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Neuronal injury biomarkers and prognosis in ADNI subjects with normal cognition.
Acta Neuropathol Commun. 2014 Mar 06; 2:26.AN

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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Authors+Show Affiliations

Toledo JB
No affiliation info available
Weiner MW
No affiliation info available
Wolk DA
No affiliation info available
Da X
No affiliation info available
Chen K
No affiliation info available
Arnold SE
No affiliation info available
Jagust W
No affiliation info available
Jack C
No affiliation info available
Reiman EM
No affiliation info available
Davatzikos C
No affiliation info available
Shaw LM
No affiliation info available
Trojanowski JQ
Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. trojanow@mail.med.upenn.edu.
Alzheimer’s Disease Neuroimaging Initiative
No affiliation info available

MeSH

AgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesBiomarkersBrainCognitionCognitive DysfunctionCohort StudiesCross-Sectional StudiesDatabases, FactualDisease ProgressionFemaleFluorodeoxyglucose F18HumansMaleNeuropsychological TestsPeptide FragmentsPsychiatric Status Rating ScalesRadionuclide ImagingTime Factorstau Proteins

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

24602322

Citation

Toledo, Jon B., et al. "Neuronal Injury Biomarkers and Prognosis in ADNI Subjects With Normal Cognition." Acta Neuropathologica Communications, vol. 2, 2014, p. 26.
Toledo JB, Weiner MW, Wolk DA, et al. Neuronal injury biomarkers and prognosis in ADNI subjects with normal cognition. Acta Neuropathol Commun. 2014;2:26.
Toledo, J. B., Weiner, M. W., Wolk, D. A., Da, X., Chen, K., Arnold, S. E., Jagust, W., Jack, C., Reiman, E. M., Davatzikos, C., Shaw, L. M., & Trojanowski, J. Q. (2014). Neuronal injury biomarkers and prognosis in ADNI subjects with normal cognition. Acta Neuropathologica Communications, 2, 26. https://doi.org/10.1186/2051-5960-2-26
Toledo JB, et al. Neuronal Injury Biomarkers and Prognosis in ADNI Subjects With Normal Cognition. Acta Neuropathol Commun. 2014 Mar 6;2:26. PubMed PMID: 24602322.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuronal injury biomarkers and prognosis in ADNI subjects with normal cognition. 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, AU - Reiman,Eric M, AU - Davatzikos,Christos, AU - Shaw,Leslie M, AU - Trojanowski,John Q, AU - ,, Y1 - 2014/03/06/ PY - 2014/02/24/received PY - 2014/02/26/accepted PY - 2014/3/8/entrez PY - 2014/3/8/pubmed PY - 2014/3/8/medline SP - 26 EP - 26 JF - Acta neuropathologica communications JO - Acta Neuropathol Commun VL - 2 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. SN - 2051-5960 UR - https://www.unboundmedicine.com/medline/citation/24602322/Neuronal_injury_biomarkers_and_prognosis_in_ADNI_subjects_with_normal_cognition_ DB - PRIME DP - Unbound Medicine ER -