Correlations between FDG PET glucose uptake-MRI gray matter volume scores and apolipoprotein E Im4 gene dose in cognitively normal adults: A cross-validation study using voxel-based multi-modal partial least squares

• Published in: NeuroImage (Orlando, Fla.) Vol. 60; no. 4; pp. 2316 - 2322
• Main Authors: Chen, Kewei, Ayutyanont, Napatkamon, Langbaum, Jessica BS, Fleisher, Adam S, Reschke, Cole, Lee, Wendy, Liu, Xiaofen, Alexander, Gene E, Bandy, Dan, Caselli, Richard J, Reiman, Eric M
• Format: Journal Article
• Language: English
• Published: 01.05.2012
• Subjects: Algorithms
• ISSN: 1053-8119
• DOI: 10.1016/j.neuroimage.2012.02.005

We previously introduced a voxel-based, multi-modal application of the partial least square algorithm (MMPLS) to characterize the linkage between patterns in a person's complementary complex datasets without the need to correct for multiple regional comparisons. Here we used it to demonstrate a strong correlation between MMPLS scores to characterize the linkage between the covarying patterns of fluorodeoxyglucose positron emission tomography (FDG PET) measurements of regional glucose metabolism and magnetic resonance imaging (MRI) measurements of regional gray matter associated with apolipoprotein E (APOE) Im4 gene dose (i.e., three levels of genetic risk for late-onset Alzheimer's disease (AD)) in cognitively normal, late-middle-aged persons. Coregistered and spatially normalized FDG PET and MRI images from 70% of the subjects (27 Im4 homozygotes, 36 Im4 heterozygotes and 67 Im4 non-carriers) were used in a hypothesis-generating MMPLS analysis to characterize the covarying pattern of regional gray matter volume and cerebral glucose metabolism most strongly correlated with APOE-Im4 gene dose. Coregistered and spatially normalized FDG PET and MRI images from the remaining 30% of the subjects were used in a hypothesis-testing MMPLS analysis to generate FDG PET-MRI gray matter MMPLS scores blind to their APOE genotype and characterize their relationship to APOE-Im4 gene dose. The hypothesis-generating analysis revealed covarying regional gray matter volume and cerebral glucose metabolism patterns that resembled those in traditional univariate analyses of AD and APOE-Im4 gene dose and PET-MRI scores that were strongly correlated with APOE-Im4 gene dose (p < 1 A 10a 16). The hypothesis-testing analysis results showed strong correlations between FDG PET-MRI gray matter scores and APOE-Im4 gene dose (p = 8.7 A 10a 4). Our findings support the possibility of using the MMPLS to analyze complementary datasets from the same person in the presymptomatic detection and tracking of AD.