title: Predicting the transition from normal aging to Alzheimer's disease: A statistical mechanistic evaluation of FDG-PET data.
abstract: The assessment of the degree of order of brain metabolism by means of a statistical mechanistic approach applied to FDG-PET, allowed us to characterize healthy subjects as well as patients with mild cognitive impairment and Alzheimer's Disease (AD). The intensity signals from 24 volumes of interest were submitted to principal component analysis (PCA) giving rise to a major first principal component whose eigenvalue was a reliable cumulative index of order. This index linearly decreased from 77 to 44% going from normal aging to AD patients with intermediate conditions between these values (r=0.96, p<0.001). Bootstrap analysis confirmed the statistical significance of the results. The progressive detachment of different brain regions from the first component was assessed, allowing for a purely data driven reconstruction of already known maximally affected areas. We demonstrated for the first time the reliability of a single global index of order in discriminating groups of cognitively impaired patients with different clinical outcome. The second relevant finding was the identification of clusters of regions relevant to AD pathology progressively separating from the first principal component through different stages of cognitive impairment, including patients cognitively impaired but not converted to AD. This paved the way to the quantitative assessment of the functional networking status in individual patients.
authors.affiliation: Institute of Cognitive Sciences and Technologies, CNR, Rome, Italy; Department of Nuclear Medicine, Karolinska Hospital Stockholm, Sweden. Electronic address: marco.pagani@istc.cnr.it.
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: Istituto Nazionale di Fisica Nucleare, Sezione di Genova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Chincarini
authors.affiliation: Department of Nuclear Medicine, Department of Health Science (DISSAL), University of Genoa and IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Morbelli
authors.affiliation: Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa and IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Brugnolo
authors.affiliation: Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa and IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Arnaldi
authors.affiliation: Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa and IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Picco
authors.affiliation: Department of Nuclear Medicine, Department of Health Science (DISSAL), University of Genoa and IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bauckneht
authors.affiliation: Department of Nuclear Medicine, Department of Health Science (DISSAL), University of Genoa and IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Ambra
authors.initials: A
authors.lastname: Buschiazzo
authors.affiliation: Department of Nuclear Medicine, Department of Health Science (DISSAL), University of Genoa and IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Gianmario
authors.initials: G
authors.lastname: Sambuceti
authors.affiliation: Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa and IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Nobili
mesh_terms: D000368:Aged; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000378:metabolism*; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D018450:Disease Progression; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D015233:Models, Statistical; D049268:Positron-Emission Tomography; D011379:Prognosis; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: Alzheimer's disease; Degree of order; FDG-Pet; Mild cognitive impairment; Normal aging; Principal component analysis