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Open Access 01-12-2014 | Research

Neuronal injury biomarkers and prognosis in ADNI subjects with normal cognition

Authors: Jon B Toledo, Michael W Weiner, David A Wolk, Xiao Da, Kewei Chen, Steven E Arnold, William Jagust, Clifford Jack, Eric M Reiman, Christos Davatzikos, Leslie M Shaw, John Q Trojanowski, for the Alzheimer’s Disease Neuroimaging Initiative

Published in: Acta Neuropathologica Communications | Issue 1/2014

Abstract

Introduction

Based on previous studies, a preclinical classification for Alzheimer’s disease (AD) has been proposed. However, 1) specificity of the different neuronal injury (NI) biomarkers has not been studied, 2) subjects with subtle cognitive impairment but normal NI biomarkers (SCINIB) have not been included in the analyses and 3) progression to mild cognitive impairment (MCI) or dementia of the AD type (DAT), referred to here as MCI/DAT, varies between studies. Therefore, we analyzed data from 486 cognitively normal (CN) and 327 DAT subjects in the AD Neuroimaging Initiative (ADNI)-1/GO/2 cohorts.

Results

In the ADNI-1 cohort (median follow-up of 6 years), 6.3% and 17.0% of the CN subjects developed MCI/DAT after 3 and 5 years follow-up, respectively. NI biomarker cutoffs [structural magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET) and cerebrospinal fluid (CSF) tau] were established in DAT patients and memory composite scores were calculated in CN subjects in a cross-sectional sample (n = 160). In the complete longitudinally followed CN ADNI cohort (n = 326, median follow-up of 2 years), CSF and MRI values predicted an increased conversion to MCI/DAT. Different NI biomarkers showed important disagreements for classifying subjects as abnormal NI [kappa = (−0.05)-(0.33)] and into AD preclinical groups. SCINIB subjects (5.0%) were more prevalent than AD preclinical stage 3 subjects (3.4%) and showed a trend for increased progression to MCI/DAT.

Conclusions

Different NI biomarkers lead to different classifications of ADNI subjects, while structural MRI and CSF tau measures showed the strongest predictive value for progression to MCI/DAT. The newly defined SCINIB category of ADNI subjects is more prevalent than AD preclinical stage individuals.

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Title: Neuronal injury biomarkers and prognosis in ADNI subjects with normal cognition
Authors: Jon B Toledo
Michael W Weiner
David A Wolk
Xiao Da
Kewei Chen
Steven E Arnold
William Jagust
Clifford Jack
Eric M Reiman
Christos Davatzikos
Leslie M Shaw
John Q Trojanowski
for the Alzheimer’s Disease Neuroimaging Initiative
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Acta Neuropathologica Communications / Issue 1/2014
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/2051-5960-2-26

At a glance: The STEP trials

Springer Medicine

Neuronal injury biomarkers and prognosis in ADNI subjects with normal cognition

Abstract

Introduction

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Introduction

Results

Conclusions

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