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The effect of ApoE ε4 on longitudinal brain region-specific glucose metabolism in patients with mild cognitive impairment: a FDG-PET study.
Neuroimage Clin. 2019; 22:101795.NC

Abstract

While the ApoE ε4 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 ε4 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 ε4 carriers and 24 age-matched ApoE ε4 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 ε4 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 ε4 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 ε4-associated brain-region specific glucose metabolism pattern in patients with MCI. Partial volume correction improved FDG PET quantification.

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Authors+Show Affiliations

Paranjpe MD
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
Chen X
Department of Nuclear Medicine, Peking University First Hospital, Beijing, China.
Liu M
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States; Department of Nuclear Medicine, Peking University First Hospital, Beijing, China.
Paranjpe I
Icahn School of Medicine at Mount Sinai, NY, New York, United States.
Leal JP
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
Wang R
Department of Nuclear Medicine, Peking University First Hospital, Beijing, China.
Pomper MG
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
Wong DF
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
Benzinger TLS
Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, United States.
Zhou Y
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States; Department of Nuclear Medicine, Peking University First Hospital, Beijing, China; Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, United States. Electronic address: yunzhou@wustl.edu.
Alzheimer's Disease Neuroimaging Initiative
No affiliation info available

MeSH

AgedAged, 80 and overApolipoprotein E4Apolipoproteins EBrainCognitive DysfunctionFemaleFluorodeoxyglucose F18GlucoseHumansLongitudinal StudiesMagnetic Resonance ImagingMaleMiddle AgedNeuroimagingPositron-Emission Tomography

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30991617

Citation

Paranjpe, Manish D., et al. "The Effect of ApoE Ε4 On Longitudinal Brain Region-specific Glucose Metabolism in Patients With Mild Cognitive Impairment: a FDG-PET Study." NeuroImage. Clinical, vol. 22, 2019, p. 101795.
Paranjpe MD, Chen X, Liu M, et al. The effect of ApoE ε4 on longitudinal brain region-specific glucose metabolism in patients with mild cognitive impairment: a FDG-PET study. Neuroimage Clin. 2019;22:101795.
Paranjpe, M. D., Chen, X., Liu, M., Paranjpe, I., Leal, J. P., Wang, R., Pomper, M. G., Wong, D. F., Benzinger, T. L. S., & Zhou, Y. (2019). The effect of ApoE ε4 on longitudinal brain region-specific glucose metabolism in patients with mild cognitive impairment: a FDG-PET study. NeuroImage. Clinical, 22, 101795. https://doi.org/10.1016/j.nicl.2019.101795
Paranjpe MD, et al. The Effect of ApoE Ε4 On Longitudinal Brain Region-specific Glucose Metabolism in Patients With Mild Cognitive Impairment: a FDG-PET Study. Neuroimage Clin. 2019;22:101795. PubMed PMID: 30991617.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of ApoE ε4 on longitudinal brain region-specific glucose metabolism in patients with mild cognitive impairment: a FDG-PET study. AU - Paranjpe,Manish D, AU - Chen,Xueqi, AU - Liu,Min, AU - Paranjpe,Ishan, AU - Leal,Jeffrey P, AU - Wang,Rongfu, AU - Pomper,Martin G, AU - Wong,Dean F, AU - Benzinger,Tammie L S, AU - Zhou,Yun, AU - ,, Y1 - 2019/03/28/ PY - 2018/07/30/received PY - 2019/03/12/revised PY - 2019/03/24/accepted PY - 2019/4/18/pubmed PY - 2020/1/22/medline PY - 2019/4/18/entrez KW - Alzheimer's disease KW - ApoE ε4 KW - FDG PET KW - Longitudinal KW - Mild cognitive impairment KW - Partial volume correction SP - 101795 EP - 101795 JF - NeuroImage. Clinical JO - Neuroimage Clin VL - 22 N2 - While the ApoE ε4 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 ε4 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 ε4 carriers and 24 age-matched ApoE ε4 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 ε4 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 ε4 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 ε4-associated brain-region specific glucose metabolism pattern in patients with MCI. Partial volume correction improved FDG PET quantification. SN - 2213-1582 UR - https://www.unboundmedicine.com/medline/citation/30991617/The_effect_of_ApoE_ε4_on_longitudinal_brain_region_specific_glucose_metabolism_in_patients_with_mild_cognitive_impairment:_a_FDG_PET_study_ DB - PRIME DP - Unbound Medicine ER -