@article{a621bdb587624bccb0f9e26d31be5491,
title = "Interregional causal influences of brain metabolic activity reveal the spread of aging effects during normal aging",
abstract = "During healthy brain aging, different brain regions show anatomical or functional declines at different rates, and some regions may show compensatory increases in functional activity. However, few studies have explored interregional influences of brain activity during the aging process. We proposed a causality analysis framework combining high dimensionality independent component analysis (ICA), Granger causality, and least absolute shrinkage and selection operator regression on longitudinal brain metabolic activity data measured by Fludeoxyglucose positron emission tomography (FDG–PET). We analyzed FDG–PET images from healthy old subjects, who were scanned for at least five sessions with an averaged intersession interval of 1 year. The longitudinal data were concatenated across subjects to form a time series, and the first-order autoregressive model was used to measure interregional causality among the independent sources of metabolic activity identified using ICA. Several independent sources with reduced metabolic activity in aging, including the anterior temporal lobe and orbital frontal cortex, demonstrated causal influences over many widespread brain regions. On the other hand, the influenced regions were more distributed, and had smaller age-related declines or even relatively increased metabolic activity. The current data demonstrated interregional spreads of aging on metabolic activity at the scale of a year, and have identified key brain regions in the aging process that have strong influences over other regions.",
keywords = "Granger causality, LASSO regression, aging, anterior temporal lobe, metabolic connectivity, orbitofrontal cortex",
author = "{The Alzheimer{\textquoteright}s Disease Neuroimaging Initiative} and Xin Di and Marie W{\"o}lfer and Mario Amend and Hans Wehrl and Ionescu, {Tudor M.} and Pichler, {Bernd J.} and Biswal, {Bharat B.}",
note = "Funding Information: The theoretical work and data analysis were funded by (U.S.) National Institute of Health grants: R01AT009829 and R01DA038895. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH‐12‐2‐0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol‐Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann‐La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio US; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development, LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( 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. Funding Information: information Northern California Institute for Research and Education; Foundation for the National Institutes of Health; Canadian Institutes of Health Research; Transition Therapeutics; Takeda Pharmaceutical Company; Servier; Piramal Imaging; Pfizer Inc.; Novartis Pharmaceuticals Corporation; Neurotrack Technologies; NeuroRx Research; Meso Scale Diagnostics, LLC.; Merck & Co., Inc.; Lundbeck; Lumosity; Johnson & Johnson Pharmaceutical Research & Development, LLC.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; IXICO Ltd.; GE Healthcare; Fujirebio US; Genentech, Inc.; F. Hoffmann-La Roche Ltd; EuroImmun; Eli Lilly and Company; Elan Pharmaceuticals, Inc.; Eisai Inc.; Cogstate; CereSpir, Inc.; Bristol-Myers Squibb Company; Biogen; BioClinica, Inc.; Araclon Biotech; Alzheimer's Drug Discovery Foundation; Alzheimer's Association; AbbVie; National Institute of Biomedical Imaging and Bioengineering; National Institute on Aging; Department of Defense, Grant/Award Number: W81XWH-12-2-0012; National Institutes of Health, Grant/Award Numbers: R01DA038895, R01AT009829, U01 AG024904; Alzheimer's Disease Neuroimaging InitiativeThe theoretical work and data analysis were funded by (U.S.) National Institute of Health grants: R01AT009829 and R01DA038895. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio US; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development, LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (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. Publisher Copyright: {\textcopyright} 2019 Wiley Periodicals, Inc.",
year = "2019",
month = nov,
day = "1",
doi = "10.1002/hbm.24728",
language = "English (US)",
volume = "40",
pages = "4657--4668",
journal = "Human Brain Mapping",
issn = "1065-9471",
publisher = "Wiley-Liss Inc.",
number = "16",
}