期刊
NEUROIMAGE-CLINICAL
卷 4, 期 -, 页码 164-173出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.nicl.2013.11.010
关键词
Early Alzheimer's disease; Biomarkers of AD; Magnetic resonance imaging; Dementia; Mild cognitive impairment; Cerebrospinal fluid; Amyloid
类别
资金
- NIH [R01-AG-14971, AG10124, AG24904, AG028018, AG040271, NIMH T32MH065218, P30 AG010129, K01 AG030514]
- Alfonso Martin Escudero Foundation
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant) [U01 AG024904]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Canadian Institutes of Health Research
- Northern California Institute for Research and Education
This study evaluates the individual, as well as relative and joint value of indices obtained from magnetic resonance imaging (MRI) patterns of brain atrophy (quantified by the SPARE-AD index), cerebrospinal fluid (CSF) biomarkers, APOE genotype, and cognitive performance (ADAS-Cog) in progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) within a variable follow-up period up to 6 years, using data from the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1). SPARE-AD was first established as a highly sensitive and specific MRI-marker of AD vs. cognitively normal (CN) subjects (AUC = 0.98). Baseline predictive values of all aforementioned indices were then compared using survival analysis on 381 MCI subjects. SPARE-AD and ADAS-Cog were found to have similar predictive value, and their combination was significantly better than their individual performance. APOE genotype did not significantly improve prediction, although the combination of SPARE-AD, ADAS-Cog and APOE epsilon 4 provided the highest hazard ratio estimates of 17.8 (last vs. first quartile). In a subset of 192 MCI patients who also had CSF biomarkers, the addition of A beta(1-42), t-tau, and p-tau(181p) to the previous model did not improve predictive value significantly over SPARE-AD and ADAS-Cog combined. Importantly, in amyloid-negative patients with MCI, SPARE-AD had high predictive power of clinical progression. Our findings suggest that SPARE-AD and ADAS-Cog in combination offer the highest predictive power of conversion from MCI to AD, which is improved, albeit not significantly, by APOE genotype. The finding that SPARE-AD in amyloid-negative MCI patients was predictive of clinical progression is not expected under the amyloid hypothesis and merits further investigation. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.
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