Neuronal injury biomarkers and prognosis in ADNI subjects with normal cognition

Alzheimer’s Disease Neuroimaging Initiative

Research output: Contribution to journalArticle

56 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)26
Number of pages1
JournalActa neuropathologica communications
Volume2
DOIs
StatePublished - 2014

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Neuroimaging
Cognition
Dementia
Biomarkers
Alzheimer Disease
Wounds and Injuries
Cerebrospinal Fluid
Magnetic Resonance Imaging
Cognitive Dysfunction
Positron-Emission Tomography

ASJC Scopus subject areas

  • Medicine(all)

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Neuronal injury biomarkers and prognosis in ADNI subjects with normal cognition. / Alzheimer’s Disease Neuroimaging Initiative.

In: Acta neuropathologica communications, Vol. 2, 2014, p. 26.

Research output: Contribution to journalArticle

Alzheimer’s Disease Neuroimaging Initiative. / Neuronal injury biomarkers and prognosis in ADNI subjects with normal cognition. In: Acta neuropathologica communications. 2014 ; Vol. 2. pp. 26.
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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.",
author = "{Alzheimer’s Disease Neuroimaging Initiative} and Toledo, {Jon B.} and Weiner, {Michael W.} and Wolk, {David A.} and Xiao Da and Kewei Chen and Arnold, {Steven E.} and William Jagust and Jack, {Clifford R Jr.} and Reiman, {Eric M.} and Christos Davatzikos and Shaw, {Leslie M.}",
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AU - Alzheimer’s Disease Neuroimaging Initiative

AU - Toledo, Jon B.

AU - Weiner, Michael W.

AU - Wolk, David A.

AU - Da, Xiao

AU - Chen, Kewei

AU - Arnold, Steven E.

AU - Jagust, William

AU - Jack, Clifford R Jr.

AU - Reiman, Eric M.

AU - Davatzikos, Christos

AU - Shaw, Leslie M.

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N2 - 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.

AB - 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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