Effects of Alzheimer and Lewy Body Disease Pathologies on Brain Metabolism

the Alzheimer's Disease Neuroimaging Initiative

doi:10.1002/ana.26355

Effects of Alzheimer and Lewy Body Disease Pathologies on Brain Metabolism

the Alzheimer's Disease Neuroimaging Initiative

Department of Neurology

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

Objective: This study aimed to determine the pattern of ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) related to postmortem Lewy body disease (LBD) pathology in clinical Alzheimer disease (AD). Methods: FDG-PET scans were analyzed in 62 autopsy-confirmed patients and 110 controls in the Alzheimer's Disease Neuroimaging Initiative. Based on neuropathologic evaluations on Braak stage for neurofibrillary tangle, Consortium to Establish a Registry for AD score for neuritic plaque, and Lewy-related pathology, subjects were classified into AD(−)/LBD(−), AD(−)/LBD(+), AD(+)/LBD(−), and AD(+)/LBD(+) groups. The association between postmortem LBD and AD pathologies and antemortem brain metabolism was evaluated. Results: AD and LBD pathologies had significant interaction effects to decrease metabolism in the cerebellar vermis, bilateral caudate, putamen, basal frontal cortex, and anterior cingulate cortex in addition to the left side of the entorhinal cortex and amygdala, and significant interaction effects to increase metabolism in the bilateral parietal and occipital cortices. LBD pathology was associated with hypermetabolism in the cerebellar vermis, bilateral putamen, anterior cingulate cortex, and basal frontal cortex, corresponding to the Lewy body-related hypermetabolic patterns. AD pathology was associated with hypometabolism in the bilateral hippocampus, entorhinal cortex, and posterior cingulate cortex regardless of LBD pathology, whereas LBD pathology was associated with hypermetabolism in the bilateral putamen and anterior cingulate cortex regardless of AD pathology. Interpretation: Postmortem LBD and AD pathologies had significant interaction effects on the antemortem brain metabolism in clinical AD patients. Specific metabolic patterns related to AD and LBD pathologies could be elucidated when simultaneously considering the two pathologies. ANN NEUROL 2022;91:853–863.

Original language	English
Pages (from-to)	853-863
Number of pages	11
Journal	Annals of Neurology
Volume	91
Issue number	6
DOIs	https://doi.org/10.1002/ana.26355
Publication status	Published - 2022 Jun

Bibliographical note

Funding Information:
Data collection and sharing for this project were funded by the ADNI (NIH grant U01 AG024904) and Department of Defense ADNI (DOD award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following groups: AbbVie, Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Araclon Biotech, BioClinica, Biogen, Bristol-Myers Squibb Company, CereSpir, Cogstate, Eisai, Elan Pharmaceuticals, Eli Lilly and Company, EuroImmun, F. Hoffmann-La Roche and its affiliated company Genentech, Fujirebio, GE Healthcare, IXICO, Janssen Alzheimer Immunotherapy Research & Development, Johnson & Johnson Pharmaceutical Research & Development, Lumosity, Lundbeck, Merck & Co, Meso Scale Diagnostics, NeuroRx Research, Neurotrack Technologies, Novartis Pharmaceuticals Corporation, Pfizer, Piramal Imaging, Servier, Takeda Pharmaceutical Company, and Transition Therapeutics. The Canadian Institutes of Health Research provided funding to support the ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org/). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea (grant number HU20C0511020021) and by the National Research Foundation of Korea grant funded by the Korea government (MSIT; 2022R1C1C2011227). We thank all of the participants in this study.

Funding Information:
Data collection and sharing for this project were funded by the ADNI (NIH grant U01 AG024904) and Department of Defense ADNI (DOD award number W81XWH‐12‐2‐0012). ADNI is funded by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following groups: AbbVie, Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Araclon Biotech, BioClinica, Biogen, Bristol‐Myers Squibb Company, CereSpir, Cogstate, Eisai, Elan Pharmaceuticals, Eli Lilly and Company, EuroImmun, F. Hoffmann‐La Roche and its affiliated company Genentech, Fujirebio, GE Healthcare, IXICO, Janssen Alzheimer Immunotherapy Research & Development, Johnson & Johnson Pharmaceutical Research & Development, Lumosity, Lundbeck, Merck & Co, Meso Scale Diagnostics, NeuroRx Research, Neurotrack Technologies, Novartis Pharmaceuticals Corporation, Pfizer, Piramal Imaging, Servier, Takeda Pharmaceutical Company, and Transition Therapeutics. The Canadian Institutes of Health Research provided funding to support the ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( http://www.fnih.org/ ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea (grant number HU20C0511020021) and by the National Research Foundation of Korea grant funded by the Korea government (MSIT; 2022R1C1C2011227). We thank all of the participants in this study.

Publisher Copyright:
© 2022 American Neurological Association.

All Science Journal Classification (ASJC) codes

Neurology
Clinical Neurology

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10.1002/ana.26355

Cite this

@article{b73580b3f3bd4af9a285116f73463fce,

title = "Effects of Alzheimer and Lewy Body Disease Pathologies on Brain Metabolism",

abstract = "Objective: This study aimed to determine the pattern of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) related to postmortem Lewy body disease (LBD) pathology in clinical Alzheimer disease (AD). Methods: FDG-PET scans were analyzed in 62 autopsy-confirmed patients and 110 controls in the Alzheimer's Disease Neuroimaging Initiative. Based on neuropathologic evaluations on Braak stage for neurofibrillary tangle, Consortium to Establish a Registry for AD score for neuritic plaque, and Lewy-related pathology, subjects were classified into AD(−)/LBD(−), AD(−)/LBD(+), AD(+)/LBD(−), and AD(+)/LBD(+) groups. The association between postmortem LBD and AD pathologies and antemortem brain metabolism was evaluated. Results: AD and LBD pathologies had significant interaction effects to decrease metabolism in the cerebellar vermis, bilateral caudate, putamen, basal frontal cortex, and anterior cingulate cortex in addition to the left side of the entorhinal cortex and amygdala, and significant interaction effects to increase metabolism in the bilateral parietal and occipital cortices. LBD pathology was associated with hypermetabolism in the cerebellar vermis, bilateral putamen, anterior cingulate cortex, and basal frontal cortex, corresponding to the Lewy body-related hypermetabolic patterns. AD pathology was associated with hypometabolism in the bilateral hippocampus, entorhinal cortex, and posterior cingulate cortex regardless of LBD pathology, whereas LBD pathology was associated with hypermetabolism in the bilateral putamen and anterior cingulate cortex regardless of AD pathology. Interpretation: Postmortem LBD and AD pathologies had significant interaction effects on the antemortem brain metabolism in clinical AD patients. Specific metabolic patterns related to AD and LBD pathologies could be elucidated when simultaneously considering the two pathologies. ANN NEUROL 2022;91:853–863.",

author = "{the Alzheimer's Disease Neuroimaging Initiative} and Lee, {Young gun} and Seun Jeon and Mincheol Park and Kang, {Sung Woo} and Yoon, {So Hoon} and Kyoungwon Baik and Lee, {Phil Hyu} and Sohn, {Young Ho} and Ye, {Byoung Seok}",

note = "Funding Information: Data collection and sharing for this project were funded by the ADNI (NIH grant U01 AG024904) and Department of Defense ADNI (DOD award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following groups: AbbVie, Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Araclon Biotech, BioClinica, Biogen, Bristol-Myers Squibb Company, CereSpir, Cogstate, Eisai, Elan Pharmaceuticals, Eli Lilly and Company, EuroImmun, F. Hoffmann-La Roche and its affiliated company Genentech, Fujirebio, GE Healthcare, IXICO, Janssen Alzheimer Immunotherapy Research & Development, Johnson & Johnson Pharmaceutical Research & Development, Lumosity, Lundbeck, Merck & Co, Meso Scale Diagnostics, NeuroRx Research, Neurotrack Technologies, Novartis Pharmaceuticals Corporation, Pfizer, Piramal Imaging, Servier, Takeda Pharmaceutical Company, and Transition Therapeutics. The Canadian Institutes of Health Research provided funding to support the ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org/). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea (grant number HU20C0511020021) and by the National Research Foundation of Korea grant funded by the Korea government (MSIT; 2022R1C1C2011227). We thank all of the participants in this study. Funding Information: Data collection and sharing for this project were funded by the ADNI (NIH grant U01 AG024904) and Department of Defense ADNI (DOD award number W81XWH‐12‐2‐0012). ADNI is funded by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following groups: AbbVie, Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Araclon Biotech, BioClinica, Biogen, Bristol‐Myers Squibb Company, CereSpir, Cogstate, Eisai, Elan Pharmaceuticals, Eli Lilly and Company, EuroImmun, F. Hoffmann‐La Roche and its affiliated company Genentech, Fujirebio, GE Healthcare, IXICO, Janssen Alzheimer Immunotherapy Research & Development, Johnson & Johnson Pharmaceutical Research & Development, Lumosity, Lundbeck, Merck & Co, Meso Scale Diagnostics, NeuroRx Research, Neurotrack Technologies, Novartis Pharmaceuticals Corporation, Pfizer, Piramal Imaging, Servier, Takeda Pharmaceutical Company, and Transition Therapeutics. The Canadian Institutes of Health Research provided funding to support the ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( http://www.fnih.org/ ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea (grant number HU20C0511020021) and by the National Research Foundation of Korea grant funded by the Korea government (MSIT; 2022R1C1C2011227). We thank all of the participants in this study. Publisher Copyright: {\textcopyright} 2022 American Neurological Association.",

year = "2022",

month = jun,

doi = "10.1002/ana.26355",

language = "English",

volume = "91",

pages = "853--863",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "John Wiley and Sons Inc.",

number = "6",

}

TY - JOUR

T1 - Effects of Alzheimer and Lewy Body Disease Pathologies on Brain Metabolism

AU - the Alzheimer's Disease Neuroimaging Initiative

AU - Lee, Young gun

AU - Jeon, Seun

AU - Park, Mincheol

AU - Kang, Sung Woo

AU - Yoon, So Hoon

AU - Baik, Kyoungwon

AU - Lee, Phil Hyu

AU - Sohn, Young Ho

AU - Ye, Byoung Seok

N1 - Funding Information: Data collection and sharing for this project were funded by the ADNI (NIH grant U01 AG024904) and Department of Defense ADNI (DOD award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following groups: AbbVie, Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Araclon Biotech, BioClinica, Biogen, Bristol-Myers Squibb Company, CereSpir, Cogstate, Eisai, Elan Pharmaceuticals, Eli Lilly and Company, EuroImmun, F. Hoffmann-La Roche and its affiliated company Genentech, Fujirebio, GE Healthcare, IXICO, Janssen Alzheimer Immunotherapy Research & Development, Johnson & Johnson Pharmaceutical Research & Development, Lumosity, Lundbeck, Merck & Co, Meso Scale Diagnostics, NeuroRx Research, Neurotrack Technologies, Novartis Pharmaceuticals Corporation, Pfizer, Piramal Imaging, Servier, Takeda Pharmaceutical Company, and Transition Therapeutics. The Canadian Institutes of Health Research provided funding to support the ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org/). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea (grant number HU20C0511020021) and by the National Research Foundation of Korea grant funded by the Korea government (MSIT; 2022R1C1C2011227). We thank all of the participants in this study. Funding Information: Data collection and sharing for this project were funded by the ADNI (NIH grant U01 AG024904) and Department of Defense ADNI (DOD award number W81XWH‐12‐2‐0012). ADNI is funded by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following groups: AbbVie, Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Araclon Biotech, BioClinica, Biogen, Bristol‐Myers Squibb Company, CereSpir, Cogstate, Eisai, Elan Pharmaceuticals, Eli Lilly and Company, EuroImmun, F. Hoffmann‐La Roche and its affiliated company Genentech, Fujirebio, GE Healthcare, IXICO, Janssen Alzheimer Immunotherapy Research & Development, Johnson & Johnson Pharmaceutical Research & Development, Lumosity, Lundbeck, Merck & Co, Meso Scale Diagnostics, NeuroRx Research, Neurotrack Technologies, Novartis Pharmaceuticals Corporation, Pfizer, Piramal Imaging, Servier, Takeda Pharmaceutical Company, and Transition Therapeutics. The Canadian Institutes of Health Research provided funding to support the ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( http://www.fnih.org/ ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea (grant number HU20C0511020021) and by the National Research Foundation of Korea grant funded by the Korea government (MSIT; 2022R1C1C2011227). We thank all of the participants in this study. Publisher Copyright: © 2022 American Neurological Association.

PY - 2022/6

Y1 - 2022/6

N2 - Objective: This study aimed to determine the pattern of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) related to postmortem Lewy body disease (LBD) pathology in clinical Alzheimer disease (AD). Methods: FDG-PET scans were analyzed in 62 autopsy-confirmed patients and 110 controls in the Alzheimer's Disease Neuroimaging Initiative. Based on neuropathologic evaluations on Braak stage for neurofibrillary tangle, Consortium to Establish a Registry for AD score for neuritic plaque, and Lewy-related pathology, subjects were classified into AD(−)/LBD(−), AD(−)/LBD(+), AD(+)/LBD(−), and AD(+)/LBD(+) groups. The association between postmortem LBD and AD pathologies and antemortem brain metabolism was evaluated. Results: AD and LBD pathologies had significant interaction effects to decrease metabolism in the cerebellar vermis, bilateral caudate, putamen, basal frontal cortex, and anterior cingulate cortex in addition to the left side of the entorhinal cortex and amygdala, and significant interaction effects to increase metabolism in the bilateral parietal and occipital cortices. LBD pathology was associated with hypermetabolism in the cerebellar vermis, bilateral putamen, anterior cingulate cortex, and basal frontal cortex, corresponding to the Lewy body-related hypermetabolic patterns. AD pathology was associated with hypometabolism in the bilateral hippocampus, entorhinal cortex, and posterior cingulate cortex regardless of LBD pathology, whereas LBD pathology was associated with hypermetabolism in the bilateral putamen and anterior cingulate cortex regardless of AD pathology. Interpretation: Postmortem LBD and AD pathologies had significant interaction effects on the antemortem brain metabolism in clinical AD patients. Specific metabolic patterns related to AD and LBD pathologies could be elucidated when simultaneously considering the two pathologies. ANN NEUROL 2022;91:853–863.

AB - Objective: This study aimed to determine the pattern of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) related to postmortem Lewy body disease (LBD) pathology in clinical Alzheimer disease (AD). Methods: FDG-PET scans were analyzed in 62 autopsy-confirmed patients and 110 controls in the Alzheimer's Disease Neuroimaging Initiative. Based on neuropathologic evaluations on Braak stage for neurofibrillary tangle, Consortium to Establish a Registry for AD score for neuritic plaque, and Lewy-related pathology, subjects were classified into AD(−)/LBD(−), AD(−)/LBD(+), AD(+)/LBD(−), and AD(+)/LBD(+) groups. The association between postmortem LBD and AD pathologies and antemortem brain metabolism was evaluated. Results: AD and LBD pathologies had significant interaction effects to decrease metabolism in the cerebellar vermis, bilateral caudate, putamen, basal frontal cortex, and anterior cingulate cortex in addition to the left side of the entorhinal cortex and amygdala, and significant interaction effects to increase metabolism in the bilateral parietal and occipital cortices. LBD pathology was associated with hypermetabolism in the cerebellar vermis, bilateral putamen, anterior cingulate cortex, and basal frontal cortex, corresponding to the Lewy body-related hypermetabolic patterns. AD pathology was associated with hypometabolism in the bilateral hippocampus, entorhinal cortex, and posterior cingulate cortex regardless of LBD pathology, whereas LBD pathology was associated with hypermetabolism in the bilateral putamen and anterior cingulate cortex regardless of AD pathology. Interpretation: Postmortem LBD and AD pathologies had significant interaction effects on the antemortem brain metabolism in clinical AD patients. Specific metabolic patterns related to AD and LBD pathologies could be elucidated when simultaneously considering the two pathologies. ANN NEUROL 2022;91:853–863.

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Effects of Alzheimer and Lewy Body Disease Pathologies on Brain Metabolism

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