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Neuroimage Clin. 2013 Nov 28;4:164-73. doi: 10.1016/j.nicl.2013.11.010. eCollection 2014.

Integration and relative value of biomarkers for prediction of MCI to AD progression: spatial patterns of brain atrophy, cognitive scores, APOE genotype and CSF biomarkers.

Author information

1
Section of Biomedical Image Analysis, Department of Radiology, and Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA.
2
Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
3
Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
4
Memory Center, University of Pennsylvania, Philadelphia, PA, USA ; Section of Biomedical Image Analysis, Department of Radiology, and Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, USA.

Abstract

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 ε4 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 Aβ1-42, t-tau, and p-tau181p 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.

KEYWORDS:

Amyloid; Biomarkers of AD; Cerebrospinal fluid; Dementia; Early Alzheimer's disease; Magnetic resonance imaging; Mild cognitive impairment

PMID:
24371799
PMCID:
PMC3871290
DOI:
10.1016/j.nicl.2013.11.010
[Indexed for MEDLINE]
Free PMC Article

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