Neuronal injury biomarkers and prognosis in ADNI subjects with normal cognition

• Published in: Acta neuropathologica communications 2014-03, Vol.2 (1), p.26-26, Article 26
• Main Authors: Toledo, Jon B, Weiner, Michael W, Wolk, David A, Da, Xiao, Chen, Kewei, Arnold, Steven E, Jagust, William, Jack, Clifford, Reiman, Eric M, Davatzikos, Christos, Shaw, Leslie M, Trojanowski, John Q
• Format: Article
• Language: English
• Subjects: Advertising executives; Aged; Aged, 80 and over; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Amyloid beta-Peptides - cerebrospinal fluid; Biomarkers - cerebrospinal fluid; Brain - diagnostic imaging; Brain - pathology; Cognition - physiology; Cognitive Dysfunction - diagnosis; Cohort Studies; Communications industry; Cross-Sectional Studies; Databases, Factual - statistics & numerical data; Disease Progression; Female; Fluorodeoxyglucose F18; Humans; Male; Neuropsychological Tests; Peptide Fragments - cerebrospinal fluid; PET imaging; Pharmaceutical industry; Psychiatric Status Rating Scales; Radionuclide Imaging; tau Proteins - cerebrospinal fluid; Telecommunications services industry; Time Factors
• ISSN: 2051-5960; 2051-5960
• DOI: 10.1186/2051-5960-2-26

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. 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. 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.