机构：[1]Department of Neurology, XuanWu Hospital of Capital Medical University, Beijing, China,神经科系统神经内科首都医科大学宣武医院[2]Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom,[3]Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing, China,[4]National Clinical Research Center for Geriatric Disorders, Beijing, China
Objective: To define resilience metrics for cognitive decline based on plasma and cerebrospinal fluid (CSF) amyloid-beta (A beta) and examine the demographic, genetic, and neuroimaging factors associated with interindividual differences among metrics of resilience and to demonstrate the ability of such metrics to predict the diagnostic conversion to mild cognitive impairment (MCI). Methods: In this study, cognitively normal (CN) participants with A beta-positive were included from the Sino Longitudinal Study on Cognitive Decline (SILCODE, n = 100) and Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 144). Using a latent variable model of data, metrics of resilience [brain resilience (BR), cognitive resilience (CR), and global resilience (GR)] were defined based on the plasma A beta and CSF A beta. Linear regression analyses were applied to investigate the association between characteristics of individuals (age, sex, educational level, genetic, and neuroimaging factors) and their resilience. The plausibility of these metrics was tested using linear mixed-effects models and Cox regression models in longitudinal analyses. We also compared the effectiveness of these metrics with conventional metrics in predicting the clinical progression. Results: Although individuals in the ADNI cohort were older (74.68 [5.65] vs. 65.38 [4.66], p < 0.001) and had higher educational levels (16.3 [2.6] vs. 12.6 [2.8], p < 0.001) than those in the SILCODE cohort, similar loadings between resilience and its indicators were found within both models. BR and GR were mainly associated with age, women, and brain volume in both cohorts. Prediction models showed that higher CR and GR were related to better cognitive performance, and specifically, all types of resilience to CSF A beta could predict longitudinal cognitive decline. Conclusion: Different phenotypes of resilience depending on cognition and brain volumes were associated with different factors. Such comprehensive resilience provided insight into the mechanisms of susceptibility for Alzheimer's disease (AD) at the individual level, and interindividual differences in resilience had the potential to predict the disease progression in CN people.
基金：
This article was supported by the National Key Research and
Development Program of China (2018YFC1312000) and the
National Natural Science Foundation of China (61633018). Data
collection and sharing for this project was funded by the
Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National
Institutes of Health Grant U01 AG024904) and the DOD ADNI
(Department of Defense award number W81XWH-12-2-0012).
This ADNI was funded by the National Institute on Aging and
theNational Institute of Biomedical Imaging and Bioengineering,
and through generous contributions from the following:
AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery
Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-
Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan
Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F.
Hoffmann-La Roche Ltd. and its affiliated company Genentech,
Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer
Immunotherapy Research & Development, LLC.; Johnson
& Johnson Pharmaceutical Research & Development LLC.;
Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics,
LLC.; NeuroRx Research; Neurotrack Technologies; Novartis
Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging;
Servier; Takeda Pharmaceutical Company; and Transition
Therapeutics. This Canadian Institutes of Health Research was
providing funds to support the ADNI clinical sites in Canada.
Private sector contributions are facilitated by the Foundation
for the National Institutes of Health (www.fnih.org). This
grantee organization was the Northern California Institute for
Research and Education, and this study was coordinated by
the Alzheimer’s Therapeutic Research Institute at the University
of Southern California. The ADNI data are disseminated
by the Laboratory for Neuro Imaging at the University of
Southern California.
第一作者机构：[1]Department of Neurology, XuanWu Hospital of Capital Medical University, Beijing, China,
通讯作者：
推荐引用方式(GB/T 7714)：
Lin Li,Sun Yu,Wang Xiaoqi,et al.Resilience to Plasma and Cerebrospinal Fluid Amyloid-beta in Cognitively Normal Individuals: Findings From Two Cohort Studies[J].FRONTIERS IN AGING NEUROSCIENCE.2021,13:doi:10.3389/fnagi.2021.610755.
APA：
Lin, Li,Sun, Yu,Wang, Xiaoqi,Su, Li,Wang, Xiaoni...&on behalf of the Alzheimer’s Disease Neuroimaging Initiative.(2021).Resilience to Plasma and Cerebrospinal Fluid Amyloid-beta in Cognitively Normal Individuals: Findings From Two Cohort Studies.FRONTIERS IN AGING NEUROSCIENCE,13,
MLA：
Lin, Li,et al."Resilience to Plasma and Cerebrospinal Fluid Amyloid-beta in Cognitively Normal Individuals: Findings From Two Cohort Studies".FRONTIERS IN AGING NEUROSCIENCE 13.(2021)
