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

被引：77

作者：

Farrell, Michelle E. ^{[1
]}

Jiang, Shu ^{[1
,3
,4
]}

Schultz, Aaron P. ^{[1
]}

Properzi, Michael J. ^{[1
]}

Price, Julie C. ^{[2
]}

Becker, J. Alex ^{[2
]}

Jacobs, Heidi I. L. ^{[2
,5
]}

Hanseeuw, Bernard J. ^{[2
,6
]}

Rentz, Dorene M. ^{[1
,7
]}

Villemagne, Victor L. ^{[8
]}

Papp, Kathryn, V ^{[1
,7
]}

Mormino, Elizabeth C. ^{[9
]}

Betensky, Rebecca A. ^{[1
,3
,10
]}

Johnson, Keith A. ^{[1
,2
]}

Sperling, Reisa A. ^{[1
,7
]}

Buckley, Rachel F. ^{[1
,7
,11
]}

机构：

[1] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA

[2] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA

[3] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA

[4] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA

[5] Maastricht Univ, Alzheimer Ctr Limburg, Sch Mental Hlth & Neurosci, Med & Life Sci,Fac Hlth, Maastricht, Netherlands

[6] Catholic Univ Louvain, Clin Univ St Luc, Brussels, Belgium

[7] Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, 75 Francis St, Boston, MA 02115 USA

[8] Austin Hlth, Dept Mol Imaging & Therapy, Melbourne, Vic, Australia

[9] Stanford Univ, Dept Neurosci, Palo Alto, CA 94304 USA

[10] NYU, Sch Global Publ Hlth, Dept Biostat, New York, NY 10003 USA

[11] Univ Melbourne, Melbourne Sch Psychol Sci, Melbourne, Vic, Australia

来源：

NEUROLOGY | 2021年 / 96卷 / 04期

基金：

加拿大健康研究院;

关键词：

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

D O I：

10.1212/WNL.0000000000011214

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Introduction As 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. Methods Sequential 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). Results Within 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). Discussion These 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.

引用

页码：E619 / E631

页数：13

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