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Title: Defining the lowest threshold for amyloid-PET to predict future cognitive decline and amyloid accumulation.
Austin Authors: Farrell, Michelle E;Jiang, Shu;Schultz, Aaron P;Properzi, Michael J;Price, Julie C;Becker, J Alex;Jacobs, Heidi I L;Hanseeuw, Bernard J;Rentz, Dorene M;Villemagne, Victor L ;Papp, Kathryn V;Mormino, Elizabeth C;Betensky, Rebecca A;Johnson, Keith A;Sperling, Reisa A;Buckley, Rachel F
Affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine in St. Louis
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, the Netherlands
Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
Center for Alzheimer Research and Treatment, Brigham and Womens Hospital, Boston, MA, USA
Molecular Imaging and Therapy
Department of Neuroscience, Stanford University, Palo Alto, CA, USA
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
Department of Biostatistics, New York University School of Global Public Health, New York, NY, USA
Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Australia
Issue Date: Jan-2021
Date: 2020-11-16
Publication information: Neurology 2020; 96(4): e619-e631
Abstract: As clinical trials move towards earlier intervention, we sought to redefine the Aβ-PET threshold based on the lowest point in a baseline distribution that robustly predicts future Aβ accumulation and cognitive decline in 3 independent samples of clinically normal individuals. Sequential Aβ cut-offs were tested to identify the lowest cutoff associated with future change in cognition (PACC) and Aβ-PET in clinically-normal participants from the Harvard Aging Brain Study (n = 342), Australian Imaging, Biomarker and Lifestyle study of ageing (n = 157) and Alzheimer's Disease Neuroimaging Initiative (n = 356). Within sample, cutoffs derived from future Aβ-PET accumulation and PACC decline converged on the same inflection point beyond which trajectories diverged from normal. Across samples, optimal cutoffs fell within a short range (Centiloid 15-18.5). These optimized thresholds can help to inform future research and clinical trials targeting early Aβ. Threshold convergence raises the possibility of contemporaneous early changes in Aβ and cognition. This study provides Class II evidence that among clinically normal individuals a specific Aβ-PET threshold is predictive of cognitive decline.
DOI: 10.1212/WNL.0000000000011214
ORCID: 0000-0002-6318-9213
Journal: Neurology
PubMed URL: 33199430
Type: Journal Article
Appears in Collections:Journal articles

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