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

NeuroImage: Clinical

Jarcy Zee¹  Sharon X. Xie¹  Leslie Shaw²  Jon B. Toledo²  John Q. Trojanowski²  David A. Wolk³  Amanda Shacklett⁴  Xiao Da⁴  Yangming Ou⁴  Paraskevi Parmpi⁴  Christos Davatzikos⁴ 

[1] Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA;Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA;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;

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

DOI  :  10.1016/j.nicl.2013.11.010

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown