IC-P-001: Amyloid-associated alterations in metabolic connectivity patterns in ADNI participants (original) (raw)

Alzheimers & Dementia, 2013

Abstract

Background: While regional glucose hypometabolism is characteristic of Alzheimer’s disease (AD), this feature has been shown to be primarily associated with the ApoE4 genotype, rather than fibrillar b-amyloid, during the pre-clinical/early stages of the disease process. However, derangements of metabolic connectivity are intimately related to b-amyloid plaque burden. In order to assess the specific alterations in metabolic connectivity in early disease, we have performed a quantitative analysis of correlation patterns derived from FDG positron emission tomography (PET) images from ADNI subjects with different levels of cortical b-amyloid. Methods: [18F]florbetapir PET, [18F]FDG PET, and 3D T1-weighted MR images were obtained from ADNI-GO/-2 study subjects classified as cognitively normal or mild cognitive impairment (MCI). PET volumes were registered to a customized MRI template in MNI stereotaxic space, and standardized uptake value ratio (SUVR) images were generated and projected onto each subject’s cortical surface using Biospective’s fully-automated PIANO TM image processing software. The amyloid burden for each subject was determined from a composite region-of-interest (ROI) on [18F]florbetapir images, and subjects were categorized into Amyloid-Low (Ab L) and Amyloid-High (Ab H) groups. We generated vertexwise correlation strength maps across the entire cerebral cortex, controlling for ApoE4 genotype, and assessed the relative alterations in short-/long-range and intra-/interhemispheric metabolic connections in each group. Results: We observed statistically significant differences in short-/long-range and intra-/interhemispheric metabolic connections between the Ab L and Ab H groups in multiple cortical regions. For example, the entorhinal cortex showed greater reductions in interthan intra-hemispheric correlations (especially with the contralateral medial temporal lobe, precuneus, and posterior lateral temporal-parietal cortex) in the Ab H group. The angular gyrus demonstrated greater loss of longthan short-range metabolic correlations in the Ab H group.Conclusions:We have employed metabolic connectivity analysis to examine disruptions of the cortical correlation architecture as a function of b-amyloid burden. The aberrant metabolic connections observed in the Ab H group may be a consequence of variable spatio-temporal patterns of compensatory responses and/or cortical remodeling during the early stages of AD. The quantitative approach employed in this study may serve as a powerful, non-invasive imaging biomarker for early diagnosis/prognosis and objective evaluation of the efficacy of novel amyloid-lowering therapeutic agents.

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