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. 2012 May 1;60(4):2316-22.
doi: 10.1016/j.neuroimage.2012.02.005. Epub 2012 Feb 12.

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

Kewei Chen  1 , Napatkamon Ayutyanont, Jessica B S Langbaum, Adam S Fleisher, Cole Reschke, Wendy Lee, Xiaofen Liu, Gene E Alexander, Dan Bandy, Richard J Caselli, Eric M Reiman
Affiliations

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

Kewei Chen et al. Neuroimage. .

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.

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Figures

Figure 1
Figure 1
The PET-MRI paired covarying patterns. Left: FDG PET with cool color showing negative CMRgl correlation with APOE-ε4 gene dose. Right: the segmented MRI gray matter volume with cool color showing negative gray matter volume in correlation with APOE-ε4 gene dose. The orientation of the images displayed is neurological (left of the image is the left hemisphere).
Figure 2
Figure 2
Correlations between APOE4 gene dose and FDG PET-MRI MMPLS score. Left: training dataset, Right: testing dataset
See this image and copyright information in PMC

References

    1. Alexander GE, Chen K, Pietrini P, Rapoport SI, Reiman EM. Longitudinal PET Evaluation of Cerebral Metabolic Decline in Dementia: A Potential Outcome Measure in Alzheimer's Disease Treatment Studies. Am J Psychiatry. 2002;159:738–745. - PubMed
    1. Arnaiz E, Jelic V, Almkvist O, Wahlund LO, Winblad B, Valind S, Nordberg A. Impaired cerebral glucose metabolism and cognitive functioning predict deterioration in mild cognitive impairment. Neuroreport. 2001;12:851–855. - PubMed
    1. Ball MJ, Fisman M, Hachinski V, Blume W, Fox A, Kral VA, Kirshen AJ, Fox H, Merskey H. A new definition of Alzheimer's disease: a hippocampal dementia. Lancet. 1985;1:14–16. - PubMed
    1. Barta PE, Powers RE, Aylward EH, Chase GA, Harris GJ, Rabins PV, Tune LE, Pearlson GD. Quantitative MRI volume changes in late onset schizophrenia and Alzheimer's disease compared to normal controls. Psychiatry Res. 1997;68:65–75. - PubMed
    1. Basso M, Yang J, Warren L, Macavoy MG, Varma P, Bronen RA, van Dyck CH. Volumetry of amygdala and hippocampus and memory performance in Alzheimer's disease. Psychiatry Res. 2006;146:251–261. - PubMed

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