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

Abstract:

INTRODUCTION:As clinical trials move toward earlier intervention, we sought to redefine the β-amyloid (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. METHODS:Sequential Aβ cutoffs were tested to identify the lowest cutoff associated with future change in cognition (Preclinical Alzheimer Cognitive Composite [PACC]) and Aβ-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). RESULTS:Within samples, 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). DISCUSSION: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. CLASSIFICATION OF EVIDENCE:This study provides Class II evidence that among clinically normal individuals a specific Aβ-PET threshold is predictive of cognitive decline.

journal_name

Neurology

journal_title

Neurology

authors

Farrell ME,Jiang S,Schultz AP,Properzi MJ,Price JC,Becker JA,Jacobs HIL,Hanseeuw BJ,Rentz DM,Villemagne VL,Papp KV,Mormino EC,Betensky RA,Johnson KA,Sperling RA,Buckley RF,Alzheimer's Disease Neuroimaging Initiative and t

doi

10.1212/WNL.0000000000011214

subject

Has Abstract

pub_date

2021-01-26 00:00:00

pages

e619-e631

issue

4

eissn

0028-3878

issn

1526-632X

pii

WNL.0000000000011214

journal_volume

96

pub_type

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