Dataset Information

Neuronal injury biomarkers and prognosis in ADNI subjects with normal cognition.

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.

SUBMITTER: Toledo JB

PROVIDER: S-EPMC4008258 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Publications

Neuronal injury biomarkers and prognosis in ADNI subjects with normal cognition.

Toledo Jon B JB Weiner Michael W MW Wolk David A DA Da Xiao X Chen Kewei K Arnold Steven E SE Jagust William W Jack Clifford C Reiman Eric M EM Davatzikos Christos C Shaw Leslie M LM Trojanowski John Q JQ

Acta neuropathologica communications 20140306

<h4>Introduction</h4>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 analyze ...[more]

PMID: 24602322

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Project description:ImportanceThe role of amyloid in the progression of Alzheimer disease (AD) pathophysiology is of central interest to the design of randomized clinical trials. The presence of amyloid has become a prerequisite for enrollment in several secondary prevention trials for AD, yet the precise effect of elevated amyloid levels on subsequent clinical and biomarker events is less certain.ObjectiveTo explore the effect of elevated amyloid levels on subsequent changes in cognition and biomarkers.Design, setting, and participantsA total of 564 cognitively normal individuals (median age, 78 years) from the Mayo Clinic Study of Aging, a population-based longitudinal study in Olmsted County, Minnesota, with serial cognitive data were selected for this study. The data used in this study were collected from January 12, 2006, to January 9, 2014. Individuals included in this study had undergone magnetic resonance imaging, fluorodeoxyglucose positron emission tomography (FDG-PET), and Pittsburgh Compound B (PiB) PET at baseline were not cognitively impaired at baseline and had at least 1 clinical follow-up. A subset of 286 individuals also underwent serial imaging. Elevated amyloid level was defined as a standardized uptake value ratio of greater than 1.5 on PiB PET. Associations with baseline amyloid status and baseline and longitudinal change in clinical and imaging measures were evaluated after adjusting for age and hippocampal volume. APOE4 effects were also evaluated.Main outcomes and measuresCognitive measures of memory, language, attention/executive function, visuospatial skills, PiB levels, hippocampal and ventricular volumes, and FDG-PET measures.ResultsAt baseline, 179 (31.7%) individuals with elevated amyloid levels had poorer cognition in all domains measured, reduced hippocampal volume, and greater FDG-PET hypometabolism. Elevated amyloid levels at baseline were associated with a greater rate of cognitive decline in all domains (0.04 to 0.09 z score units per year) except language and a greater rate of amyloid accumulation (1.6% per year), hippocampal atrophy (30 mm3 per year), and ventricular enlargement (565 mm3 per year). Elevated amyloid levels were also associated with an increased risk of mild cognitive impairment (hazard ratio, 2.9; 95% CI, 1.7-5.0, and hazard ratio, 1.6; 95% CI, 0.9-2.8, for PiB+ APOE4 carriers and PiB+ noncarriers, respectively, compared with PiB- noncarriers). These associations were largely independent of APOE4.Conclusions and relevanceIn persons selected from a population-based study, elevated amyloid levels at baseline were associated with worse cognition and imaging biomarkers at baseline and with greater clinical decline and neurodegeneration. These results have implications for the design of randomized clinical trials for AD.

Dataset Information

Neuronal injury biomarkers and prognosis in ADNI subjects with normal cognition.

Introduction

Results

Conclusions

Publications

Neuronal injury biomarkers and prognosis in ADNI subjects with normal cognition.

Similar Datasets

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