Defining the Lowest Threshold for Amyloid-PET to Predict Future Cognitive Decline and Amyloid Accumulation

M.E. Farrell, S. Jiang, A.P. Schultz, M.J. Properzi, J.C. Price, J.A. Becker, H.I.L. Jacobs, B.J. Hanseeuw, D.M. Rentz, V.L. Villemagne, K.V. Papp, E.C. Mormino, R.A. Betensky, K.A. Johnson, R.A. Sperling, R.F. Buckley*, Alzheimer's Disease Neuroimaging Initiative

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Web of Science)

Abstract

IntroductionAs clinical trials move toward earlier intervention, we sought to redefine the beta-amyloid (A beta)-PET threshold based on the lowest point in a baseline distribution that robustly predicts future A beta accumulation and cognitive decline in 3 independent samples of clinically normal individuals.MethodsSequential A beta cutoffs were tested to identify the lowest cutoff associated with future change in cognition (Preclinical Alzheimer Cognitive Composite [PACC]) and A beta-PET in clinically normal participants from the Harvard Aging Brain Study (n = 342), Australian Imaging, Biomarker and Lifestyle study of aging (n = 157), and Alzheimer's Disease Neuroimaging Initiative (n = 356).ResultsWithin samples, cutoffs derived from future A beta-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).DiscussionThese optimized thresholds can help to inform future research and clinical trials targeting early A beta. Threshold convergence raises the possibility of contemporaneous early changes in A beta and cognition.
Original languageEnglish
Pages (from-to)E619-E631
Number of pages13
JournalNeurology
Volume96
Issue number4
DOIs
Publication statusPublished - 26 Jan 2021

Keywords

  • ALZHEIMERS-DISEASE
  • APOE EPSILON-4
  • BETA
  • NEURODEGENERATION
  • ASSOCIATION
  • BIOMARKERS
  • DEPOSITION
  • PROGRESS
  • CORE

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