Title The effect of ApoE epsilon 4 on longitudinal brain region-specific glucose metabolism in patients with mild cognitive impairment: a FDG-PET study
Authors Paranjpe, Manish D.
Ghen, Xueqi
Liu, Min
Paranjpe, Ishan
Leal, Jeffrey P.
Wang, Rongfu
Pomper, Martin G.
Wong, Dean F.
Benzinger, Tammie L. S.
Zhou, Yun
Affiliation Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Sch Med, Baltimore, MD 21287 USA
Peking Univ, Dept Nucl Med, Hosp 1, Beijing, Peoples R China
Icahn Sch Med Mt Sinai, New York, NY 10029 USA
Washington Univ, Mallinckrodt Inst Radiol, St Louis Sch Med, Campus Box 8225,510 S Kingshighway Blvd, St Louis, MO 63110 USA
Keywords Alzheimer's disease
Mild cognitive impairment
ApoE epsilon 4
FDG PET
Longitudinal
Partial volume correction
Issue Date 2019
Publisher NEUROIMAGE-CLINICAL
Abstract While the ApoE epsilon 4 allele is a known risk factor for mild cognitive impairment (MCI) and Alzheimer's disease, brain region specific effects remain elusive. In this study, we investigate whether the ApoE epsilon 4 allele exhibits brain region specific effects in longitudinal glucose uptake among patients with MCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed FDG PET images, MRIs, and demographic information were downloaded from the ADNI database. An iterative reblurred Van Cittertiteration method was used for partial volume correction (PVC) on all PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. Longitudinal changes in ROI FDG standardized uptake value ratio (SUVR) relative to cerebellum in 24 ApoE epsilon 4 carriers and 24 age-matched ApoE epsilon 4 non-carriers were measured for up to 84-months (median 72 months, SD = 11.2 months) and compared using a generalized linear mixed effects model controlling for gender, education, baseline age, and follow-up period. Additionally, voxelwise analysis was performed by implementing a paired t-test comparing matched baseline and 72 month FDG SUVR images in ApoE carriers and non-carriers separately. Results with PVC were compared with ones from non-PVC based analysis. After applying PVC, the superior fontal, parietal, lateral temporal, medial temporal, caudate, thalamus, and post-cingulate, and amygdala regions had greater longitudinal decreases in FDG uptake in ApoE epsilon 4 carriers with MCI compared to non-carriers with MCI. Similar forebrain and limbic clusters were found through voxelwise analysis. Compared to the PVC based analysis, fewer significant ApoE-associated regions and clusters were found in the non-PVC based PET analysis. Our findings suggest that the ApoE epsilon 4 genotype is associated with a longitudinal decline in glucose uptake in 8 forebrain and limbic brain regions in the context of MCI. In conclusion, this 84-months longitudinal FDG PET study demonstrates a novel ApoE epsilon 4-associated brain-region specific glucose metabolism pattern in patients with MCI. Partial volume correction improved FDG PET quantification.
URI http://hdl.handle.net/20.500.11897/551839
ISSN 2213-1582
DOI 10.1016/j.nicl.2019.101795
Indexed SCI(E)
Appears in Collections: 第一医院

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