title: Correlations between FDG PET glucose uptake-MRI gray matter volume scores and apolipoprotein E ε4 gene dose in cognitively normal adults: a cross-validation study using voxel-based multi-modal partial least squares.
abstract: 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) ε4 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 ε4 homozygotes, 36 ε4 heterozygotes and 67 ε4 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-ε4 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-ε4 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-ε4 gene dose and PET-MRI scores that were strongly correlated with APOE-ε4 gene dose (p<1 × 10(-16)). The hypothesis-testing analysis results showed strong correlations between FDG PET-MRI gray matter scores and APOE-ε4 gene dose (p = 8.7 × 10(-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.
authors.affiliation: Banner Alzheimer's Institute and Banner Good Samaritan PET Center, Phoenix, AZ, USA. kewei.chen@asu.edu
authors.forename: Kewei
authors.initials: K
authors.lastname: Chen
authors.forename: Napatkamon
authors.initials: N
authors.lastname: Ayutyanont
authors.forename: Jessica B S
authors.initials: JB
authors.lastname: Langbaum
authors.forename: Adam S
authors.initials: AS
authors.lastname: Fleisher
authors.forename: Cole
authors.initials: C
authors.lastname: Reschke
authors.forename: Wendy
authors.initials: W
authors.lastname: Lee
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Liu
authors.forename: Gene E
authors.initials: GE
authors.lastname: Alexander
authors.forename: Dan
authors.initials: D
authors.lastname: Bandy
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Caselli
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
mesh_terms: D000465:Algorithms; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging; D005260:Female; D019788:Fluorodeoxyglucose F18; D018628:Gene Dosage; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D016018:Least-Squares Analysis; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose