title: Intranetwork and internetwork connectivity in patients with Alzheimer disease and the association with cerebrospinal fluid biomarker levels.
abstract: BACKGROUND
  In the last decade, many studies have reported abnormal connectivity within the default mode network (DMN) in patients with Alzheimer disease. Few studies, however, have investigated other networks and their association with pathophysiological proteins obtained from cerebrospinal fluid (CSF).
  
  
  METHODS
  We performed 3 T imaging in patients with mild Alzheimer disease, patients with amnestic mild cognitive impairment (aMCI) and healthy controls, and we collected CSF samples from the patients with aMCI and mild Alzheimer disease. We analyzed 57 regions from 8 networks. Additionally, we performed correlation tests to investigate possible associations between the networks' functional connectivity and the protein levels obtained from the CSF of patients with aMCI and Alzheimer disease.
  
  
  RESULTS
  Our sample included 41 patients with Alzheimer disease, 35 with aMCI and 48 controls. We found that the main connectivity abnormalities in those with Alzheimer disease occurred between the DMN and task-positive networks: these patients presented not only a decreased anticorrelation between some regions, but also an inversion of the correlation signal (positive correlation instead of anticorrelation). Those with aMCI did not present statistically different connectivity from patients with Alzheimer disease or controls. Abnormal levels of CSF proteins were associated with functional disconnectivity between several regions in both the aMCI and mild Alzheimer disease groups, extending well beyond the DMN or temporal areas.
  
  
  CONCLUSIONS
  The presented data are cross-sectional in nature, and our findings are dependent on the choice of seed regions used.
  
  
  CONCLUSIONS
  We found that the main functional connectivity abnormalities occur between the DMN and task-positive networks and that the pathological levels of CSF biomarkers correlate with functional connectivity disruption in patients with Alzheimer disease.
authors.affiliation: From the Neuroimaging Laboratory, University of Campinas, São Paulo, Brazil (Weiler, de Campos, Teixeria, Casseb, Carletti-Cassani, Vicentini, Magalhães, Balthazar); and the Laboratory of Neuroscience, Department & Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil (Talib, Forlenza).
authors.forename: Marina
authors.initials: M
authors.lastname: Weiler
authors.affiliation: From the Neuroimaging Laboratory, University of Campinas, São Paulo, Brazil (Weiler, de Campos, Teixeria, Casseb, Carletti-Cassani, Vicentini, Magalhães, Balthazar); and the Laboratory of Neuroscience, Department & Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil (Talib, Forlenza).
authors.forename: Brunno Machado
authors.initials: BM
authors.lastname: de Campos
authors.affiliation: From the Neuroimaging Laboratory, University of Campinas, São Paulo, Brazil (Weiler, de Campos, Teixeria, Casseb, Carletti-Cassani, Vicentini, Magalhães, Balthazar); and the Laboratory of Neuroscience, Department & Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil (Talib, Forlenza).
authors.forename: Camila Vieira de Ligo
authors.initials: CVL
authors.lastname: Teixeira
authors.affiliation: From the Neuroimaging Laboratory, University of Campinas, São Paulo, Brazil (Weiler, de Campos, Teixeria, Casseb, Carletti-Cassani, Vicentini, Magalhães, Balthazar); and the Laboratory of Neuroscience, Department & Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil (Talib, Forlenza).
authors.forename: Raphael Fernandes
authors.initials: RF
authors.lastname: Casseb
authors.affiliation: From the Neuroimaging Laboratory, University of Campinas, São Paulo, Brazil (Weiler, de Campos, Teixeria, Casseb, Carletti-Cassani, Vicentini, Magalhães, Balthazar); and the Laboratory of Neuroscience, Department & Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil (Talib, Forlenza).
authors.forename: Ana Flávia Mac Knight
authors.initials: AFMK
authors.lastname: Carletti-Cassani
authors.affiliation: From the Neuroimaging Laboratory, University of Campinas, São Paulo, Brazil (Weiler, de Campos, Teixeria, Casseb, Carletti-Cassani, Vicentini, Magalhães, Balthazar); and the Laboratory of Neuroscience, Department & Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil (Talib, Forlenza).
authors.forename: Jéssica Elias
authors.initials: JE
authors.lastname: Vicentini
authors.affiliation: From the Neuroimaging Laboratory, University of Campinas, São Paulo, Brazil (Weiler, de Campos, Teixeria, Casseb, Carletti-Cassani, Vicentini, Magalhães, Balthazar); and the Laboratory of Neuroscience, Department & Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil (Talib, Forlenza).
authors.forename: Thamires Naela Cardoso
authors.initials: TNC
authors.lastname: Magalhães
authors.affiliation: From the Neuroimaging Laboratory, University of Campinas, São Paulo, Brazil (Weiler, de Campos, Teixeria, Casseb, Carletti-Cassani, Vicentini, Magalhães, Balthazar); and the Laboratory of Neuroscience, Department & Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil (Talib, Forlenza).
authors.forename: Leda Leme
authors.initials: LL
authors.lastname: Talib
authors.affiliation: From the Neuroimaging Laboratory, University of Campinas, São Paulo, Brazil (Weiler, de Campos, Teixeria, Casseb, Carletti-Cassani, Vicentini, Magalhães, Balthazar); and the Laboratory of Neuroscience, Department & Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil (Talib, Forlenza).
authors.forename: Orestes Vicente
authors.initials: OV
authors.lastname: Forlenza
authors.affiliation: From the Neuroimaging Laboratory, University of Campinas, São Paulo, Brazil (Weiler, de Campos, Teixeria, Casseb, Carletti-Cassani, Vicentini, Magalhães, Balthazar); and the Laboratory of Neuroscience, Department & Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil (Talib, Forlenza).
authors.forename: Marcio Luiz Figueredo
authors.initials: MLF
authors.lastname: Balthazar
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000503:physiopathology*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001931:Brain Mapping; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D009483:Neuropsychological Tests; D012146:Rest
chemical_list: D015415:Biomarkers