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

doi:10.1212/WNL.0000000000011214

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 journal › Article › Academic › peer-review

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 language	English
Pages (from-to)	E619-E631
Number of pages	13
Journal	Neurology
Volume	96
Issue number	4
DOIs	https://doi.org/10.1212/WNL.0000000000011214
Publication status	Published - 26 Jan 2021

Keywords

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

Access to Document

10.1212/WNL.0000000000011214

Cite this

Farrell, M. E., Jiang, S., Schultz, A. P., Properzi, M. J., Price, J. C., Becker, J. A., Jacobs, H. I. L., Hanseeuw, B. J., Rentz, D. M., Villemagne, V. L., Papp, K. V., Mormino, E. C., Betensky, R. A., Johnson, K. A., Sperling, R. A., Buckley, R. F., & Alzheimer's Disease Neuroimaging Initiative (2021). Defining the Lowest Threshold for Amyloid-PET to Predict Future Cognitive Decline and Amyloid Accumulation. Neurology, 96(4), E619-E631. https://doi.org/10.1212/WNL.0000000000011214

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title = "Defining the Lowest Threshold for Amyloid-PET to Predict Future Cognitive Decline and Amyloid Accumulation",

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.",

keywords = "ALZHEIMERS-DISEASE, APOE EPSILON-4, BETA, NEURODEGENERATION, ASSOCIATION, BIOMARKERS, DEPOSITION, PROGRESS, CORE",

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

year = "2021",

month = jan,

day = "26",

doi = "10.1212/WNL.0000000000011214",

language = "English",

volume = "96",

pages = "E619--E631",

journal = "Neurology",

issn = "0028-3878",

publisher = "LIPPINCOTT WILLIAMS & WILKINS",

number = "4",

}

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 2021, 'Defining the Lowest Threshold for Amyloid-PET to Predict Future Cognitive Decline and Amyloid Accumulation', Neurology, vol. 96, no. 4, pp. E619-E631. https://doi.org/10.1212/WNL.0000000000011214

TY - JOUR

T1 - Defining the Lowest Threshold for Amyloid-PET to Predict Future Cognitive Decline and Amyloid Accumulation

AU - Farrell, M.E.

AU - Jiang, S.

AU - Schultz, A.P.

AU - Properzi, M.J.

AU - Price, J.C.

AU - Becker, J.A.

AU - Jacobs, H.I.L.

AU - Hanseeuw, B.J.

AU - Rentz, D.M.

AU - Villemagne, V.L.

AU - Papp, K.V.

AU - Mormino, E.C.

AU - Betensky, R.A.

AU - Johnson, K.A.

AU - Sperling, R.A.

AU - Buckley, R.F.

AU - Alzheimer's Disease Neuroimaging Initiative

PY - 2021/1/26

Y1 - 2021/1/26

N2 - 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.

AB - 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.

KW - ALZHEIMERS-DISEASE

KW - APOE EPSILON-4

KW - BETA

KW - NEURODEGENERATION

KW - ASSOCIATION

KW - BIOMARKERS

KW - DEPOSITION

KW - PROGRESS

KW - CORE

U2 - 10.1212/WNL.0000000000011214

DO - 10.1212/WNL.0000000000011214

M3 - Article

C2 - 33199430

SN - 0028-3878

VL - 96

SP - E619-E631

JO - Neurology

JF - Neurology

IS - 4

ER -