title: Progressive Disintegration of Brain Networking from Normal Aging to Alzheimer Disease: Analysis of Independent Components of18F-FDG PET Data.
abstract: Brain connectivity has been assessed in several neurodegenerative disorders investigating the mutual correlations between predetermined regions or nodes. Selective breakdown of brain networks during progression from normal aging to Alzheimer disease dementia (AD) has also been observed.Methods:We implemented independent-component analysis of18F-FDG PET data in 5 groups of subjects with cognitive states ranging from normal aging to AD-including mild cognitive impairment (MCI) not converting or converting to AD-to disclose the spatial distribution of the independent components in each cognitive state and their accuracy in discriminating the groups.Results:We could identify spatially distinct independent components in each group, with generation of local circuits increasing proportionally to the severity of the disease. AD-specific independent components first appeared in the late-MCI stage and could discriminate converting MCI and AD from nonconverting MCI with an accuracy of 83.5%. Progressive disintegration of the intrinsic networks from normal aging to MCI to AD was inversely proportional to the conversion time.Conclusion:Independent-component analysis of18F-FDG PET data showed a gradual disruption of functional brain connectivity with progression of cognitive decline in AD. This information might be useful as a prognostic aid for individual patients and as a surrogate biomarker in intervention trials.
authors.affiliation: Institute of Cognitive Sciences and Technologies, CNR, Rome, Italy marco.pagani@istc.cnr.it.|Department of Nuclear Medicine, Karolinska Hospital, Stockholm, Sweden.
authors.forename: Marco
authors.initials: M
authors.lastname: Pagani
authors.affiliation: Environment and Health Department, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giuliani
authors.affiliation: Department of Hospital Physics, Karolinska Hospital, Stockholm, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Öberg
authors.affiliation: Institute of Molecular Bioimaging and Physiology, CNR, Genoa, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: De Carli
authors.affiliation: Departments of Nuclear Medicine and Health Science, University of Genoa, and IRCCS AOU San Martino-IST, Genoa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Morbelli
authors.affiliation: Clinical Neurology, Department of Neuroscience, University of Genoa, and IRCCS AOU San Martino-IST, Genoa, Italy.|Clinical Psychology, IRCCS AOU San Martino-IST, Genoa, Italy; and.
authors.forename: Nicola
authors.initials: N
authors.lastname: Girtler
authors.affiliation: Clinical Neurology, Department of Neuroscience, University of Genoa, and IRCCS AOU San Martino-IST, Genoa, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Arnaldi
authors.affiliation: Clinical Neurology, Department of Neuroscience, University of Genoa, and IRCCS AOU San Martino-IST, Genoa, Italy.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Accardo
authors.affiliation: Departments of Nuclear Medicine and Health Science, University of Genoa, and IRCCS AOU San Martino-IST, Genoa, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bauckneht
authors.affiliation: Departments of Nuclear Medicine and Health Science, University of Genoa, and IRCCS AOU San Martino-IST, Genoa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bongioanni
authors.affiliation: National Institute of Nuclear Physics, Genoa, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Chincarini
authors.affiliation: Departments of Nuclear Medicine and Health Science, University of Genoa, and IRCCS AOU San Martino-IST, Genoa, Italy.
authors.forename: Gianmario
authors.initials: G
authors.lastname: Sambuceti
authors.affiliation: Department of Hospital Physics, Karolinska Hospital, Stockholm, Sweden.
authors.forename: Cathrine
authors.initials: C
authors.lastname: Jonsson
authors.affiliation: Clinical Neurology, Department of Neuroscience, University of Genoa, and IRCCS AOU San Martino-IST, Genoa, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Nobili
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000503:physiopathology*; D063132:Connectome / Q000379:methods*; D018450:Disease Progression; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D008875:Middle Aged; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000503:physiopathology*; D049268:Positron-Emission Tomography / Q000379:methods; D025341:Principal Component Analysis; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: 18F-FDG PET; Alzheimer disease; independent-component analysis; mild cognitive impairment; normal aging