotten, Andrea Vergallo, Nadjia Younsi, Lisi Flores Aguilar, Claudio Babiloni, Filippo Baldacci, Norbert Benda, Keith L. Black, Arun L.W. Bokde, Ubaldo Bonuccelli, Karl Broich, René Sosata Bun, Francesco Cacciola, Juan Carlos Martínez‐Castrillo, Enrica Cavedo, Roberto Ceravolo, Patrizia A. Chiesa, Olivier Colliot, Cristina-Maria Coman, Jean‐Christophe Corvol, A. Claudio Cuello, Jeffrey L. Cummings, Herman Depypere, Bruno Dubois, Andrea Duggento, Stanley Durrleman, Valentina Escott-Price, Howard Federoff, Maria Teresa Ferretti, Massimo S. Fiandaca, Richard A. Frank, Francesco Garaci, Remy Genthon, Nathalie George, Filippo Sean Giorgi, Manuela Graziani, Marion Haberkamp, Marie-Odile Habert, Harald Hampel, Karl Herholz, Eric Karran, Seung Hyun Kim, Yosef Koronyo, Maya Koronyo‐Hamaoui, Foudil Lamari, Todd Langevin, Stéphane Lehéricy, Simone Lista, Jean Lorenceau, Mark Mapstone, Christian Néri, Robert Nisticò, Francis Nyasse-Messene, Sid E. O’bryant, George Perry, Craig Ritchie, Katrine Rojkova, Símone Rossi, Amira Saidi, Emiliano Santarnecchi, Lon S. Schneider, Olaf Sporns, Nicola Toschi, Steven R. Verdooner, Andrea Vergallo, Nicolas Villain, Lindsay A Welikovitch, Janet Woodcock, Erfan Younesi,

Functional Brain Connectivity Studies

Abstract Background Current methods of amyloid PET interpretation based on the binary classification of global amyloid signal fail to identify early phases of amyloid deposition. A recent analysis of 18F-florbetapir PET data from the Alzheimer’s disease Neuroimaging Initiative cohort suggested a hierarchical four-stage model of regional amyloid deposition that resembles neuropathologic estimates and can be used to stage an individual’s amyloid burden in vivo. Here, we evaluated the validity of this in vivo amyloid staging model in an independent cohort of older people with subjective memory complaints (SMC). We further examined its potential association with subtle cognitive impairments in this population at elevated risk for Alzheimer’s disease (AD). Methods The monocentric INSIGHT-preAD cohort includes 318 cognitively intact older individuals with SMC. All individuals underwent 18F-florbetapir PET scanning and extensive neuropsychological testing. We projected the regional amyloid uptake signal into the previously proposed hierarchical staging model of in vivo amyloid progression. We determined the adherence to this model across all cases and tested the association between increasing in vivo amyloid stage and cognitive performance using ANCOVA models. Results In total, 156 participants (49%) showed evidence of regional amyloid deposition, and all but 2 of these (99%) adhered to the hierarchical regional pattern implied by the in vivo amyloid progression model. According to a conventional binary classification based on global signal (SUVR Cereb = 1.10), individuals in stages III and IV were classified as amyloid-positive (except one in stage III), but 99% of individuals in stage I and even 28% of individuals in stage II were classified as amyloid-negative. Neither in vivo amyloid stage nor conventional binary amyloid status was significantly associated with cognitive performance in this preclinical cohort. Conclusions The proposed hierarchical staging scheme of PET-evidenced amyloid deposition generalizes well to data from an independent cohort of older people at elevated risk for AD. Future studies will determine the prognostic value of the staging approach for predicting longitudinal cognitive decline in older individuals at increased risk for AD.